Richard Noll
email: richard.noll@desales.edu

Kraepelin's 'lost biological psychiatry'? Autointoxication, organotherapy and surgery for dementia praecox

Keywords: autointoxication theory, dementia praecox, Emil Kraepelin, focal infection theory, history, organotherapy, psychiatry, surgical treatments, USA

Kraepelin believed that a chronic metabolic autointoxication, perhaps arising from the sex glands, eventually caused chemical damage to the brain and led to the symptoms of dementia praecox. The evolution of Kraepelin's autointoxication theory of dementia praecox is traced through the 5th to 8th (1895 to 1913) editions of his textbook, Psychiatrie. The historical context of autointoxication theory in medicine is explored in depth to enable the understanding of Kraepelin's aetiological assumption and his application of a rational treatment based on it -organotherapy. A brief account of the North American reception of Kraepelin's concept of dementia praecox, its autotoxic basis, and the preferred American style of rational treatment -surgeryconcludes the discussion.

of large numbers of cases. Of the multitude of mental illnesses and their subtypes identifi ed and modifi ed by Kraepelin over the course of his career, it is fair to say that until recently only dementia praecox was routinely invoked by historians of psychiatry as the paramount exemplum of how Kraepelin put theory into practice. Scholars are now devoting increasing attention to Kraepelin's changing clinical taxonomy of his other major insanity, manicdepressive illness [START_REF] Angst | Historical aspects of the dichotomy between manic-depressive disorders and schizophrenia[END_REF][START_REF] Marneros | Bipolar disorders beyond major depression and euphoric mania[END_REF].

Viewing Kraepelin's dementia praecox through the lens of the development of his psychopathological method has placed a deserved emphasis on its changing diagnostic criteria, courses and outcomes throughout Kraepelin's career. The multiple changes Kraepelin made in his own definition of the forms and courses of dementia praecox in the last thirty years of his life were matched by equally creative contributions from Eugen Bleuler (1857Bleuler ( -1939) ) and others, leading to the conclusion of some scholars (which I happen to share) that dementia praecox or schizophrenia 'is not the result of one defi nition and one object of inquiry successively studied by various psychiatric groups but a patchwork made out of clinical features plucked from different defi nitions' (Berrios, Luque and Villagran, 2003: 111). Despite the value of such conceptual histories, these discussions -of which there are many -have obscured an interesting but neglected aspect of Kraepelin's medical cognition: his speculation as to the aetiology of dementia praecox.

Kraepelin fi rst proposed the term dementia praecox to identify a psychotic disorder in the 1893 fourth edition of his textbook, Psychiatrie, providing a fuller (indeed, the fi rst) clinical description in the fi fth edition of 1896. He may have borrowed the term from Arnold Pick (1851Pick ( -1924)), Professor of Psychiatry at the German university in Prague, who had used the Latin form 'dementia praecox' to label a hebephrenia-like psychotic disorder just a few years earlier [START_REF] Pick | Ueber primäre chronische Demenz (so. Dementia praecox) im jugendlichen Alter[END_REF]. Until 1899 dementia praecox was essentially identical with the psychotic disorder Ewald Hecker (1843-1909) had identifi ed decades earlier as 'hebephrenia' [START_REF] Hecker | Die Hebephrenie[END_REF]. However, it was through (in part) the continuing analysis of his vast collection of data cards on individual patients that he was able to introduce, in the 1899 sixth edition of his textbook, the now classic clinical description of dementia praecox as the heterogeneous disease comprised of at least three subtypes (the hebephrenic, catatonic and paranoid), each with its own identifi able clinical psychopathology. Kraepelin devoted very few pages to the issue of aetiology in the various editions of his textbook and focused instead on an increasingly complex picture of its clinical presentation, expanding the number of essential forms or subtypes from the classic three of 1899 to at least ten by the eighth edition of Psychiatrie in 1913.

Kraepelin, however, was not completely silent on the issue of the causes of dementia praecox. Heredity, of course, was acknowledged as an important aetiological factor. However, in my opinion, the importance of heredity as the singular cause of dementia praecox has been grossly overestimated by some scholars. These scholars tend to place Kraepelin's hereditarian views within the context of degeneration theory, which he did in fact believe to be true [START_REF] Engstrom | Emil Kraepelin's 'Self-Assessment': clinical autobiography in historical context (Classic Text No. 49)[END_REF]. This has led to a monocausal misinterpretation of Kraepelin's views. His views of heredity were more nuanced, more probabilistic and signifi cantly more congruent with the assumptions of the behavioural genetics of today than with the tenets of nineteenth-century degeneration theory. His statements on the role of heredity in the aetiology of dementia praecox attest to this.

What is missing in the current scholarship on Kraepelin is a discussion of a key component of his medical cognition: the belief that dementia praecox was due to an endogenous process of chronic autointoxication which led to a 'self-poisoning (Selbstvergiftung)' of the body and, eventually, its brain. Scholars who continue to cite only the fatalism of heredity or degeneration keep missing the point: in Kraepelin's view, the true origin of dementia praecox was not to be found in the cells of the central nervous system, nor (entirely) in the shadowy ancestral chambers of the germ plasm, but active and alive elsewhere in the present body. Furthermore, if dementia praecox was directly caused by proximal rather than distal biological processes, it was a potentially preventable and treatable disease. Kraepelin held out no hope for complete cures, but, at least for some time, he believed that the prevention of dementia praecox and the development of rational therapies were possible if only the mysterious mechanisms of the self-poisoning process could be discovered.

Historians of psychiatry continue to ignore the subtleties of the early twentieth-century discussions on the aetiological heterogeneity of dementia praecox and its successor, schizophrenia. Many biological psychiatrists of Kraepelin's era, like the biological psychiatrists of today who research schizophrenia [START_REF] Hirsch | Schizophrenia[END_REF], understood that the disease could not be explained by heredity or genetics alone. To fully understand Kraepelin's view of dementia praecox we must fi rst understand the context of the medical world in which he lived and worked, an era energized by the 'laboratory revolution in medicine' (Cunningham and Williams, 1992) and the resulting rise of bacteriology in the 1870s, endocrinology in the 1890s and serology and immunology in the fi rst decade of the 1900s. All these new medical sciences played a role in framing the various autointoxication theories of Kraepelin's era -and by extension, what I refer to as the 'lost biological psychiatry' of a century ago.

The two variants of autointoxication theory

Among the learned elites of medicine, if not among the majority of practising physicians, by 1880 the germ theory of disease and the new medical science of bacteriology offered a novel and potentially fruitful paradigm for comprehending illness. Following the replicable laboratory demonstration that bacteria or microbes were involved in processes such as putrefaction, fermentation and infection, it was a natural cognitive leap to hypothesize that they were involved in the aetiology and pathophysiology of many -if not most -diseases. The applicability of the germ theory of disease to the study of the insanities was suggested as early as 1874 in the American Journal of Insanity by Theodore Deecke, the pathologist of the New York State Lunatic Asylum [START_REF] Deecke | On the germ-theory of disease[END_REF]. By the late 1880s it was argued that diseases were not caused by the bacterial organisms acting directly, but instead by the toxins they produced. Poisonous ptomaines (the products of proteins formed in putrefaction) or 'toxalbumins' were formed that could be circulated through the body's bloodstream and produce a wide variety of diseases affecting almost every organ. In the original, classical form of autointoxication theory, the intestines were most often cited as the locus of this systemic selfpoisoning process, with the kidneys and liver assuming lesser importance in theoretical speculation. The term intestinal or gastrointestinal autointoxication was most often used in the literature of that era. In later years, this variant of autointoxication theory would be termed focal infection or focal sepsis [START_REF] Billings | Focal infection: The Lane Medical Lectures[END_REF]. Beginning in the year 1900 the teeth, gums and tonsils were most often cited as the original source of pathogens that would spread throughout the body and infect various organs and tissues [START_REF] Scull | Madhouse: A Tragic Tale of Megalomania and Modern Medicine[END_REF].

A second variant of autointoxication theory arose in the 1890s when endocrinology began to emerge out of physiology as a distinct discipline of clinical and research medicine. The French physiologist and neurologist C.-E. Brown-Sequard (1817-94) and his assistant Arsene d'Arsonval published an article in April 1891 in which it was fi rst proposed that disease could result from the lack of production of 'internal secretions' in animal tissues, and this newly posited pathogenic mechanism was incorporated into autointoxication theory [START_REF] Borrell | Organotherapy, British physiology, and the discovery of internal secretions[END_REF]. The work of British physiologist George Redmayne Murray (1865Murray ( -1939)), who discovered the cure of myxoedema by subcutaneous injection of thyroid extract in 1891, particularly intrigued Kraepelin. By 1900 the over-or under-production of 'internal secretions' in the glands of the body were posited as the cause of a wide variety of diseases, both physical and mental. It was this interstitial or metabolic autointoxication theory that infl uenced most biological psychiatrists in the fi rst three decades of the twentieth century.

Gastrointestinal autointoxication

The disease theory of autointoxication fi rst appeared in the German medical literature. Hermann Senator (1834Senator ( -1911)), a clinical professor at Berlin University, had speculated as early as 1868 that 'self-infection' arising in the intestines could be a source of disease elsewhere in the body [START_REF] Senator | Ueber ein Fall von Hydrothionamie und über Selbstinfektion durch abnorme Verdauungsvorgänge[END_REF]. Later he argued that mental disturbances could be caused by to this process, claiming that the acute delirium of diabetic coma may have its origin in 'Selbstinfektion' [START_REF] Senator | Ueber Selbstinfektion durch abnorme Zersetzungsvorgänge und ein dadurch bedingtes (dyskrasisches) Coma (Kussmaulscher Symptomenkomplex des "diabetischen Coma[END_REF].

However, it was the work of French physicians that fuelled the rapid expansion of this theory to all categories of disease, including mental disorders. Autointoxication theory rose to international prominence in medicine after the 1887 publication of Leçons sur les auto-intoxications dans les maladies by Charles Jacques Bouchard (1837Bouchard ( -1915)), an early student of Charcot and an eminent Professor of Pathology at the University of Paris [START_REF] Bouchard | Leçons sur les auto-intoxications dans les maladies[END_REF][START_REF] Conrepois | The clinician, germs and infectious diseases: the example of Charles Bouchard in Paris[END_REF]. For both Senator and Bouchard -the founders of autointoxication theory -the disease-causing poisons were the products of putrefactive processes in the intestines. Although a normal part of the digestive process, under certain conditions (such as faecal stasis) the overproduction of these toxins could not be fi ltered by the liver or kidneys and, as they entered other organs, disease would result. Bouchard's vision of the inner life of the human body is dramatic:

I have said that the organism, in its normal, as in its pathological state, is a receptacle and a laboratory of poisons … Man is in this way constantly living under the chance of being poisoned; he is always working towards his own destruction; he makes continual attempts at suicide by intoxication. (Bouchard, 1894: 14) It was not until 1893, however, that we fi nd the fi rst indications that autointoxication theory was being seriously discussed as a possible aetiology for mental disorders. On 1 August of that year, at the Fourth Session of the French Congress of Psychological Medicine held in La Rochelle, 'Rapporteurs' Francois-Andre Chevalier-Lavaure, a physician from Aix-en-Provence, and Emmanuel Regis, a physician from Bordeaux, drew attention to the value of autointoxication as a possible organic cause of madness, by organizing and leading a panel on 'Auto-intoxication in Mental Disease'. This topic had been the subject of Chevalier-Lavaure's doctoral dissertation in 1890, the fi rst substantive treatment of this issue in the history of psychiatry (Chevalier-Lavaure, 1890). In their joint presentation they argued that it was diffi cult to distinguish between cases of autointoxication and those of infection from sources outside the body, but that a clear diagnostic distinction should be made between 'infectious' insanity (mental disturbances following acute infectious diseases, such as meningio-encephalitis) and 'visceral insanity', which is 'associated with disease of the internal organs' and is 'also very probably due to autointoxication' [START_REF] Regis | Auto-intoxication in mental disease[END_REF].

Senator (1884) had already proposed that such self-infection would have profound effects on the nervous system and the brain. When Bouchard's book fi rst appeared in English in January 1894, Thomas Oliver (1894: xi) noted in his translator's preface that, 'The part played by auto-intoxication in mental diseases is attracting attention.' In 1895 systematic extensions of autointoxication theory to psychiatry were offered in the German medical literature by D. E. Jacobson of Copenhagen and in the American medical literature by Albert E. Sterne of Indianapolis [START_REF] Jacobson | Ueber Autointoxikationspsychosen[END_REF][START_REF] Sterne | Toxicity an as etiology of nervous disease[END_REF]. Even Julius von Wagner-Jauregg (1857[START_REF] Owensby | Homosexuality and lesbianism treated with metrazol[END_REF], who would later win a Nobel Prize for his therapy for neurosyphilis, speculated that disturbed mental states may be caused by the infl uence of intestinal toxins on brain cells (Wagner-Jauregg, 1896). In psychiatric circles the gastrointestinal tract continued to be the most often cited aetiologic locus of 'autointoxication psychoses' [START_REF] Jahn | Die gastrointestinalen Autointoxikationspsychosen des spaeten 19. Jahrhunderts[END_REF].

Poisoning by internal secretions

The rise of the bacteriological paradigm after 1880 had initiated and fuelled autointoxication theory. Between 1890 and 1905 -the year Ernest Starling fi rst proposed the modern concept of the 'hormone' -advances in the understanding of metabolic processes and the endocrine system added a new endogenous aetiological hypothesis: metabolic or 'interstitial autointoxication' [START_REF] Ewald | Die Autointoxication[END_REF] due to the over-or under-production of internal secretions in the glands with ducts (liver, pancreas and kidney), those without ducts (thyroid, adrenals, pituitary), and especially the sex glands (gonads). Prior to World War I there was considerable confusion in the emerging discipline of endocrinology regarding the nature of hormones and their similarities to enzymes, general metabolites, toxins, antitoxins and vitamins. Some researchers proposed that several of these latter substances, when imbalanced in the body, could be the agents of autointoxication.

With the rising infl uence of focal infection theories after 1900, some theorists sought to combine the classical form of autointoxication theory with the new focus on the possible poisoning effects of an over-or under-production of internal secretions. Perhaps the pathology of the glands (which could affect the brain if the glandular disease was chronic) was secondary to infections arising from the intestines, the mouth or other areas of focal infection. The proposed causal path from focal infection (somewhere in the body) to gland to brain added a level of complexity to an already vague and relatively unsupported theory. This extended model of the mechanisms underlying nervous and mental disorders was rejected by the American psychiatrist Francis X. Dercum (1856Dercum ( -1931)), a forceful proponent of autointoxication theory in psychiatry and a fi ercely sceptical opponent of the psychogenic theories of dementia praecox of the followers of Adolf Meyer (1866Meyer ( -1950) ) and psychoanalysts such as Sigmund Freud (1858Freud ( -1939) ) and Carl Gustav Jung (1875Jung ( -1961) ) that were ascendant in US psychiatry by the time of World War I. According to Dercum (1917: 907), '… on the whole, it may be safely said that when there are present marked or persistent nervous symptoms, we have to deal with a coexistent and probably primary interstitial or endogenous poisoning.' Others, including Kraepelin, were inclined to agree.

Kraepelin's autotoxic aetiology of dementia praecox

In his History of Psychiatry, Edward Shorter (1997) made the case that Kraepelin's clinical psychopathological method led to functional defi nitions of mental disorders which replaced attempts by neurologists to found psychiatry on the clinical-anatomical methods of neuropathology, thus bringing to an end what Shorter termed 'the fi rst biological psychiatry'. This is accurate if 'biological psychiatry' is understood as encompassing only neuropathology and theories of heredity/degeneration. Whereas neuropathology in psychiatry may have run its course by the 1890s (and even this is debatable), it was at this time that degeneration theory was infl aming both physicians and the general public with a hectic fl ush of paranoia concerning heredity. It was also during this decade of the fi n de siècle that the rising medical disciplines of bacteriology, endocrinology and immunology became sources for the generation of new organic hypotheses in biological psychiatry. Kraepelin and his creation, dementia praecox, cannot be comprehended if we remain in the limiting context of [START_REF] Shorter | A History of Psychiatry, from the Era of the Asylum to the Age of Prozac[END_REF] 'fi rst biological psychiatry'. If, instead, Kraepelin and his ideas are examined within the cognitive categories of the 'lost biological psychiatry' of a century ago, a new image emerges.

Impressed with recent advances in the understanding of metabolic disorders and with the plausibility of autointoxication theory, Kraepelin positioned his new diagnostic entity of dementia praecox squarely within the context of these new medical paradigms. In the general discussion of the causes of the insanities that opens the 1896 fi fth edition of his Psychiatrie, Kraepelin (1896: 36-7) notes that many of the characteristic signs of glandular or metabolic disorders appear during the development of mental deterioration, especially in dementia praecox. Later in this book, in his very fi rst detailed description of dementia praecox in a chapter on metabolic disorders (Die Stoffwechselerkrankungen), Kraepelin (1896: 439;1987: 23) states that he has 'serious objections' to the point of view that dementia praecox is caused by 'inadequate constitutional faculties' or 'hereditary degeneration (erblischen Entartung)'. Instead, he offers an alternative hypothesis: 'I consider it more likely that what we have here is a tangible morbid process in the brain (einen greifbaren Krankheitsvorgang im Gehirne). Only in this way does the quick descent into severe dementia become at all comprehensible.' He admits the failure of neuropathological studies to fi nd any characteristic cellular pathology in dementia praecox, but attributes this to an inadequate effort to search for such morbid changes.

What then causes this 'tangible morbid process in the brain' if it is not heredity? Kraepelin (1987: 23) is clear on this point: 'In light of our current experience, I would assume that we are dealing here with an autointoxication (Selbstvergiftung), whose immediate causes lie somewhere in the body.' Kraepelin, however, makes a major departure from classic autointoxication theory by rejecting the intestines as the source of toxins. Instead, Kraepelin posits the locus morbi in the gonads:

If we consider the tendency for the illness to strike at the age when sexual development is still taking place, then it is not out of the question for there to be a connection between the illness and some processes taking place in the sexual organs. These are, of course, only provisional and very indefi nite hypotheses.

Kraepelin's metabolic autointoxication theory of dementia praecox was not uniformly welcomed by psychiatrists. Perhaps the most direct attack on this thesis came from Meyer, soon to become one of the most prominent psychiatrists in the USA. In his review of the 1896 fi fth edition of Kraepelin's textbook, Meyer (1896: 302) was prescient: 'As long as chemistry can not furnish more accurate data and methods, the theory of intoxication and autointoxication so often resorted to by Kraepelin will be a terminus technicus for our ignorance'. At about this time Meyer, a pathologist familiar with the autopsy suites of asylums, was beginning the process of losing faith in psychiatric neuropathology and was wary of converting to the simplistic salvation offered by believers in a new medical creed. By 1903 Meyer would no longer be among the 'brain spot men' at war with the 'mind-twist men', as the Boston neuropathologist E. E. Southard (1876Southard ( -1920) ) termed the two emerging factions in psychiatry [START_REF] Southard | The mind twist and the brain spot hypotheses in psychopathology and neuropathology[END_REF]. Instead, Meyer would essentially switch sides and prepare the path for the insurgency of the Freudians in North America and Great Britain with his 'dynamic psychiatry' and its focus on psychosocial forces such as 'habit-deterioration' and 'reactions'.

But critics of the autointoxication theory of dementia praecox such as Meyer were in the minority. Kraepelin remained convinced. In the 1899 sixth edition of his textbook, he continued to make the argument that the sex glands are the source of the toxins that poison the brain and produce dementia praecox. In this edition, however, his claims were more textured:

In view of the close connection for the disease with the developmental age, with menstrual disorders and reproduction, and in view of the absence of any recognizable external cause, the most obvious thing to think of is probably an autointoxication which could possibly be in some close or distant connection with processes in the genital organs. (Kraepelin, 1990: 154;original italics) To support this speculation, Kraepelin referenced the review article on this subject by [START_REF] Jacobson | Ueber Autointoxikationspsychosen[END_REF]. However, Kraepelin tempered his earlier dismissal of the role of heredity in the cause of dementia praecox, adopting a view that presages modern vulnerability models of the aetiology of schizophrenia [START_REF] Zubin | Vulnerability -a new view of schizophrenia[END_REF]: 'The frequency of hereditary disposition to mental disturbances and their physical and mental symptoms would only signify a lowered resistance to the actual cause of the disease.' Future scholars who examine Kraepelin's views of heredity should refl ect the evolving sophistication of his views.

Kraepelin's dementia praecox was increasingly cited in the German medical literature, with at least twenty such references by the year 1900. However, although some accepted autointoxication as the probable cause of the disease, most diverged from Kraepelin by insisting that the intestines were the true locus of the 'self-infection' and not the sex glands. Metabolic autointoxication as a possible cause of dementia praecox was a hypothesis that intrigued Kraepelin for at least two decades. In the third volume of the fi nal, eighth edition of his Psychiatrie, Kraepelin (1913, III/II: 931) cautiously asserted that it was still too early to draw an aetiological conclusion about dementia praecox, but that it might generally be said that, 'a number of facts (eine Reihe von Tatsachen)' about dementia praecox suggest 'an autointoxication as a result of a metabolic disturbance might be probable to a certain extent (einer Selbstvergiftung infolge einer Stoffwechselstorung bis zu einem gewissen Grade wahrscheinlich). ' Kraepelin's autotoxic aetiology of dementia praecox commandingly framed the cognitive categories of his peers, a fact also forgotten by historians. For example, several prominent German and Swiss psychiatrists who made contributions to the understanding of dementia praecox in the early twentieth century also suspected an 'autotoxin' might be its cause. William Weygandt (1870-1939), an associate of Kraepelin who is best remembered for his monograph on the nature of 'mixed states' in manic-depressive insanity, wrote in 1907 that: Dementia praecox, in particular, is more and more regarded as an illness based on some metabolic disturbance. … I should like to put forward a tentative explanation of dementia praecox of my own. … I would suggest that so far as the organic side is concerned the most plausible concept is one of autotoxic damage affecting genetically predisposed brains. [START_REF] Weygandt | Kritische Bermerkungen zur Psychologie der Dementia praecox[END_REF]1987: 47-8) In this same article Weygandt was critical of the illogic of the chimeric psychoanalytic/autointoxication theory of dementia praecox put forth by Jung in his famous 1907 monograph on the subject, Uber die Psychologie der Dementia Praecox: Ein Versuch. Jung (1936: 89) proposed that a 'complex' created by an intensely emotional event might lead to the production of a biological 'hypothetic X, metabolic toxin (?)'. The persistence of the complexwhich could be removed through psychoanalysis -produced a chronic autointoxication which acted on the brain to produce dementia praecox. However, even Jung admitted in his monograph that the autotoxic process might be primary and unaffected by psychotherapy. Jung's chief, Bleuler, also (for a time) held to this same chimeric theory of the aetiology of dementia praecox. Despite his short-lived infatuation with Freud and his disagreement with Kraepelin on issues such as prognosis, Bleuler made it clear in his classic Dementia Praecox, oder die Gruppe der Schizophrenien, published in 1911, how infl uential Kraepelin's aetiological hypothesis remained in his thinking: 'As long as the real disease process is unknown to us, we cannot exclude the possibility that various types of auto-intoxication or infections may lead to the same symptomatic picture.' (Bleuler, 1950: 279).

Dementia praecox as a disease arising secondarily from metabolic disorders causing autointoxication remained a central (if unsupported) aetiological hypothesis for its fi rst 40 years (see, for example, [START_REF] Lewis | Research in Dementia Praecox[END_REF]. Kraepelin apparently held to this view of the cause of dementia praecox to the end of his life. And although he believed dementia praecox was probably not curable, he believed for a time that it was potentially preventable and might be diluted or delayed by a rational therapy based on the autointoxication theory of it aetiology. The evidence in support of this assertion is that Kraepelin himself tried out numerous experimental therapies derived rationally from autointoxication theory.

Kraepelin's rational treatment for dementia praecox: organotherapy

There were many symptoms that Kraepelin had noticed in dementia praecox patients that paralleled those he had observed in persons with metabolic disorders, especially cases of myxoedema. One of the consequences of chronic hypothyroidism is what is now termed 'myxedematous psychosis' (Heinrich and Grahm, 2003), and it includes progressive dementia, delirium, hallucinations and delusions. Besides these psychological similarities to many cases of dementia praecox, Kraepelin also (incorrectly) believed there were identical physical stigmata: the enlargement of the thyroid gland, bradycardia and tachycardia, skin changes, tremors, changes in pupil size and exopthalmos. By 1896 he had conceptually linked dementia praecox to the 'myxoedematous insanity' caused by thyroid disease. Discussions of dementia praecox immediately follow those of thyroid autointoxication diseases such as myxoedema and cretinism in both the fi fth and sixth editions of Psychiatrie in 1896 and 1899, respectively. Myxoedema was arguably the inspirational source of an analogical transfer Kraepelin made to dementia praecox when trying to discern its essence, a cognitive process that Paul Thagard (1999: 134-47) argues is typical in the explanation of new diseases.

Kraepelin was aware of the fact that the British physiologist Murray had found a cure for myxoedema in 1891. Murray's technique -the hypodermic injection of thyroid extract into myxoedematous patients -became the basis for a new and widely-applied medical treatment, soon called 'organotherapy' [START_REF] Borrell | Organotherapy, British physiology, and the discovery of internal secretions[END_REF]. A major proponent of thyroid organotherapy in the early twentieth century, Philadelphia physician Charles Eucharist de Medici Sajous (1852Sajous ( -1929)), had worked with Brown-Sequard in Paris from 1892 to 1897 and was singularly responsible for popularizing this treatment in North America [START_REF] Tattersall | Hypoadrenia or "a bit of Addison's Disease[END_REF][START_REF] Wilson | Sajous and the hundredth anniversary of The Internal Secretions and the Principles of Medicine[END_REF]. Like many proponents of thyroid organotherapy, Sajous praised its effects in terms worthy of only the most miraculous panacea. Not only did it cure conditions caused by hypothyroidism, but it had systemic rejuvenating effects of the entire body by eliminating sources of autointoxication:

It renders the phosphorous of all tissues, and all free substances, such as bacteria, wastes, toxins, etc., containing phosphorous, more infl ammable or insensitive to the action of oxygen in the blood. … this applies particularly to nerves and nerve-centers (all of which are especially rich in phosphorous) … This is not all, however … the functions of all organs are enhanced by this process … [which] are the active destroyers of pathogenic organisms, toxins and other poisons … It counteracts premature senility in all its phases … (Sajous, 1921: 708-9;original italics) Organotherapy, particularly thyroid organotherapy, was applied as a treatment for insanity by numerous physicians of several nationalities by the late 1890s with mixed results (for a review of this literature, see Sajous, 1921: 711-16). At some point, probably in the mid-1890s, Kraepelin had also tried such experiments on his patients. In 1913 Kraepelin wrote:

Many years ago I endeavored for a long time to acquire infl uence on dementia praecox by the introduction of preparations of every possible organ, of the thyroid, of the testes, of the ovaries and so on, unfortunately without any effect. (Kraepelin, 1919: 278) Organotherapy, a treatment rationally derived from his presumed aetiology of autointoxication, was eventually abandoned by Kraepelin. He offered no suggestions for other rational treatments for autointoxication. Instead of suggestions for prevention or treatment of the causes of dementia praecox (which were unknown), Kraepelin emphasized custodial care in his writings. In the pre-antibiotics era there was one additional rational therapy for autointoxication that Kraepelin was not willing to explore: surgery. But there were others, particularly in the USA, who were not so cautious.

The reception of dementia praecox in America

Following the publication of the sixth edition of Kraepelin's Psychiatrie in 1899, dementia praecox gradually became an accepted diagnostic entity in Britain (Ion andBeer, 2002a, 2002b) and America, where the fi rst medical publications on dementia praecox began to appear in 1900 [START_REF] Brownrigg | A general view of dementia praecox: translated from the German of Kraepelin[END_REF][START_REF] Gershom | Dementia praecox[END_REF][START_REF] Noble | Dementia praecox[END_REF][START_REF] Noll | The American reaction to dementia praecox[END_REF]. In these fi rst American notices of 1900, the importance of Kraepelin's new scientifi c nomenclature is uniformly lauded, with heredity mentioned as the most probable cause of the disorder. Autointoxication is not mentioned. This would change as the literature on dementia praecox increased, with autointoxication growing in prominence as an organic aetiology, reaching its height in American medicine during World War I. According to Bayard Taylor Holmes (1852Holmes ( -1924) ) -a Professor of Surgical Pathology and Bacteriology at the College of Physicians and Surgeons in Chicago who published the most extensive bibliography documenting the autointoxication hypothesis of dementia praecox [START_REF] Holmes | A guide to the documents in evidence of the toxaemia of dementia praecox[END_REF] -the medical literature on dementia praecox evolved in the following way:

Beginning about 1904 the literature on dementia praecox is of two sorts, one stream following the ideas of Freud, Jung and Bleuler, who attribute origin of the disease to psychogenetic factors, and the other maintaining the steady course of mechanistic pathology. The French and the English schools have generally held to the physical basis of the disease, while the German and American faculties have been divided into two irreconcilable factions. In the early part of the present decade the mystics and the psychogenists held the fi eld and the programs of the annual meeting of Alienists and Neurologists in America are signifi cant of the fact that Freudianism is on the decline and rational materialistic or mechanistic studies of the disease are in a growing ascendancy. (Holmes, 1916: 391) The reception of dementia praecox in American popular culture began about the year 1907. It was in this year that the term made its fi rst appearance in The New York Times (as a point of comparison, the word 'schizophrenia' did not appear in this newspaper until 1925). 'Dementia praecox' fi rst came to the attention of the American public in nationwide newspaper articles in March 1907 reporting the testimony of alienists on the mental health of New York millionaire Harry Thaw (1871-1947) during his trial for murder. 1 On the night of 25 June 1906, Thaw fi red three shots into the face and shoulder of the famous American architect Stanford White , killing him instantly. The murder occurred during a rooftop theatre garden event at Madison Square Garden, a building that White had designed and in which he maintained a 'tower apartment' where he would entertain friends and young women, some of whom were encouraged (after champagne or absinthe) to remove their clothes and soar, to-and-fro, almost to the ceiling, on a red velvet swing. Thaw's wife, Evelyn Nesbit (1885-1967), a beautiful model and actress, had previously been White's mistress. She had once been one of the girls on the red velvet swing. But sexual jealousy was not the exclusive factor in this very public and violent act. A smouldering madness had infl amed Thaw's brain since puberty. Thaw was judged insane the following year during what was then called the 'trial of the century'. He was sent to an asylum for the criminally insane. The trial inspired numerous books, both fi ction and nonfi ction, and the story appeared in fi lm in the 1981 motion picture Ragtime (based on the novel by E. L. Doctorow).

US newspapers provided daily coverage of the testimony of the numerous prominent American alienists concerning the proper medical diagnosis of Thaw's 'brainstorm' (as some alienists termed it). Dr Charles G. Wagner, the Superintendent of the Binghamton Asylum in New York, testifi ed that one of Thaw's possible diagnoses was 'dementia praecox' -a term ridiculed during the closing statements in the trial. This dreadful-sounding insanity had never before been uttered in a US courtroom, nor had it ever appeared in the pages of the USA's major newspapers, and the introduction of this previously unknown illness during the Thaw trial induced as much mystery as fear in the fascinated public.

After the press coverage of the Thaw trial, the term 'dementia praecox' was lodged fi rmly into the collective consciousness of Americans. Practising physicians as well as average citizens knew the term -and the sound of it! The heavy, dark effect on the emotions of listeners when they heard it spoken matched its commonly understood meaning: chronic incurable insanity. American alienists and neurologists living in an era increasingly marked by an attitude of pragmatism and progressivism were not happy with Kraepelin's term, its literal meaning or its fatalistic prognosis. 'Perhaps no more unfortunate term than dementia praecox has yet been devised for an important group of psychopathic patients,' complained Southard and Jarrett (1922: 298-9). Some suggested that American psychiatrists should invent their own diagnostic term and criteria. A few did just that, but none of the American alternatives stuck: the Thaw trial of 1907 made dementia praecox a household word. It was not until 1918 or so that an alternative term -schizophrenia -began to gain currency among some American physicians. 2 But it too was a foreign import, from Switzerland, and although the prognosis was better, and its wider circle of 'latent schizophrenics' made its treatment theoretically possible through mental hygiene efforts, it also had an ominous ring to it and meant the same thing: chronic incurable insanity.

One additional factor may have led to the adoption of Bleuler's term: Kraepelin was an ardent German nationalist, and this was well known to many psychiatrists in the USA. With anti-German sentiment still running high after the end of World War I, personal resentment of Kraepelin's political views may have led to the gradual rejection of dementia praecox in favour of the term used by the politically benign Bleuler: schizophrenia. 3 Dementia praecox, or the hybrid terms 'dementia praecox (schizophrenia)' or 'schizophrenia (dementia praecox)', remained in offi cial use in the USA until 1952. In addition to its wide recognition among the American public following the 1907 Thaw trial, the term lived on due to its reifi cation in the publications of the National Committee on Mental Hygiene (founded in 1909) and the Eugenics Records Offi ce (1910). Although the diagnosis had fi rst been applied in the USA by Adolf Meyer at the Worcester Lunatic Hospital in Massachusetts in the autumn of 1896, both dementia praecox (in its three classic forms) and 'manic-depressive psychosis' gained wider popularity in the larger institutions in the eastern states after being included in the offi cial nomenclature of diseases and conditions for record-keeping at Bellevue Hospital in New York City in 1903(Board of Trustees …, 1903: 32). But perhaps the most important reason for the longevity of Kraepelin's term was its inclusion in 1918 as an offi cial diagnostic category in the uniform system adopted for comparative statistical record-keeping in all US mental institutions, The Statistical Manual for the Use of Institutions for the Insane (American Medico-Psychological Association …, 1918). Its many revisions served as the offi cial diagnostic classifi cation scheme in the USA until 1952 when the fi edition of the Diagnostic and Statistical Manual of Mental Disorders, or DSM-I, appeared [START_REF] Apa | Diagnostic and Statistical Manual of Mental Disorders (DSM-I)[END_REF]. Dementia praecox disappeared from offi cial psychiatry with the publication of DSM-I, replaced by the Bleuler/Meyer hybridization 'schizophrenic reaction' within the category of 'psychogenic' disorders.

Although Kraepelin's term survived more than half a century in America, his aetiological hypothesis did not. Meyerian and Freudian insurgencies among alienists and neurologists in America tilted the balance towards environmental and psychogenic causes, although most of the 'mind-twist men' would admit that organic factors clearly played a role in the pathophysiology, if not the aetiology, of dementia praecox. However, among the remaining 'pure' biological psychiatrists and neurologists in the USA, the preferred biological theory of the aetiology of dementia praecox was Kraepelin's: autointoxication. According to neurologist Francis X. Dercum (1917: 908) of Philadelphia, 'a striking instance of a chronic intoxication of the nervous system and one that in addition is purely an autointoxication is that furnished by dementia praecox'. Following Kraepelin, Dercum believed dementia praecox was caused by 'a toxic hormone which gains entrance into the circulation from the sex glands'. However, Dercum's focus on the sex glands was rare among Americans. There were confl icting views as to which of the two varieties of autointoxication -intestinal or interstitialwas implicated, or whether there was some combination of the two (focal infection in the intestinal tract affecting the production of internal secretions, then lastly the brain).

Prevention, treatment and cure were the hopes held out by adhering to an autotoxic aetiology for dementia praecox. These were consistent with the progressivism and pragmatism at the core of American values so exemplifi ed by the National Committee on Mental Hygiene and the Eugenics Records Offi ce. Organotherapy and surgery became the two rational organic treatments applied to the fi ght against dementia praecox in America. Organotherapy yielded meagre results and was quickly discarded. Instead, surgery became the treatment of choice among biological psychiatrists. The thyroid, the intestinal tract and the mouth would become the three most commonly targeted areas of the body for the prevention, treatment and cure of dementia praecox.

Thyroid surgery

The fi rst major American newspaper article to discuss dementia praecox in a medical context was published in The New York Times on 20 December 1907. The context was metabolic autointoxication, and the article summarized a surgical cure for this insanity. This news report is indicative of the pattern that the reception of Kraepelin's autointoxication theory of dementia praecox took in America: the rush to attempt radical treatments without waiting for conclusive scientifi c evidence of actual sources of self-poisoning in the body.

The surgery was performed by Newdigate Owensby (1882Owensby ( -1952)), an alienist at the Bay View Asylum in Highlandtown (near Baltimore), Maryland. In his later career Owensby would become one of the fi rst psychiatrists to practise in the southern state of Georgia, and he still maintains a certain notoriety for a 1940 study in which he used aggressive 'metrazol storm' treatments and electroshock therapy to cure homosexuality [START_REF] Owensby | Homosexuality and lesbianism treated with metrazol[END_REF]. The brief newspaper report (Anon., 1907) is reproduced in full below. Note Owensby's congruence with Kraepelin's aetiological speculation about dementia praecox as the result of metabolic autointoxication (though positing the locus morbi in a different gland).

Cures dementia praecox

Surgeon discovers operation to relieve disease of mind BALTIMORE, Md. Dec 19.-A cure for one of the most pitiable forms of insanity, hitherto considered by experts as 80 per cent incurable, has been found, it is hoped, in the use of the surgeon's knife by Dr. Newdigate M. Owensby, physician in chief at Bayview Insane Asylum. This form of insanity is known to the profession as dementia praecox.

It attacks persons generally between the ages of 15 and 30 years. It destroys the qualities of resistance, thought, and speech, rendering the victim little more than an idiot.

The disease resembles in certain symptoms the more familiar forms of cretinism and myxoedma, and it was this similarity that fi rst led Dr. Owensby to conceive of an operation. The two latter diseases originate, it is thought, by a lack of secretion in the thyroid gland, located near the windpipe. A fairly effective cure was found in the administration of extract of thyroid glands taken from sheep.

Following this line of treatment in dementia praecox, Dr. Owensby found that instead of reducing the symptoms the treatment seemed to accentuate them. He concluded that instead of the disease arising from a lack of secretion, there was a likelihood of oversecretion, due to diseased blood vessels in the gland. This suggested using the knife to cut away the diseased portion, giving opportunity for new blood vessels to form. Dr. Owensby last July performed the operation on the worst case in the asylum. The case was kept under close observation for two months, without the slightest indication of a return of the symptoms. In October the case was dismissed. The man has secured employment and is doing intelligent work.

Of four other cases operated upon, three showed the same return of intelligence.

Hyperthyroidism as the cause of dementia praecox was also assumed by endocrinologist Sajous (1921: 715) of Philadelphia: 'In dementia praecox we have the opposite condition, i.e., hyperthryoidia as the underlying cause.' Surgery to remove part of the thyroid was his recommended treatment. Kraepelin (1919: 278), 'with expectancy', followed the literature on the 'partial excision of the thyroid gland', but noted that most of the attempts to cure dementia praecox with surgery had ended in failure or mixed results. There is no evidence to date that Kraepelin experimented with this radical -but rational -form of treatment.

Intestinal and other forms of surgery

Other surgical solutions for dementia praecox were also based on autointoxication theory, but not the metabolic variant supported by Kraepelin. Instead, attempts to cure dementia praecox by the surgical removal of sites of focal infection in the intestines and elsewhere were attempted by Holmes of Chicago (Noll, 2006a(Noll, , 2006b(Noll, , 2006c) ) and Henry A Cotton (1876-1933) of the Trenton State Hospital in New Jersey [START_REF] Scull | Madhouse: A Tragic Tale of Megalomania and Modern Medicine[END_REF]. Sajous (1921: 716) believed that, 'The cause [of dementia praecox], whether tonsillar, dental, intestinal, etc., of the thyroid erethism [causing hyperthyroidism], must be removed. Bayard Holmes and also myself have cured severe cases by fl ushing the colon through an abdominal opening.' The metabolic autointoxication theory of dementia praecox continued to inspire a minority of researchers, including the noted N. D. C. Lewis (1889Lewis ( -1979)), spawning a variety of endocrinological research studies and experimental organotherapy treatments, all of which led to blind alleys [START_REF] Lewis | Constitutional Factors in Dementia Praecox, with Particular Attention to Circulatory System and Some of the Endocrine Glands[END_REF]1936). When autointoxication fi nally became a 'deceased disease' by 1936 [START_REF] Riesman | Deceased diseases[END_REF], so did the linkage of dementia praecox to either of its metabolic or intestinal variants. Heredity, however, remained throughout the twentieth century as an aetiological alternative supported by genetics studies, and it continues to be so today. With the ascendancy of Meyerian psychobiological and Freudian psychoanalytic perspectives that increasingly turned attention away from the biological basis of dementia praecox (schizophrenia), Kraepelin's autointoxication theory slid further into oblivion. Perhaps this is why Kraepelin's views on the probable cause of dementia praecox have been so incomplete in the literature on the history of psychiatry.

Notes

1. The Thaw trial and the negotiations among American alienists and neurologists regarding the reception of Kraepelin's dementia praecox concept will be detailed in my forthcoming book, The New Peril: Dementia Praecox in America, , which is scheduled to be published by Harvard University Press in 2008. 2. According to Lunbeck (1994: 373), schizophrenia was fi rst used as a diagnostic term at the Boston Psychopathic Hospital in 1919. E. E. Southard, who was the medical director of that hospital, wrote to several colleagues about this time to ask their opinion on the comparative desirability of the two terms. He summarized them in notes attached to his unpublished typescript, 'Non-Dementia Non-Praecox: Note on the Advantages to Mental Hygiene of Extirpating a Term' (held among his Nachlass at the Countway Library of Medicine at Harvard Medical School). The unpublished paper was the basis of a lecture he delivered to the Boston Society of Psychiatry and Neurology on 20 February 1919. To cite two examples: the Swiss-American psychiatrist August Hoch (1868-1919) agreed with Southard that the term dementia praecox was problematic. However, he added: 'I am not especially pleased with schizophrenia. It is a rather uncouth term, and I remember, when it fi rst came out, how I balked at it and how, when I read my review of Bleuler's schizophrenia at the New York Psychiatrical Society, all of them made a lot of fun of the term. But it is remarkable what one can get used to.' Another Swiss-American psychiatrist, the eminent Adolf Meyer, also detested the term, telling Southard, 'I hope that the elimination of the term schizophrenia will follow.' However, he began using it formally in public as early as 1921, paving the way for its offi cial acceptance in the USA. (Meyer, 1921(Meyer, -1922))

  '. See E. E. Southard papers, Box 8 [GA 81], Countway Library of Medicine, Harvard Medical School. 3. Kraepelin's fi xation on political issues was apparent to many Americans who came in contact with him after the war. His persistent German nationalism repelled many of the US psychiatrists whom he approached for help in convincing US philanthropists, such as the Rockefellers, for fi nancial backing to support his psychiatric research institute in Munich. Reports of such unappealing encounters with Kraepelin can be found in the correspondence of Adolf Meyer with several colleagues (especially David K. Henderson and George H. Kirby), held in the Adolf Meyer Collection, the Alan M. Chesney Medical Archives, Johns Hopkins University, Baltimore Maryland.


Talya Greene
email: talya10@hotmail.com

The Kraepelinian dichotomy: the twin pillars crumbling?

Keywords: affective disorder, classification, Emil Kraepelin, Kraepelinian psychiatry, psychosis, schizophrenia, 20th century

Emil Kraepelin's view that psychotic disorders are naturally-occurring disease entities, and that dementia praecox and manic-depressive psychosis represent two different diseases, has been hugely influential on classificatory systems for psychosis. Corresponding to the Kraepelinian dichotomy, those systems generally differentiated schizophrenia from affective psychosis. This paper examines the debate that took place between 1980 and 2000 regarding this differentiation. During the 1980s, the scientific reliability of the diagnostic criteria was challenged. In the 1990s there were significant critiques of the validity of the Kraepelinian dichotomy. Yet the dichotomy has not been formally abandoned, and the discussion continues to the present day. This paper suggests that before psychiatry can abandon the Kraepelinian dichotomy, a new model for conceptualizing and describing psychotic symptoms may be required.

Introduction

Emil Kraepelin's view that psychotic disorders could be conceptualized as naturally-occurring disease entities which could largely be differentiated into dementia praecox and manic-depressive psychosis, has had a huge impact on twentieth-century psychiatry. The rise of neo-Kraepelinian psychiatry in the 1960s and 1970s contributed to the construction of DSM-III, in which the Kraepelinian dichotomy between schizophrenia and psychotic affective disorders became embedded in psychiatric classifi cation. Nevertheless, there have been repeated challenges to the Kraepelinian conceptual framework throughout the twentieth century. This paper examines the debate that took place from the publication of DSM-III in 1980 to the end of the twentieth century regarding the Kraepelinian division of schizophrenia and psychotic affective disorders.

Background

At the turn of the twentieth century, Kraepelin proposed that psychotic mental disorders could be understood as expressions of real biological illnesses. In 1883 he published his 385-page textbook of psychiatry [START_REF] Kraepelin | Compendium der Psychiatrie zum Gebrauche für Studierende und Aerzte[END_REF]. Drawing on the traditions of nineteenth-century science, Kraepelin developed a nosological system of classifi cation for serious mental illnesses which were published in nine successive editions of his textbook. By the fi nal edition [START_REF] Kraepelin | Psychiatrie[END_REF], it had grown to a two-volume publication with 2425 pages. Throughout these years, Kraepelin maintained that mental illness consisted of a fi nite number of natural disease units, each with its own distinct pattern of symptoms, aetiology and anatomy. Kraepelin argued that 'aspects' or symptoms carried information as to the 'essence' of disease, and that symptomatology, therefore, could provide a means for classifying disease.

In the sixth edition of Psychiatrie published in 1899, Kraepelin presented catatonia and dementia paranoides together with hebephrenia as forms of dementia praecox [START_REF] Kraepelin | Clinical Psychiatry: A Text-Book for Students and Physicians, translated and[END_REF]. (The Swiss psychiatrist, Eugen Bleuler, would later rename dementia praecox as schizophrenia; Bleuler, 1911[START_REF] Bleuler | Dementia Praecox or the Group of Schizophrenias Translated by J. Zenkin[END_REF] In this edition, Kraepelin clearly proposed the separation of dementia praecox from manic-depressive psychosis (now referred to as bipolar disorder). He asserted the dementia praecox was caused by 'a defi nite disease process in the brain' (Kraepelin, 1902: 153). He claimed that 'in a few cases this is a reparable lesion, but in most cases the impairment of function is permanent and progressive ' (p. 283). In manic-depressive illness, however, the main aetiological factor was considered to be defective heredity. Manic-depressive illness was also seen to have a better prognosis than dementia praecox.

Towards the end of his career, Kraepelin began to have some doubts about his system. In 1920 he published an article on 'The Manifestations of Insanity' in which he argued that psychiatric illness could be understood as groups of symptoms generated by underlying patterns of brain activity [START_REF] Kraepelin | The manifestations of insanity' by Emil Kraepelin[END_REF][START_REF] Kraepelin | The manifestations of insanity' by Emil Kraepelin[END_REF]). He claimed that 'we naturally will then turn our attention from merely classifying and categorizing diseases to a more exalted and satisfying exercise -understanding disease processes and how they inter-relate ' (p. 509). He abandoned the view that psychotic symptoms were specifi c to a particular pathology. He argued:

The learnt mental mechanisms which give rise to these manifestations of disease are not confi ned to a particular disease process, but can be evoked in the same form by a variety of morbid insults … we must be very wary of claiming that a particular disorder is characteristic of one and only one particular disease process. (p. 518) Although he had previously argued for the differentiation of manic-depressive insanity from dementia praecox, Kraepelin ultimately concluded: 'we cannot satisfactorily distinguish between these two diseases. The suspicion remains that we are asking the wrong questions' (p. 527). Despite Kraepelin's concerns in 1920 about his theories, in the eighth edition of Psychiatrie he maintained that 'the proof is furnished that our picture is in the main agreeable to natural law' [START_REF] Kraepelin | Dementia Praecox and Paraphrenia[END_REF](Kraepelin, /1971: 252): 252). Even in the 1920 article in which he discussed the diffi culties in adequately distinguishing between dementia praecox and manic-depressive illness, he still argued that 'the two disease processes themselves are distinct' [START_REF] Kraepelin | The manifestations of insanity' by Emil Kraepelin[END_REF][START_REF] Kraepelin | The manifestations of insanity' by Emil Kraepelin[END_REF]: 527). He concluded that 'this distinction is too overwhelming for us to accept much overlap between the two groups, particularly as we can often predict the course of the two from the clinical signs' (p. 528). Ultimately, he said, 'we must at all costs adhere to the basic difference between the disease processes concerned' (p. 528).

Thomas [START_REF] Kuhn | The Structure of Scientifi c Revolutions[END_REF] argued that science works within paradigms, or schools of thought, that shape research questions, methodologies and concepts. Kraepelin's nosological system was hugely infl uential throughout the last two decades of the twentieth century, particularly with regard to the separation between schizophrenia and affective psychoses, so much so that the Kraepelinian model became the central paradigm for psychiatry [START_REF] Ion | The British reaction to dementia praecox. 1893-1913. Part 1[END_REF][START_REF] Jablensky | Kraepelin's legacy: paradigm or pitfall for modern psychiatry[END_REF][START_REF] Van Bakel | Emil Kraeplin and Wundtian experimental psychology[END_REF]. As J. P. [START_REF] Gueguen | History of the concept of schizophrenia[END_REF]Gueguen ( /1997: 2) : 2) writes, Kraepelin, 'through a rigorous clinical approach, found[ed] all the great nosological frames, which even today provide a reference for us'. Similarly, Tim Crow (1990: 790) points out that the Kraepelinian dichotomy: has fared so well that no respectable textbook is without separate chapters on the two 'diseases' and much of the impetus behind modern operation diagnostic criteria (DSM-III and so forth) is directed at distinguishing these supposed entities with maximum reliability.

Despite the apparent dominance of the Kraepelinian system, there are many historians and mental health clinicians who now challenge it, questioning whether the paradigm is a 'true' system that corresponds to real disease entities. Berrios, Luque and Villagrán (2003) argue that a 'continuity myth' has been constructed. According to the myth, schizophrenia has always existed, was discovered by Kraepelin, and since then psychiatrists have been improving and refi ning concepts and knowledge of it. This approach implies that it is only a matter of time before the genetics and aetiology of schizophrenia are understood. Berrios et al. (2003: 115) go so far as to state that this 'myth … is almost beyond the reach of empirical correction or falsifi cation'.

In 1952 the Diagnostic and Statistical Manual of Mental Disorders (later, DSM-I) was published by the American Psychiatric Association [START_REF] Apa | Diagnostic and Statistical Manual of Mental Disorders[END_REF]. A number of different psychiatric diagnostic manuals had previously been published, mainly for use in mental hospitals, and DSM-I represented an attempt to standardize diagnoses [START_REF] Compton | The neo-Kraepelinian revolution in psychiatric diagnosis[END_REF]. In DSM-I, most disorders were referred to as 'reactions' precipitated by environmental events. All people were considered to react to their environment to a certain extent, and mental disorders were therefore seen as a question of degree rather than of kind. In 1968 DSM-II was published [START_REF] Apa | Diagnostic and Statistical Manual of Mental Disorders[END_REF]. The stated aim of this second edition was to facilitate 'maximum communication within the profession and reduce confusion and ambiguity to a minimum' (APA, 1968: viii). This version was heavily infl uenced by psychoanalysis, which was then at its peak in the USA. Most conditions were referred to as neuroses rather than as reactions. The descriptions were brief and did not contain much indication of the clinical criteria required for diagnosis.

By this time, the anti-psychiatry movement of the 1960s and early 1970s had begun to challenge the Kraepelinian basis for concepts of psychosis. Ronald D. Laing, a Scottish psychiatrist, made a radical break from the accepted norm by claiming that schizophrenia was not a disease in the classic sense as it had no anatomical or biochemical lesion. Rather, schizophrenia was a reaction to a hopeless situation, in which the individual 'chooses' the symptoms as an exit from intolerable pain [START_REF] Laing | The Divided Self: A Study of Sanity and Madness[END_REF]. Laing (1960: 7) argued that psychiatric disorders were not 'medical illness but a diagnostic designation, arbitrarily fi xed by society and confi rmed by psychiatrists'. Similarly, the US psychiatrist, Thomas Szasz, developed a notion of the uselessness of psychiatry as a discipline. '"Mental illness" is a metaphor', Szasz wrote, 'strictly speaking, disease or illness can affect only the body; hence, there can be no mental illness.' Moreover, he claimed that 'psychiatric diagnoses are stigmatizing labels, phrased to resemble medical diagnoses and applied to persons whose behaviour annoys or offends others' (Szasz, 1974: 267).

In 1973 a US sociologist, David Rosenhan, conducted a study in which he enlisted seven 'normal' associates and instructed them to present themselves to doctors complaining that they were hearing a voice saying 'thud', 'empty' or 'hollow' [START_REF] Rosenhan | On being sane in insane places[END_REF]. Beyond the alleged symptoms and the falsifi cation of names and occupations, the confederates were to act completely normally, and present their life histories as they had actually occurred. The confederates were all given a diagnosis of schizophrenia and committed to psychiatric hospitals. Despite displaying normal behaviour, the pseudo-patients remained hospitalized for 9-52 days, with an average stay of 19 days. At no time during their hospitalization was the legitimacy of their schizophrenia diagnosis called into question. Rosenhan concluded that mental health professionals were unable to distinguish effectively between the sane and insane. This infl uential study challenged both the reliability of the diagnostic criteria for schizophrenia, and the power attached to psychiatric labels.

In response to such attacks on psychiatric classifi cation, a movement developed that reaffirmed the Kraepelinian approach to diagnosis and classifi cation [START_REF] Blashfi Eld | The Classifi cation of Psychopathology: Neo-Kraepelinian and Quantitative Approaches[END_REF]. Gerald L. Klerman (1978: 104) conceptualized this school of thought as 'neo-Kraepelinian'. The neo-Kraepelinian approach took psychiatry to be a branch of medicine that should use modern scientifi c methodologies. Neo-Kraepelinians viewed people with mental illnesses as sick and clearly distinct from healthy people. They asserted that mental illnesses were real pathobiological entities, and that scientifi c psychiatry should investigate the causes, diagnosis and treatment of these mental illnesses, with a particular emphasis on the codifi cation of diagnostic criteria [START_REF] Klerman | The evolution of a scientifi c nosology[END_REF].

The neo-Kraeplinians, although not connected in any official way, worked together to promote their approach. Blashfi eld (1982) described this informal network with their common beliefs, methodologies and research interests as an 'invisible college': there was a tendency among this group to produce papers which actively reinforced one another's fi ndings. Blashfi eld gives as an example a key neo-Kraepelinian paper: 'Diagnostic criteria for use in psychiatric research' published in Archives of General Psychiatry by [START_REF] Feighner | Diagnostic criteria for use in psychiatric research[END_REF], which codifi ed neo-Kraepelinian psychiatric diagnostic criteria. Blashfi eld found that this was cited more than 79 times as often as the average paper published in this journal; he concluded that this was due to the invisible 'college effect' of the neo-Kraepelinian group promoting the Feighner et al. paper by writing many articles that cited it.

The impact of this group could be seen in the third edition of the DSM, published in 1980. Robert Spitzer, a prominent neo-Kraepelinian and the chair of the DSM-III Task Force, was concerned that the challenges over the reliability of psychiatric diagnoses could invalidate the whole of psychiatry [START_REF] Spitzer | A reanalysis of the reliability of psychiatric diagnosis[END_REF]. Spitzer attempted to address this concern in DSM-III by creating precise diagnostic criteria. DSM-III maintained the distinction between schizophrenia and affective psychotic disorders; an absence of affective symptomatology was listed amongst the criteria for a schizophrenia diagnosis. The infl uence of the neo-Kraepelinian movement could be seen in its use of more exacting and operationalized criteria with descriptions of symptoms, aetiology, familial pattern and differential diagnosis, and in the perception of a clear divide between normal and abnormal.

Many psychiatrists saw DSM-III as demonstrating a fundamental or revolutionary change in the approach of psychiatry, moving from psychodynamic theories to an emphasis on science and biology [START_REF] Andreasen | The Broken Brain: The Biological Revolution in Psychiatry[END_REF][START_REF] Maxmen | The New Psychiatrists[END_REF]. Maxmen (1985: 35) stated that 'the ascendance of scientifi c psychiatry became offi cial' by the adoption of DSM-III', and he asserted: 'The old psychiatry derives from theory, the new psychiatry from fact' (p. 31). However, in many ways, DSM-III was a reassertion of Kraepelin's concepts, rather than a revolutionary new approach [START_REF] Ghaemi | The Concepts of Psychiatry: A Pluralistic Approach to the Mind and Mental Illness[END_REF].

The approach characterized by DSM-III could be seen in the work of many psychiatrists in the early 1980s. For example, Irving I. Gottesman and James Shields (1982) published an infl uential book, Schizophrenia: The Epigenetic Puzzle, which was constructed around the assumption that schizophrenia is a real disease, with a genetic basis, and that further research would reveal its nature in full. The authors optimistically and incorrectly declared that 'the schizophrenia puzzle is in the process of being solved before the twentieth century ends' (Gottesman and Shields, 1982: 235). They used a combination of family, twin and adoption studies to lay the foundations for their claims that schizophrenia has a genetic component and is a discrete disease entity. They considered schizophrenia to be comparable to diseases such as diabetes and heart disease, in which only predisposed individuals develop the illness, with environmental factors increasing the risk. A number of other researchers conducted family and twin studies and similarly concluded that there was a genetic basis to schizophrenia and affective disorders, and that the two disorders were independent of each other [START_REF] Gershon | Are mania and schizophrenia genetically distinct?[END_REF][START_REF] Loranger | Genetic independence of manic-depression and schizophrenia[END_REF][START_REF] Reich | Genetics of the affective psychoses[END_REF].

Challenges to the Kraepelinian dichotomy

Despite the claims that DSM-III had brought a revolution in psychiatry, the concepts proposed in it immediately came under scrutiny. While the antipsychiatrists of the 1960s rejected psychiatric concepts and labels on social and political grounds, this next wave of critics looked to empirical evidence to make their case. They placed themselves fi rmly within the scientifi c community, arguing that the concepts formulated about schizophrenia and manic depression were arbitrary classifi catory categories, without scientifi c reliability or validity. Debate during the 1980s centred around the diagnostic criteria for schizophrenia. Particular points of contention were whether schizophrenia could be reliably separated from other psychiatric disorders and whether schizophrenia represented one heterogeneous disease, or whether it was made up of a number of more homogenous diseases.

Robert E. Kendell and Ian Brockington (1980: 326) claimed that Kraepelin's concepts of dementia praecox and manic-depressive insanity became 'the twin pillars on which our classifi cations have been based'. However, they criticized this conceptualization, arguing that if diagnostic categories were to be considered genuine disease entities, 'it should imply a natural boundary or discontinuity' between disorders, and it should be possible to identify this break or, as they termed it, a 'point of rarity' (p. 324; original italics). However, they failed to demonstrate a discontinuity between schizophrenia and the affective psychoses. This led them to conclude that a point of rarity may not exist.

In response, [START_REF] Cloninger | Diagnosis and prognosis in schizophrenia[END_REF] conducted a study in which they mounted a defence of the Kraepelinian dichotomy and attempted to show a discontinuity between psychotic disorders. They used narrower criteria to defi ne the disorders and claimed to have demonstrated a bimodal distribution of psychosis. They concluded that 'there is a natural boundary, or point of rarity, in the symptoms that distinguish schizophrenics from other persons, including both normal subjects and patients with other psychotic and nonpsychotic disorders' (Cloninger et al., 1985: 22). However, this paper stood alone as the only study in which a point of rarity was demonstrated.

According to the Kraepelinian model, if the two disorders were disease entities, with a genetic basis, one would expect to see an increased propensity for schizophrenia in the family members of schizophrenia patients, and an increased propensity for bipolar disorder among family members of those diagnosed with bipolar disorder. Theoretically, if the two disorders were unrelated, there would be no increased likelihood of fi nding bipolar disorder in the family members of schizophrenic patients and vice versa. Furthermore, it would be expected that monozygotic twin pairs would receive the same diagnosis as each other. However, a number of family studies did not seem consistent with the Kraepelinian model, and instead seemed to support Kendell's position that there was no clear boundary between the two disorders. One study described identical male triplets, two of whom were diagnosed with schizophrenia and one with bipolar disorder [START_REF] Mcguffi N | Identical triplets: non-identical psychosis[END_REF]. Another described identical twins, one who had been diagnosed with schizophrenia and the other with bipolar disorder [START_REF] Dalby | Schizophrenia and mania in identical twin brothers[END_REF]. A key family study showed that relatives of schizophrenia patients had an increased likelihood of being diagnosed with bipolar disorder [START_REF] Kendler | Psychiatric illness in fi rst-degree relatives of schizophrenic and surgical control patients: a family study using DSM-III criteria[END_REF]. These studies undermined the case that affective disorders and schizophrenia were discrete disease entities with distinct genetic causes (Stassen, Scharfetter, Winokur and Angst, 1988: 115).

Another important study was published in 1987 by Farmer, McGuffi n and Gottesman. They looked at identical twin pairs and found that out of 27 pairs with one member diagnosed with schizophrenia, six had a pair concordant for schizophrenia, but seven had a pair diagnosed with a mood disorder. Farmer et al. (1987: 634) noted that 'it may be questioned whether it is the genetic control of schizophrenia or the validity of the operational defi nition that is being tested'. They continued, 'it is apparent that DSM-III has not necessarily achieved an optimal placement of the boundaries of schizophrenia, since uncomfortable anomalies have arisen concerning the diagnostic discordance of certain twin pairs' (p. 640). This is a particularly interesting study because while these 'uncomfortable anomalies' could be interpreted as suggesting a connection between schizophrenia and affective disorder, these researchers preferred to argue that the results were due to problems with the DSM-III criteria. This shows the extent to which the Kraepelinian dichotomy was framing the interpretation of results.

Other researchers, however, were calling into question the sharp distinction between the two disorders. Crow recognized that there was a correlation between the type of psychosis seen in a patient and in their family members, declaring that 'without this, the Kraepelinian dichotomy could hardly have survived' (Crow, 1986: 424). However, he also argued that the existence of cases of psychosis with mixed manic affective and schizophrenic symptoms was problematic for the dichotomy. Therefore, he concluded that the 'affective psychoses and schizophrenia are related to each other on a continuum and that this continuum has a genetic basis ' (p. 426). Others came to similar conclusions, continuing to see distinctions between mixed manic affective and schizophrenic symptoms, but also recognizing graduations and overlaps between the two [START_REF] Angst | Classifi cation of schizo-affective patients by multidimensional scaling and cluster analysis[END_REF][START_REF] Gershon | A controlled family study of chronic psychoses. Schizophrenia and schizoaffective disorder[END_REF][START_REF] Kety | The concept of schizophrenia[END_REF]. [START_REF] Kendell | Diagnosis and classifi cation of functional psychoses[END_REF] claimed that the main problem was that the aetiology of psychotic disorders was not understood, therefore clinicians and researchers used the symptomatology to differentiate between psychotic disorders. However, the signifi cant degree of overlap between the symptomatology caused problems. Kendell (1987: 511) wrote, 'not one of them [psychotic disorders] is yet demarcated by its neighbours by clear boundaries. All are still defi ned by their clinical syndromes, and these syndromes merge imperceptibly into one another'.

In 1987 the revised edition of DSM-III was published (DSM-III-R) in an attempt to address the problems of reliability in using the criteria to reach a diagnosis. In the introduction to DSM-III-R, Spitzer and Williams (1987: xvii) wrote: Despite extensive fi eld testing of the DSM-III criteria before their offi cial adoption, experience with them since their publication had revealed, as expected, many instances in which the criteria were not entirely clear, were inconsistent across categories, or were even contradictory.

However, the revised edition did not address the issue of the validity of the diagnostic categories, and this remained problematic.

Many took issue with what they saw to be arbitrary categories. Ciompi (1984: 636) ironically declared that 'it seems obvious that there is a schizophrenia, since our psychiatric institutions are fi lled with patients with this diagnosis'. Richard Bentall, a British clinical psychologist, and colleagues concluded that '"schizophrenia" is not a useful scientifi c category and that for all these years researchers have been pursuing a ghost within the body of psychiatry' (Bentall, Jackson and Pilgrim, 1988a: 318). Yet despite criticizing the arbitrary nature of the classifi cations, most of these critics acknowledged the utility of diagnostic classifi cations. For example, William N. Goldstein, a psychodynamic-based psychiatrist argued that although DSM-III presented a reliable and straightforward method for making diagnoses and to structure research, this does not necessarily mean it is a true or good system [START_REF] Goldstein | DSM-III and the diagnosis of schizophrenia[END_REF]. Goldstein concluded:

DSM-III provides diagnostic criteria that are simply arbitrary. There is no reason to think that DSM-III is inherently better than DSM-I, DSM-II, Bleuler, or many other diagnostic systems. DSM-III should be accepted only as one system, among many, for making the diagnosis of schizophrenia … At the present time, when evaluating a patient for schizophrenia, DSM-III should be considered, but clearly not as the fi nal word. (p. 179) While a psychodynamic psychiatrist publishing in the American Journal of Psychotherapy might be expected to criticize the psychiatric approach, Brockington, a more traditional psychiatrist, expressed a similar sentiment. Writing in 1986, he agreed that 'schizophrenia' was just a classifi catory notion, grouping together patients who shared some symptoms and had a similar illness-course [START_REF] Brockington | Diagnosis of schizophrenia and schizoaffective psychoses[END_REF].

Robin M. Murray and Alice Foerster (1987) similarly argued that schizophrenia is useful as a provisional category, but that it may be abandoned in the future as the mechanisms of psychosis become better understood. While they acknowledged that the concept of schizophrenia could be mistaken, they still supported 'Kraepelin's view that both heredity and brain disorder are implicated [in psychosis]' (p. 138). Therefore, they suggested: 'perhaps in the near future we will be able to take our stance on the subdivision of psychosis according to aetiological principles rather than on the quicksands of symptomatology and course' (p. 138).

Although many criticized the Kraepelinian dichotomy, they suggested no alternative, and were forced to accept its utility in providing a common language for psychiatry and in shaping research and treatment. As Kendell (1987: 500) wrote:

The structure remains unchanged not because the rubrics concerned have been shown to represent valid and independent entities, but because no better classifi cation has yet been devised, and because we are aware that if the twin pillars of manic-depressive psychosis and schizophrenia are disturbed before there is anything better to put in their place the roof will come crashing in.

The 1980s can be seen as the decade when a new kind of scientifi c-based criticism to the Kraepelian model was introduced. This may have been partly due to the establishment of the more 'scientifi c' DSM-III model with which to disagree. That is to say that the concepts in themselves set up a situation where the criticism of them, in order to be effective, needed to be based on scientifi c grounds. Unlike much of the research quoted here, most of the literature discussing problems with the schizophrenia criteria during the 1980s failed to mention the diffi culties in separating it from bipolar disorder. Part of the reason for this may be the relative discrepancy between the volume of research on schizophrenia and bipolar disorder, with relatively little focus on bipolar disorder and its aetiology and symptomatology. This may have limited potential for understanding any similarities between the two disorders. Secondly, the dominant assumption that there were discrete disorders prevented many people from considering other models of psychosis seriously. Despite all the challenges to the dichotomy, Berrios and Hauser could still maintain in 1988 that it was a 'fact' that 'current psychiatry lives in a Kraepelinian world' (Berrios and Hauser, 1988: 813).

The 1990s: critiques and alternative approaches

By the 1990s, while there was still a sense that concepts such as schizophrenia provided an 'anchor from which developments can take place' (Venables, 1990: 203-4), criticisms of the dichotomy were growing, particularly regarding the reliability of the diagnostic categories. Kendell remained a key critic of the system into the 1990s. He declared in 1991:

For the last 20 years I have been dismayed by the widespread assumption that schizophrenia and manic-depressive illness are distinct diseases simply because we have given them different names … I have therefore tried again and again to convince my students and colleagues that these assumptions are unjustifi ed and that we must be prepared to consider other possibilities. (Kendell, 1991: 13) Kendell concluded that it might be that the Kraepelinian assumptions would turn out to be correct, and indeed that he would be pleased if they did. However, he asserted, there was not enough evidence to convince him that this was the correct conceptualization of psychosis [START_REF] Kendell | The major functional psychoses: are they independent entities or part of a continuum? Philosophical and conceptual issues underlying the debate[END_REF]. Although criticisms of the reliability of the diagnostic criteria for psychosis lessened during the 1990s, criticisms of the validity of the Kraepelinian dichotomy gathered force. A number of alternative approaches were proposed, building on a broad range of evidence.

Bentall has been one of the strongest advocates for abandoning the Kraepelinian dichotomy. Together with a number of other critics such as Mary Boyle and Theodore Sarbin, he put forward cases against schizophrenia (Bentall, 1990;[START_REF] Boyle | Schizophrenia: A Scientifi c Delusion?[END_REF][START_REF] Sarbin | Toward the obsolescence of the schizophrenia hypothesis[END_REF]. They subjected schizophrenia to scientifi c and historical scrutiny and argued that the concept of schizophrenia lacked scientifi c reliability and validity and thus should not form the framework for thinking about psychosis. Bentall edited a key volume in this debate entitled Reconstructing Schizophrenia (Bentall, 1990). In the preface he wrote that his intention was to reconsider the concept of schizophrenia afresh.

He argued that although the anti-psychiatrists of the 1960s and early 1970s claimed to be doing just this, their criticisms failed because they were based on poor and contradictory evidence (p. xiv). Bentall asserted: Some [critics] appeared to be rejecting scientifi c method or their ideas failed to convince many people working in the domain of mental health … This has led to the illusion that one is required to take one of two possible positions: either to accept the traditional account of psychiatric disorder (together with the forms of crude biological reductionism that inform it) or to reject an empirical approach to understanding madness altogether (throwing scientifi c reasoning out with the psychiatric bathwater in the process).

By explicitly differentiating himself from the much criticized anti-psychiatrists who rejected empirical methods, Bentall sought from the outset to place himself within the scientifi c community (Bentall, Jackson and Pilgrim, 1988b: 330). He proposed that schizophrenia is a hypothetical construct, and that psychosis would be better understood and treated by studying the specifi c symptoms of madness (Bentall, 1990). He claimed:

Serious questions remain about whether schizophrenia can be considered an illness; about whether it is one condition or several, about whether clear dividing lines can be found between schizophrenia and normal function or even between schizophrenia and other kinds of mental disorder. (Bentall, 1990: xiii) Similarly, Boyle, a clinical psychologist, rejected the schizophrenia concept on what she claimed were scientifi c grounds. She maintained that 'the concept of schizophrenia … has been developed and used in a way which bears little resemblance to the methods of construct formation used in medical and other empirical sciences' (Boyle, 1990: 193).

Charles G. Costello (1993a) argued that although it is important to investigate syndromes of schizophrenia, he agreed with Bentall that it may be more effective and advantageous to investigate specifi c symptoms. Nevertheless, Costello (1993b) asserted that while the symptom approach may be more fruitful than focusing on diagnostic categories, symptoms should not be considered in isolation, but rather in relation to all the other symptoms. He claimed that this symptom approach may eventually give rise to an understanding of typical symptom clusters that are the 'syndromes of schizophrenia' (Costello, 1993b: 300).

Reviewing the family and genetic studies from the 1980s, Crow (1991: 31) thought that the assumption that schizophrenia and bipolar disorder represent two distinct disease entities 'has been paralytic to our thinking and stultifying to research'. He rejected much of the evidence from family studies, arguing that the sample groups only included those who met the standardized criteria for bipolar disorder or schizophrenia and excluded schizoaffective cases, and therefore a conclusion that there is little overlap was more likely [START_REF] Crow | The failure of the Kraepelinian binary concept and the search for the psychosis gene[END_REF]. Instead, drawing on the studies, discussed above, which suggested that psychosis was likely to have a genetic basis and that there was an overlap between schizophrenia and bipolar disorder, Crow suggested that both disorders were affected by the same psychosis gene. He moved the discussion forward by claiming that there is an increased likelihood of psychotic patients within the same family being of the same sex and therefore proposed that the psychosis gene is located on the sex chromosome.

Recent developments in genetic research have also given support to this position. For example, overlapping genetic linkage regions for schizophrenia and affective disorders have been found [START_REF] Wildenauer | Do schizophrenia and affective disorder share susceptibility genes?[END_REF]. The authors argued that these overlaps suggest that a number of common genes may be involved in both these categories. On that basis, they concluded that the Kraepelinian dichotomy requires re-evaluation. [START_REF] Murray | The congenital and the adult-onset psychoses: Kraepelin lost, Kraepelin found[END_REF] agreed with Crow that the distinction between schizophrenia and psychotic affective disorder is fl awed, but they rejected Crow's explanations. Rather, they argued that the dividing lines between the disorders have been incorrectly drawn and that there are several different aetiological factors that affect the functional psychoses. Murray and O'Callaghan proposed dividing psychosis into congenital psychoses, which they considered to have resulted from abnormalities present at birth, and other psychoses that only arise during adulthood. They triumphantly asserted that they found 'no support for the current "Kraepelinian" distinction between manic-depression and schizophrenia' (Murray and O'Callaghan, 1991: 60) and that 'the pillars supporting the Kraepelinian dichotomy of the functional psychoses are crumbling' (Murray, O'Callaghan, Castle and Lewis, 1992: 326). But while they rejected the received view of the Kraepelinian dichotomy, they seemed unwilling to reject Kraepelinian ideas absolutely, claiming that 'the congenital psychoses closely resemble Kraepelin's original description of dementia praecox' (Murray and O'Callaghan, 1991: 60).

Other researchers proposed new ways of understanding the dichotomy. [START_REF] Cloninger | Pro: tests of alternative models of the relationship of schizophrenic and affective psychoses[END_REF] rejected both the discrete dichotomy model, and Crow's severity continuum model, arguing rather that schizophrenia and bipolar disorder should be considered as two discrete disease spectra which show some overlap at their extreme ends. [START_REF] Van Os | Risk factors for onset and persistence of psychosis[END_REF] argued that the studies on risk factors for psychosis suggest that there may be evidence for quantitative differences between schizophrenia and affective psychosis, but not for qualitative differences. They proposed:

A psychopathological continuum, with discrete effects working preferentially, though not exclusively, at particular ends of the continuum.

We suggest that there is a gradient both in terms of severity/prognosis and the magnitude of the effect of the risk factors, along dimensions of the continuum, rather than qualitative distinctions between categories. (p. 602; original italics).

Van Os et al. concluded that 'it may be time to pay more than lip service to the idea of a psychotic continuum, and to conceptually incorporate the notion in the way the search for the determinants, complications and treatments for psychosis is conducted ' (p. 603). Andreasen (1997: 108) conceptualized this interest in the full range of psychotic symptoms as 'coming back full circle' to the past work of people like Kraepelin himself, among others. It seems as if, like [START_REF] Murray | The congenital and the adult-onset psychoses: Kraepelin lost, Kraepelin found[END_REF], Andreasen was reluctant to distance herself entirely from Kraepelinian ideas.

In 1994 DSM-IV was published [START_REF] Apa | Diagnostic and Statistical Manual of Mental Disorders[END_REF]. It was based on a systematic review of the available scientifi c knowledge of psychiatric disorders, and was thus considered more empirical. However, [START_REF] Mccarthy | Revising psychiatry's charter document: DSM-IV[END_REF] examined the DSM-IV construction process and concluded that the revision functioned more as an attempt to give theoretical and scientifi c credibility to the biomedical model of psychiatry, rather than as a fundamental reconceptualization of mental disorders.

There still seemed many questions over the validity of the entities described in DSM-IV. Although in the preface it was claimed: 'there is no assumption that each category of mental disorder is a complete discrete entity with absolute boundaries dividing it from other mental disorders or from no mental disorder' (APA, 1994: xxii), it was later (p. 283) stated that 'much evidence suggests the importance of genetic factors in the aetiology of schizophrenia', demonstrating that it maintained the concept of schizophrenia as representing a natural disease entity.

By the end of the twentieth century, psychiatrists had generally come to agree that although the problems of reliability were addressed by DSM-IV, the validity of the diagnostic categories for psychosis was still problematic [START_REF] Craddock | The beginning of the end for the Kraepelinian dichotomy[END_REF][START_REF] Van Os | A comparison of the utility of dimensional and categorical representations of psychosis. UK700 Group[END_REF]. Ovsiew went so far as to say that, 'clinging to the idea, outmoded by biological data, that the classic clinical pictures represent distinct disease entities has been and continues to be a brake on progress.' The new challenge, he stated, 'is to devise diagnostic dimensions that have heuristic value for neuroscientifi c research and that can also guide clinical understanding and intervention' (Ovsiew, 2000: 298).

Retreating but not surrendering

Yet, despite the agreement that the dichotomy is fl awed, it still exists in the offi cial diagnostic systems. In 1995, European Archives of Psychiatry and Clinical Neurosciences published a special issue on the impact of Emil Kraepelin's concepts on world psychiatry. Jablensky, the guest editor of this issue, asserted that 'as clinicians and researchers, we today continue to operate in a Kraepelinian paradigm which started emerging nearly a century ago' (Jablensky, 1995: 186).

Kraepelin's ideas have remained infl uential, not because they are demonstrably 'true', but because they became paradigmatic within the fi eld of psychiatry. Psychiatric textbooks, offi cial diagnostic systems, psychiatric investigations and clinical treatments are still organized in a way that refl ected Kraepelinian assumptions about mental disorders [START_REF] Bentall | Madness Explained: Psychosis and Human Nature[END_REF]. The Kraepelinian dichotomy has retained its attraction for clinicians, because, as Craddock and Owen (2005: 364) write, it is 'conceptually simple and allows psychiatrists to demonstrate diagnostic expertise by exercising judgement over an often complex clinical picture and to reach a clear diagnosis'.

The dichotomy may also have been maintained because, even if potentially fl awed and 'in the absence of fully informed causal mechanisms' (Compton and Guze, 1995: 197), many have perceived it as an aid to research and treatment of psychosis. As Craddock and Owen (2005: 364-5) point out:

Kraepelinian diagnoses formed the basis of recent successes in genetics, probably because their net effect is to simplify the genetic architecture of the groups defi ned, albeit at the expense of excluding many cases. The dichotomy also formed the basis of the operational diagnostic criteria that brought a degree of rigour and reproducibility to psychiatric research. [START_REF] Compton | The neo-Kraepelinian revolution in psychiatric diagnosis[END_REF] note that the separation of manic-depressive psychosis from dementia praecox, enabled developments such as the specifi c treatment of bipolar disorder with lithium, and other antimanic agents. Also, despite many studies that have shown that the data do not fi t the traditional dichotomy, the proponents of the alternative approaches have not yet accumulated enough evidence to demonstrate that their method is better [START_REF] Craddock | The beginning of the end for the Kraepelinian dichotomy[END_REF]. [START_REF] Kuhn | The Structure of Scientifi c Revolutions[END_REF] argued that within any paradigm, anomalies will arise that cannot be explained. Generally anomalies are ignored or are explained as experimental errors. However, some anomalies are considered too signifi cant to ignore, and they push the paradigm into a state of crisis. Eventually a new paradigm emerges that deals with the anomalies, and this causes a paradigm shift. By the end of the twentieth century it was clear that there were signifi cant anomalies within the Kraepelinian paradigm, but it did not seem that psychiatry was in a state of crisis.

Part of the diffi culty with moving on from the Kraepelinian dichotomy is that it is diffi cult to understand how it might be done. This is partly due to the practical diffi culties of actually applying these concepts in a clinical setting [START_REF] Craddock | The beginning of the end for the Kraepelinian dichotomy[END_REF]. In Kuhnian terms, it may be that the lack of a viable alternative paradigm is a limiting factor in abandoning the Kraepelinian dichotomy. Psychotic symptoms are real phenomena, and clinicians need some kind of framework to conceptualize, investigate and treat these symptoms. As Hugh Freeman (2003: 32) concluded, 'mental health professionals must continue to practise the art of the possible … To abandon Kraepelin may also be to lose sight of clinical understanding.'

Conclusion

From the late 1970s, the neo-Kraepelinians actively reconstructed psychiatry around scientifi c and medical assumptions in order to fi ght off criticisms. The impact of the 'invisible college' of neo-Kraepelinians could be seen with the creation of DSM-III that contributed to the entrenchment of the Kraepelinian paradigm. With the construction of DSM-IV, this paradigm was fi rmly consolidated. During the 1980s these 'scientifi c' concepts met with a scientifi c criticism that challenged the Kraepelinian dichotomy, particularly regarding questions of the reliability of the diagnostic criteria in distinguishing between the two disorders. There were also a number of family studies that suggested that there was some overlap between genetic factors in schizophrenia and psychotic affective disorder.

During the 1990s, an increasing number of critics questioned the validity of the Kraepelinian paradigm. These critics gathered a signifi cant level of support, and many psychiatrists were prepared to acknowledge some of the issues. Yet, despite the acknowledgement of many clinicians that there are serious, if not fundamental, fl aws to the Kraepelinian dichotomy, this classifi catory distinction has not been formally abandoned. By the end of the 1990s it was generally accepted that psychotic symptoms occur, and that psychiatrists and psychologists needed new ways to delineate these symptoms, but no viable alternative paradigm for psychosis emerged by the end of the twentieth century. In 1988, Berrios and Hauser concluded that 'psychiatry still lives in a Kraepelinian world and its practitioners cannot escape the blinding embrace of its "episteme"' (Berrios and Hauser, 1988: 813). At the turn of the century, this was still the case.

Acknowledgements

This article is partly based on my dissertation for the MSc in History of Science, Technology and Medicine (2004-2005) organized by Imperial College London, University College London and the Wellcome Centre for the History of Medicine for which I received Wellcome Trust Funding. I would like to thank Michael Neve for his encouragement and supervision. I also want to thank the Medical Research Council for my current PhD funding at the Institute of Psychiatry, King's College London. Finally, I would like to thank Edgar Jones, Simon Wessely and Robin Murray for their comments on the paper.