Neurodevelopmental disorders represent a broad class of childhood neurological conditions that have a significant bearing on the wellbeing of children, families, and communities. In this review, we draw on evidence from two common and widely studied neurodevelopmental disorders—autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD)—to demonstrate the utility of genetically informed sibling designs in uncovering the nature and pathogenesis of these conditions. Specifically, we examine how twin, recurrence risk, and infant prospective tracking studies have contributed to our understanding of genetic and environmental liabilities towards neurodevelopmental morbidity through their impact on neurocognitive processes and structural/functional neuroanatomy. It is suggested that the siblings of children with ASD and ADHD are at risk not only of clinically elevated problems in these areas, but also of subthreshold symptoms and/or subtle impairments in various neurocognitive skills and other domains of psychosocial health. Finally, we close with a discussion on the practical relevance of sibling designs and how these might be used in the service of early screening, prevention, and intervention efforts that aim to alleviate the negative downstream consequences associated with disorders of neurodevelopment. Neurodevelopmental disorders are brain-based disorders of growth and development that have a significant impact on children's mental, emotional, and psychosocial health. Among the most common and widely studied neurodevelopmental disorders are autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder ADHD , 2). The. The2]). sibling design as any genetically informed design that capitalizes on a comparison or evaluation of traits in genetically similar individuals, including monozygotic or dizygotic twins, nontwin full siblings, or half-siblings.Given the individual, familial, and societal burden associated with neurodevelopmental disorders, there is a crucial need for methods of early detection to enable prevention programming prior to the emergence of fully fledged symptoms , 18. TheThe prevalence of ASD is estimated at around 1% of the population –21, withOver the last two decades, there has been a shift towards viewing ASD symptomatology along a quantitative spectrum as opposed to representing a discrete disorder . In this twin study, compares monozygotic (MZ) twins (who share 100% of their genetic information) to dizygotic (DZ) twins (who like nontwin siblings share 50% of their genes but like MZ twins share the same intrauterine environment). In a twin study, if the concordance rate among MZ twins is higher than that among DZ twins, then genetic influences are assumed. This is because the primary differences between MZ and DZ twins, aside from nonshared factors , are genetically mediated. Twin studies to date yield heritability estimates of ASD between 70 and 80% [The genetic pathophysiology of ASD is supported by three primary sibling-related designs. The first, called a and 80% –29. Asid and 80% ), these  and 80% . Also, t and 80% , 29.The presumed effect of genetic influences on development and behaviour is through endophenotypic variability in brain functioning and neurocognition . In termIn sum, these studies point to a strong genetic pathophysiology of ASD, and studies that link the genes involved in ASD to discrete brain circuits that support cognitive functions will prove critical in advancing our knowledge of these complex and as-yet unidentified mechanisms of development . recurrence rates in nontwin sibling pairs. These methods seek to determine the likelihood of an ASD diagnosis in the younger siblings of a child with an existing ASD diagnosis. Recent studies report that when followed from infancy to early childhood, the risk of developing ASD is between 10 and 20% for siblings of children with ASD compared to about 1% for siblings of a typically developing child [The second sibling approach to studying the etiology of ASD is to examineng child –38. Moreng child , 40. in utero environment is one of the foremost factors differentiating DZ from nontwin siblings, these findings again suggest that intrauterine factors, such as the elicitation of deleterious antibodies or differential recruitment of maternal resources, may represent additional sources of variability contributing to the risk of ASD. Indeed, a number of prenatal environmental agents have been linked to an increased risk of ASD, including maternal medications during pregnancy , maoic acid ), and pooic acid  and phthoic acid . To the oic acid , 47. In oic acid . prospectively track infants at risk for ASD, which is usually operationally defined as having an older sibling with ASD. By prospectively following high-risk infants, researchers can compare those that do and do not develop ASD to one another as well as to a control group . They can also compare siblings of children with ASD to the siblings of typically developing children on core neuropsychological, socioemotional, and behavioural traits to identify early markers of ASD. It is also possible to track the trajectories of children at risk of ASD to ascertain long-term neurodevelopmental outcomes and whether early behavioural markers are associated with later diagnostic classification.The third stream of research utilizing sibling designs are those thatStudies tracking siblings at risk of ASD have shown that the extent of their early difficulties is predictive of later social and behavioural problems and may also differentiate them from the siblings of typically developing children. For instance, in siblings of children with ASD, initial levels of joint attention (at 15 months) predicted the extent of social impairment and ASD diagnosis at 34 months  as well Perhaps the greatest benefit of prospective studies of siblings of children with ASD is to determine the temporal onset of cognitive/behavioural problems in children who themselves go on to develop ASD. These infant sibling studies have revealed reliable differences in language , orientiStudies employing sibling-based designs in the study of ASD have expanded our knowledge of the genetic epidemiology of the disorder and also help to clarify how genes and environments may operate in tandem in the pathogenesis of neurodevelopment. Twin designs suggest a high genetic contribution to ASD, a finding that is now well established. Further, research examining recurrence risk of ASD (either in twin or in nontwin siblings) suggests that not only is the degree of genetic relatedness associated with risk of ASD, but also environmental exposures may epigenetically regulate the expression of genes that modulate ASD symptomatology. In this regard, the joint circumstance of genetic vulnerability alongside exposure to teratogenic or neurotoxic agents may particularly predispose children to poor neurodevelopmental outcomes. Moreover, sibling studies that prospectively track infants have been useful in elucidating early markers of not only the risk of future ASD diagnosis, but also the risk of discrete neuropsychological skill deficits in the absence of ASD classification. The latter finding suggests that siblings of children with ASD may benefit from early prevention and monitoring.While our knowledge of overall genetic and symptom risk related to ASD has been fostered by sibling studies, there remain gaps in our understanding of the discrete molecular genetic variants that create vulnerability to ASD among siblings, as well as how variability in neural functioning serves as an endophenotypic link between genetic risk and behavioural manifestations of the disorder. Future research in this area that compares MZ, DZ, nontwin full siblings, and half-siblings will shed light on whether the apparent gradient relationship between degree of genetic relatedness and risk of ASD also applies to cognitive processing and neural functioning that supports the behavioural and social-emotional faculties associated with ASD.ADHD is the most common childhood neurodevelopmental disorder, affecting approximately 5% of school-age children . These pADHD has an overlapping yet distinct neurocognitive profile to ASD . Despiteh2 = .75 to .91), whether defined according to strict clinical cut-offs or along a broad phenotypic continuum [Twin studies suggest that heritability of ADHD is high , and exposure to stress hormones are also operative [Although genetic factors are highly implicated in the etiology of ADHD, environmental factors such asperative , 94–98. perative , 7.Compared to the siblings of non-ADHD controls, siblings of children with ADHD who themselves go on to develop ADHD have been shown to demonstrate more neuropsychological difficulties in the areas of attention, executive functioning, and memory . In the Finally, it is interesting to note that familial risk of neurocognitive impairment not only is observed in twin studies (see above), but also has been reported in the nontwin siblings of children with ADHD. For instance, there is evidence that children with ADHD and their unaffected siblings demonstrate volume and/or activity reductions in prefrontal, occipital, and parietal regions compared to controls . FurtherSibling research into ADHD suggests that this relatively common neurodevelopmental disorder is highly heritable and that subclinical or associated impairments may be present in the siblings of children with ADHD, even if a full-blown ADHD diagnosis is not warranted. Compared to research on ASD, the relative paucity of literature using sibling-based designs for ADHD provides important opportunities for future research.Although early biological and behavioural manifestations of ADHD may have important implications for long-term outcomes , there a not have an ASD diagnosis and found that children with ADHD who had higher levels of autistic symptomatology were more impaired in terms of severity of ADHD and various other domains of psychopathology and cognition. Notably, greater severity in comorbidities was seen after accounting for ADHD symptomatology, suggesting that elevation was related to characteristics of autism rather than being driven by severity of ADHD itself.Although neurodevelopmental disorders are demarcated as discrete categories in the DSM-5 (in addition to earlier versions), emerging theoretical models and empirical evidence suggest a high degree of overlap between them. A recent review concluded that the cooccurrence of these disorders is high, with studies showing that 20–50% of children with ADHD display variable symptoms of ASD and 30–80% of children with ASD meet criteria for ADHD . RecentlWith respect to sibling designs specifically, twin studies suggest a moderate degree of overlap in genetic influences on ASD and ADHD traits, whether in the general population or in samples with clinically elevated symptoms –122. In Currently, sibling studies examining the occurrence of autism symptoms in children with ADHD show that ASD symptoms are more prevalent in children with ADHD than controls. For example, Mulligan et al.  examinedFor instance, Rommelse et al.  showed tIn sum, these varied studies using sibling methodology suggest that not only are ASD and ADHD related through common heritable factors, and perhaps relatively less strongly through environmental conditions, but also there may be specific symptoms that show overlap. Uncovering whether the nontwin siblings of children with particular ASD and ADHD traits also demonstrate increased crossover vulnerability to specific neurocognitive problems using prospective tracking designs is a ripe area for future research.Taken together, the value of studying the siblings of children with neurodevelopmental conditions such as ASD and ADHD is the ability to (i) determine the relative contribution of genetic and nongenetic factors using twin designs; (ii) quantify the risk of development of these conditions by examining recurrence rates in siblings compared to control siblings or population prevalence rates; (iii) determine whether subclinical impairments in endophenotypes are present, such as social communication, executive functioning, and language, in the siblings of children with neurodevelopmental conditions; (iv) ascertain the risk of other cooccurring psychological/psychiatric conditions; (v) examine the developmental onset of various problems in at-risk siblings by prospectively tracking them and determining when early manifestations of these difficulties first emerge; (vi) identify potential moderating factors that serve to protect children showing early manifestations of difficulties; and (vii) understand the nature of comorbidity and symptom overlap of neurodevelopmental disorders, including how nonspecific neurocognitive traits contribute to various disorders and which neurocognitive traits are explained by common genetic and/or environmental factors. On aggregate, these findings point to a need for appropriate prevention programs in order to reduce the risk of later problems.Clinically, the ability to identify children at risk of later difficulties  enables researchers, clinicians, and policymakers to determine who to target for primary prevention given scant societal resources. We know from the above studies that siblings of children with ASD and ADHD represent a subpopulation of children who are vulnerable to suboptimal social, emotional, cognitive, and psychiatric outcomes. We also know that, for ASD in particular, while differentiation of siblings who experience later problems within the first year of life is difficult, there is a constellation of phenotypes that emerge after 12 months that may be key markers of later difficulties. Importantly, there does not appear to be a single atypical behaviour that reliably predicts later neurodevelopmental problems . Rather,Prospective studies , 60, 61 Access to early intervention services for those determined to be at risk, by virtue of their family history, genetic disposition, and/or early assessment, is critical to alleviating the burden of neurodevelopmental morbidity on children, families, and society. However, the current state of services for infants and toddlers suspected to have these conditions is limited. Fostering the ability of parents and caregivers to respond sensitively and contingently may be particularly useful for children's emotional, social, and cognitive development , an effeDelineating early markers of the emergence and persistence of ASD and ADHD through sibling studies has implications for preventive and early intervention efforts. Infancy and early childhood represent a time of heightened neurobiological sensitivity  and thus interventions during this period may have a lasting impact. Additionally, early intervention may serve to derail the onset of maladaptive behavioural patterns associated with symptomatology  and can also support families prior to the formation of negative assumptions and attitudes associated with full symptomatology.Specific examples of intervention programs for children at risk of neurodevelopmental disorders, defined as being a younger sibling of a child with a neurodevelopmental disorder, are sparse. In fact, we know of none for children at risk of ADHD and could identify only a handful of intervention studies for children at risk of ASD. Three of these were small studies with less than 10 participants: one was a case series of seven siblings of children with ASD , while tOur understanding of neurodevelopmental disorders has increased dramatically over the last four decades, and sibling designs have been instrumental in elucidating the complex and heterogeneous pathways to neurodevelopmental functioning. Twin, recurrence risk, and prospective tracking studies have not only improved our understanding of the etiology of neurodevelopmental conditions but also bolstered our capacity to identify children at risk of particular conditions in order to effectively intervene before the emergence of stable and severe levels of difficulty requires costly remediation. Findings from high-risk sibling studies may thus serve to inform universal screening procedures that could be implemented in primary care settings. These studies could, for example, aid in the development of a risk index that reliably identifies children who could be effectively targeted with early intervention approaches . Once id


Haemadipsa rjukjuana, the first recorded sanguivorous land leech in the Republic of Korea (ROK).Leeches can transmit pathogens and are therefore potentially hazardous to human and animal health. However, only a few studies of diseases transmitted by land leeches have been reported. The purpose of the present study was to analyse which pathogens are carried in H. rjukjuana were collected from Mt. Dock-Sil on Gageo-do Island, ROK during July 2011. Conventional PCR was conducted for analysis of the origin of blood meal, as well as for detection of species of Anaplasma, Bartonella, Borrelia, Ehrlichia, Rickettsia, and Wolbachia in the leech specimens. Bartonella DNA was detected in eight of the specimens studied based on partial ITS sequence analysis. Seven of the DNA samples were closely related to Bartonella grahamii (99.6–100 % similarity), and one sample exhibited a 90.6 % similarity with Bartonella sp. from Taiwan. Sequences of the mitochondrial cytochrome b gene were generated for a total of 35 of the 173 leech internal organ samples. These included sequences of human (n = 10), mouse (n = 8), weasel (n = 6) and bird (n = 11) origin. Of these 35 sequences, 68.5 % were from mammals, including humans, and 31.4 % were from migratory birds that pass through Gageo-do, ROK.A total of 173 Bartonella species to hosts directly, to our knowledge this is the first report on Bartonella DNA being detected from leeches. Therefore, further studies are needed to explore the possibility of zoonotic pathogen transmission by land leeches.Although the present study does not provide evidence that leeches indeed transmit  Hirudo medicinalis may bring about severe diseases by transmitting infectious agents that cause syphilis , erysipelas (Streptococcus sp.), tetanus (Clostridium tetani), hog cholera (hog-cholera virus), and hospital wound infection (Aeromonas hydrophila) [Ozobranchus (turtle leech) may be a mechanical vector for the fibropapilloma-associated turtle herpesvirus [Rickettsia infection was detected in Torix tagoi, Torix tukubana and Hemiclepsis marginata [The possibility that leeches can be vectors of pathogens has been studied in the more recent past, especially with the advent of leech therapy. The medical leech, rophila) –4. Besidpesvirus  and thatarginata . These rarginata . Becausearginata .Haemadipsa rjukjuana (Hirudiniformes: Haemadipsidae) was identified as the first reported sanguivorous land leech in the Republic of Korea (ROK) [H. rjukjuana and of its blood meal was conducted by PCR assay. The terrestrial leeches were screened for the presence of Anaplasma phagocytophilum, Anaplasma bovis, Ehrlichia chaffeensis, Ehrlichia canis, Borrelia burgdorferi, Bartonella spp., Rickettsia spp. and Wolbachia spp. DNA by using a set of species-specific primers. For blood meal screening, the mitochondrial cytochrome b gene was used to amplify host blood DNAs from the internal organs of H. rjukjuana collected in the field.In previous studies, ea (ROK) , 10. Memea (ROK) . In thisBartonella spp., A. phagocytophilum, A. bovis, E. chaffensis, E. canis, B. burgdorferi, Rickettsia spp. and Wolbachia spp. were PCR amplified. For analysis of the host animals, the mitochondrial DNA cytochrome b gene was amplified by conventional PCR. The primers used for PCR amplification are listed in Table Bartonella spp. are shown in Fig. A total of 173 terrestrial leeches were collected at Mt. Dock-Sil  in Gageo-do (Island), Shinan-gun, Jeollanam-do (Province), ROK  from a wild rodent in Taiwan. Among the seven B. grahamii sequences, two were closest to B. grahamii KWDBG 41  from Apodemus agrarius , and the other five samples were identical with B. grahamii V2 (AJ269785). As a result, the sequences of B. grahamii obtained in this study were divided into two sub-clades. One sub-clade included the V2 isolate from the United Kingdom (AJ269785) and one Korean genotype (JN810847) and the other sub-clade included another Korean genotype (JN810843) , mouse (n = 8), weasel (n = 6), pale thrush (n = 3), grey-backed thrush (n = 3), rufous-tailed robin (n = 1), Siberian rubythroat (n = 1), oriental magpie robin (n = 1), black-faced bunting (n = 1) and yellow-throated bunting (n = 1) DNA sequences were detected . The 16S-23S ITS region of Bartonella spp. was chosen for the PCR amplification, being a useful genetic marker to identify this species because of its hyper-variable sequences and much lower sequence similarity than other target genes [Most vector-borne diseases, including dengue, Lyme disease, malaria, endemic typhus, and bartonellosis are transmitted by sucking arthropods such as fleas, mosquitoes and ticks . Leech isia spp. , 7. In tet genes .Bartonella spp. are small, gram-negative bacteria that infect red blood cells and invade endothelial cells, and are infective to hosts or reservoirs. Several Bartonella spp. are identified as zoonotic agents causing cat scratch disease, bacillary angiomatosis, neuroretinitis, etc. [Bartonella have been detected or cultured from numerous arthropods, various arthropods have been explored as potential vectors for this bacterial species [Ixodes ricinus may serve as a competent vector for Bartonella spp. suggesting a potential new vector [is, etc. . Because species , with tiw vector , 19. HowBartonella spp. also have a natural cycle that comprises a vector and a host as other pathogens. Although our data was only represented the molecular evidence of Bartonella in leeches, we think that leech may serve as a host for Bartonella species. In addition to the record of Bartonella spp., a study of the blood meal is very important toward understanding the host preferences and vector capacity of leeches. Furthermore, blood meal is commonly used to investigate the distribution of hosts and to control disease spreading [B. grahamii. This finding indicates that these leeches are likely to carry the blood of animals and thereby disperse several pathogens.preading , 20. In Because Gageo-do is an isolated island far from the mainland Fig. , the mamBartonella spp. transmission. Although it does not prove that leeches indeed transmit the bacteria to the hosts, to our knowledge, this is the first report of Bartonella DNA being detected from leeches. The vector competence is completed when the zoonotic agent is transferred from the vector to the host reliably, and vertical or horizontal transmission should be possible [Our study provided new data on the potential role leeches may play in possible , 17. TheDNA, deoxyribonucleic acid; ITS, internal transcribed spacer; PCR, polymerase chain reaction; ROK, Republic of Korea


Attention deficit hyperactivity disorder (ADHD) is a lifelong condition which carries great cost to society and has an extensive comorbidity. It has been assumed that ADHD is 2 to 5 times more frequent in boys than in girls. Several studies have suggested developmental trajectories that link ADHD and certain personality disorders. The present study investigated the prevalence of ADHD, common Axis I disorders, and their gender differences in a sample of adolescent outpatients. We also wanted to investigate the relationship between ADHD and personality disorders (PDs), as well as how this relationship was influenced by adjustment for Axis I disorders, age and gender.We used a sample consisting of 153 adolescents, aged 14 to 17 years, who were referred to a non-specialized mental health outpatient clinic with a defined catchment area. ADHD, conduct disorder (CD) and other Axis I conditions were assessed using the Mini International Neuropsychiatric Interview (MINI). PDs were assessed using the Structured Interview for DSM-IV Personality (SIDP-IV).p = 0.001), and this relationship was not significantly weakened when adjusted for age, gender and other Axis I disorders (p = 0.026). Antisocial  and borderline  PDs were significantly more frequent in girls than in boys with ADHD.13.7 % of the adolescents met diagnostic criteria for ADHD, with no significant gender difference. 21.6 % had at least one PD, 17.6 % had CD, and 4.6 % had both ADHD and a PD. There was a significantly elevated number of PD symptoms in adolescents with an ADHD diagnosis (We found no significant gender difference in the prevalence of ADHD in a sample of adolescents referred to a general mental health outpatient clinic. Adolescent girls with ADHD had more PDs than boys, with antisocial and borderline PDs significantly different. The present study suggests that ADHD in girls in a general outpatient population may be more prevalent than previously assumed. It especially highlights the importance of assessing antisocial and borderline personality pathology in adolescent girls presenting with ADHD symptoms. Attention deficit hyperactivity disorder (ADHD) is a common and often lifelong condition which carries great cost to society and has an extensive psychiatric comorbidity –4. It maThe worldwide prevalence of ADHD has been estimated at about 3–5 % , 8, but ADHD is generally considered to be more prevalent in boys than in girls, with male/female ratio estimates ranging from 2:1 to 9:1 , 12. HowADHD has been associated with anxiety, mood, and disruptive behavioral disorders . In a saIn DSM-IV and DSM-5, personality disorder (PD) categories may be applied to adolescents when the individual’s particular maladaptive personality traits are pervasive, persistent, and unlikely to be limited to a particular developmental state or an episode of an Axis I disorder. With the exception of antisocial PD (ASPD), any PD can be diagnosed in a person under 18 years of age if the diagnostic features have been present for at least 1 year , 16. HowPDs are common, with adult prevalence numbers of 10–15 % in the general population , up to 4Research supports the assumption that PD symptoms emerge at an early age and are related to health-risk behaviors in adolescence as well as young adulthood –24, but Borderline PD (BPD) has a lifetime prevalence of 2.7 % in the general population; it seems to be equally prevalent among men and women . DiagnosFew studies have reported on gender differences  and gendThe question has been posed if ADHD can be considered an early stage in the development of BPD. A comprehensive literature review found data that provide a basis for the hypotheses that ADHD is either an early developmental stage of BPD, or that the two disorders share an environmental and genetic aetiology .Adults with severe BPD frequently show a history of childhood ADHD symptoms. Persisting ADHD correlates with the frequency of co-occurring Axis I and PDs –41; for In prisoners childhood and adult ADHD symptoms were found to be positively correlated with BPD and negatively correlated with compulsive personality pathology. Axis I disorders were not significantly related to childhood ADHD . A studySeveral studies have suggested developmental trajectories that link ADHD, bipolar disorder and certain PDs, especially BPD. The exact nature of these aetiological links is not known , 46, butSperanza and colleagues found comorbid ADHD to influence the clinical presentation of adolescents with BPD, and that comorbid ADHD was associated with higher rates of disruptive disorders, with a trend towards a greater likelihood of cluster B PDs and with higher levels of impulsivity, especially of the attentional/cognitive type . Prada aIndividuals diagnosed with childhood ADHD were found to be at increased risk for PDs in late adolescence, specifically borderline (OR = 13.16), antisocial (OR = 3.03), avoidant (OR = 9.77), and narcissistic (OR = 8.69) PDs. Those with persistent ADHD were at higher risk for antisocial (OR = 5.26) and paranoid (OR = 8.47) PDs but not the other PDs, when compared to those in whom ADHD remitted. These results suggest that ADHD portends risk for adult PDs, but that the risk is neither uniform across disorders, nor uniformly related to child or adult diagnostic status .Females with ADHD and BPD seem to share more clinical features than males , 51; in Investigate the prevalence of ADHD and common Axis I disorders, including possible gender differences.Investigate the relationship between ADHD and PDs. We also wanted to assess the influence of adjusting for Axis I disorders, age and gender on the relationship between ADHD and PDs.The objective of the present study, performed on a clinical sample of consecutively referred adolescent outpatients, was toThe sample consisted of adolescents aged 14–17 years who were referred to a mental health outpatient clinic for children and adolescents in Oslo . The Nic Waal Institute is serving four city districts with a population of mixed socioeconomic status, representing all social classes including immigrant workers and well-educated middle and upper class families. The catchment area comprises a total population of 25, 000 children and adolescents from 0 to 17 years of age.Study inclusion took place from February 2005 to April 2007. Exclusion criteria were the need for immediate hospitalization or other urgent therapeutic measures, clinically assessed mental retardation, lack of fluency in the Norwegian language, and absence of the evaluator at the time of referral.A primary screening for ADHD was performed using the six-item Adult ADHD Self-Report Scale Screener version 1.1 (ASRS Screener) in a Norwegian translation . The ASRIf the primary screening with the ASRS Screener was positive, the Mini International Neuropsychiatric Interview-PLUS (MINI-PLUS) section W (ADHD in children/adolescents) was used as a diagnostic test instrument  for a fiThe Mini International Neuropsychiatric Interview version 5.0.0 (MINI) in a Norwegian translation was used for assessing Axis I disorders , 58.The Structured Interview for DSM-IV (SIDP-IV)  in a NorAll questions address the typical or habitual behaviour of the subjects during the last 5 years. Each diagnostic criterion is rated on a four point scale: “0” = criterion not present; “1” = subthreshold level of the trait present; “2” = criterion being present for most of the last 5 years; and “3” = criterion strongly present. Scores “2” and “3” indicate the presence of a criterion according to DSM-IV .In accordance with diagnostic practice applied in other studies on PDs in adolescence, the DSM-IV age criterion for ASPD was waived . Due to The first author assessed all participants. The parents or other legal guardians were not involved in the assessment process. The evaluator, male M.D., with 21 years of clinical experience, was specialist in psychiatry and child and adolescent psychiatry. He was trained in evaluation with SIDP-IV by the second author, who was an experienced rater, who had previously evaluated patients and reported from comparable studies , 63. TweAfter completion of the initial assessment, the patients were assigned to further clinical evaluation and treatment by clinicians other than the evaluator in the outpatient clinic.Descriptive statistics were calculated for the relevant mental health status variables and expressed in mean (SD) and frequency (%) as appropriate. Prevalences of ADHD, other Axis I conditions and PDs with 95 % Blaker confidence intervals  were esta 95 % confidence intervals based on 10 000 bootstrap replicates [Adjustment for age and Axis I disorders was not performed due to the low number of degrees of freedom available. However, the relationship of the number of PD symptoms with ADHD symptoms, unadjusted and adjusted for gender, age and important Axis I disorders  was investigated by linear regressions wherein multicollinearity was checked by variance inflation factor (VIF), preferably below 5–10 for all covariates. Differences in unadjusted and adjusted odds ratios and regression coefficients were, when necessary, investigated by a bootstrap BCplicates , with a Data were analysed using the IBM SPSS version 20.0 software, with Blaker confidence intervals computed in the R  package BlakerCI and bootstrapping in the R package boot. Graphical investigations also used R.N = 94) girls were included in the study. There were no missing data on MINI and SIDP-IV. The flowchart in Fig. A total of 153 adolescents; mean age 16.0 years , 61.4 % (N = 50) initially screened positive for ADHD using the ASRS Screener. When using the MINI-PLUS as a diagnostic instrument, 13.7 %  of the adolescents fulfilled all diagnostic criteria for ADHD according to DSM-IV, with no significant gender difference in prevalence . The male/female ratio was 1.19 (95 % CI = 1.12–1.30). The distribution of hyperactivity/impulsiveness and inattention symptoms in different Axis I conditions can be seen in Fig. When analysed separately for hyperactivity/impulsiveness and inattention symptoms in each gender, girls had slightly higher overall symptom scores than boys, but the difference was not significant  of the adolescents met the criteria for at least one Axis I disorder . There were 16 boys (27.1 %) and 40 girls (42.6 %) with more than one Axis I disorder apart from ADHD (p = 0.060). Anxiety disorders; simple phobias, generalized anxiety disorder, panic disorder, agoraphobia, social phobia and post-traumatic stress disorder  and mood disorders; dysthymia and major depressive episode  were most frequent, followed by substance-related disorders; alcohol and drug abuse or dependence , CD , obsessive-compulsive disorder  and psychotic disorders . There were significant gender differences in anxiety (p = 0.022) and mood (p = 0.033) disorders. There were no bipolar, anorectic or bulimic patients in the sample  had at least one PD, 7.2 % (N = 11) had more than one PD, and 4.6 % (N = 7) had both ADHD and a PD. The prevalence of PDs was generally higher in the referred girls. As shown in Table p = 0.002) and BPD (p = 0.042), as well as between ADHD and CD (p = 0.003). Only 3.4 % (N = 2) of boys and 3.2 % (N = 3) of girls, all with ADHD, matched the criteria for ASPD. There was no significant relationship with any other PDs , depressive PD (p = 0.020), anxiety disorders (p = 0.022), and mood disorders (p = 0.033). ASPD (p = 0.409), avoidant PD (p = 0.487), substance use disorders (p = 0.831), and CD (p = 0.585) did not yield significant gender differences.An illustration of the relationship between ADHD symptoms and relevant Axis I conditions and PDs is shown in Fig. p = 0.164) nor when adjusted for gender . No bootstrap procedure was considered necessary since these confidence intervals overlapped almost completely. Also, in unadjusted analysis the number of PD criteria was significantly higher  when ADHD diagnosis was present. In analysis adjusted for gender, age and Axis I disorders the corresponding estimate was 9.6, 95 % CI 1.2–18.0, p = 0.026. There was no significant difference between the unadjusted and adjusted estimate (95 % CI −0.52–13.43).There was no significant relationship between ADHD diagnosis and at least one PD, neither in unadjusted analysis  and mood (p = 0.033) disorders, with girls having the highest prevalence.More than two thirds of the adolescents met the criteria for at least one Axis I disorder, with anxiety and mood disorders being most frequent. There were significant Axis I gender differences only in anxiety . When adjusted for age, gender and other Axis I disorders, this relationship was still significant (p = 0.026). Hence, the present study suggests that by using reliability-tested diagnostic interviews like the SIDP-IV, it is feasible to assess PDs in adolescents with ADHD, also in the presence of one or more comorbid Axis I disorders.The limited data size did not permit us to investigate the relationship between ADHD and single PDs. We did, however, find a significantly elevated number of PD symptoms in adolescents with an ADHD diagnosis (N = 48) and the relatively small sample size constitute limitations. In particular, a limited number of degrees of freedom prevented the inclusion and investigation of interactions of potentially important adjustment variables like ADHD subtype. The participants were included in a limited time span, and we do not know if there were prevalence fluctuations over time.The study was performed at a single general service mental health outpatient clinic, receiving adolescents from a geographically defined urban area of varied socioeconomic and ethnic population. However, the results from the present study may not be generalizable to other populations. The attrition (23.9 %, The gender distribution of our sample was close to identical to the gender distribution of all referred adolescents in the study inclusion period, and reflects the fact that more adolescent girls than boys are referred to Norwegian mental health outpatient clinics.Each patient was diagnosed individually with well-documented semi-structured interviews by a single, experienced clinician and rater. The MINI-PLUS, which utilizes the DSM-IV diagnostic criteria in a strict manner, was used for diagnosing ADHD. This was considered advantageous, as we did not want to overestimate the prevalence. The evaluator was trained in rating with SIDP-IV and MINI by experienced evaluators and researchers on PD and Axis I diagnoses. Still, the use of a single evaluator constitutes a possible limitation. This may have strengthened the internal validity, but might have been a threat to the external validity of the diagnoses.ADHD is an often lifelong condition with an extensive psychiatric comorbidity , 3.It has been assumed that ADHD is 2 to 5 times more frequent in boys than in girls , 8. We dGirls with ADHD were more severely ill than boys with ADHD; we found higher PD prevalences for girls, with significant differences for ASPD and BPD. All girls with ASPD met the diagnostic criteria for ADHD.The present study suggests that ADHD in girls in a general outpatient population may be more prevalent than previously assumed. It especially highlights the importance of assessing antisocial and borderline personality pathology in adolescent girls presenting with ADHD symptoms.


While the negative association between ADHD symptoms and IQ is well documented, our knowledge about the direction and aetiology of this association is limited. Here, we examine the association of ADHD symptoms with verbal and performance IQ longitudinally in a population-based sample of twins. In a population-based sample of 4,771 twin pairs, DSM-IV ADHD symptoms were obtained from the Conners’ Parent Rating Scale-Revised. Verbal (vocabulary) and performance (Raven’s Progressive Matrices) IQ were assessed online. ADHD symptom ratings and IQ scores were obtained at ages 12, 14 and 16 years. Making use of the genetic sensitivity and time-ordered nature of our data, we use a cross-lagged model to examine the direction of effects, while modelling the aetiologies of the association between ADHD symptoms with vocabulary and Raven’s scores over time. Although time-specific aetiological influences emerged for each trait at ages 14 and 16 years, the aetiological factors involved in the association between ADHD symptoms and IQ were stable over time. ADHD symptoms and IQ scores significantly predicted each other over time. ADHD symptoms at age 12 years were a significantly stronger predictor of vocabulary and Raven’s scores at age 14 years than vice versa, whereas no differential predictive effects emerged from age 14 to 16 years. The results suggest that ADHD symptoms may put adolescents at risk for decreased IQ scores. Persistent genetic influences seem to underlie the association of ADHD symptoms and IQ over time. Early intervention is likely to be key to reducing ADHD symptoms and the associated risk for lower IQ. Attention-deficit/hyperactivity disorder (ADHD) is associated with lower mean IQ scores. The correlation between IQ and ADHD symptoms reported in general population samples ranges from—0.2 to—0.4 ,2. A metIn a clinical sample, children with IQs < 70 showed more severe ADHD symptoms than children with IQ > 70 . Lower IA = -0.45 between IQ and ADHD symptoms and rA = -0.59 between IQ and ADHD research diagnosis  (s theory . Estimats x100)] .Cross-lagged effects: The model specifies the across-time correlations by means of causal cross-lagged paths, which connect different measures across time points . To examine the changes in genetic and environmental aetiologies of the association between ADHD symptoms and IQ, the covariance between ADHD symptoms and IQ was divided into covariance specific to t2 or t3 and covariance shared with the previous time point.In order to establish the extent to which the same or different aetiological factors influence ADHD symptoms and IQ over time, genetic and environmental variances were divided into variance specific to t2 x b112 . VariancThe phenotypic across-trait correlations between ADHD symptoms and vocabulary scores ranged from -0.16 to -0.24 . The pheA1 = -0.29, rA2 = -0.31, rA3 = -0.20; 1, t2 and t3, 74%, 61% and 50% of the phenotypic correlation between ADHD symptoms and vocabulary scores were attributable to genetic influences, respectively  and vocabulary scores  were significant and moderate to high (2—test indicated that the cross-lagged path from ADHD symptoms at t1 to vocabulary scores at t2 (b12 = -0.14) was significantly larger than the cross-lagged path from vocabulary scores at t1 to ADHD symptoms at t2 . The cross-lagged path from ADHD symptoms at t2 to vocabulary scores at t3 (b34 = -0.10) was not significantly different from the cross-lagged path from vocabulary scores at t2 to ADHD symptoms at t3 . Analyses of the relationship between vocabulary and inattention scores, and the relationship between vocabulary and hyperactivity-impulsivity scores, revealed the same pattern as above for both symptom dimensions (not presented here).The stability paths of ADHD symptoms  and Raven’s scores  were similarly significant and moderate to high (2—test indicated that the cross-lagged path from ADHD symptoms at t1 to Raven’s scores at t2 (b12 = -0.10) was significantly larger than the cross-lagged path from Raven’s scores at t1 to ADHD symptoms at t2 . The cross-lagged path from ADHD symptoms at t2 to Raven’s scores at t3 (b34 = -0.08) was not significantly different from the cross-lagged path from Raven’s scores at t2 to ADHD symptoms at t3 . Analyses of the relationship between Raven’s and inattention scores, and the relationship between Raven’s and hyperactivity-impulsivity scores, revealed the same pattern as above for both symptom dimensions (not presented here).In the cross-lagged model of the association between ADHD symptoms and Raven’s scores, the stability paths of ADHD symptoms  association of ADHD symptoms with vocabulary and Raven‘s scores at t1 to t2 and from t2 to t3. However, ADHD symptoms at t1 were a significantly stronger predictor of both vocabulary and Raven’s scores at t2 than vice versa. No differential effects emerged for the cross-lagged paths from ADHD symptoms at t2 to vocabulary or Raven’s scores at t3 and vice versa. The lack of differential effects may be explained by the fact that the direct effects of ADHD symptoms at t2 on vocabulary or Raven’s scores at t3 and vice versa are likely attenuated by the indirect effects from the associations at previous time points . The developmental patterns for the association of ADHD symptoms with these two IQ subscales were highly comparable.Thirdly, ADHD symptoms and vocabulary scores, and ADHD symptoms and Raven’s scores, significantly predicted each other from tThe cross-lagged effects are small, as is common ,35–37, bOne way in which ADHD symptoms may affect IQ scores is through education: the core symptoms of ADHD—inattention, impulsivity and hyperactivity—may lead to difficulties in following teachers’ instructions and lesson content and, thus, interfere with opportunities to benefit from education. Data from the prospective, population-based Avon Longitudinal Study of Parents and Children n = 11,640) show that parent-rated hyperactivity and inattention symptoms measured at age 3 had negative effects on academic outcomes at age 16 . Further show thaThe study has some limitations. We investigated the association between ADHD symptoms and IQ in a population-based sample of twins rather than a clinical sample. The associations of ADHD symptoms with VIQ and PIQ are likely to be greater and may differentiate in individuals diagnosed with ADHD ,4. HowevThese limitations notwithstanding, the prospective developmental design of our cross-lagged analysis allowed us to explore the direction of effects for the negative association between ADHD symptoms and IQ scores, as well as the dynamic and stable nature of the aetiological influences on these variables and their association. ADHD symptoms and IQ scores significantly predicted each other over time. Yet, ADHD symptoms at age 12 years were a significantly stronger predictor of both vocabulary and Raven’s scores at age 14 years than vice versa. Time-specific aetiological influences emerged for each trait. However, the aetiological factors involved in the association between ADHD symptoms and IQ were highly stable over time. Future research will need to build on these results to investigate how early intervention targeting ADHD symptoms may aid in reducing the risk for lower IQ.S1 Dataset(CSV)Click here for additional data file.


Cross-cohort comparison is an established method for improving causal inference. This study compared 2 cohorts, 1 from a high-income country and another from a middle-income country, to (1) establish whether birth exposures may play a causal role in the development of childhood attention problems; and (2) identify whether confounding structures play a different role in parent-reported attention difficulties compared with attention deficit hyperactivity disorder (ADHD) diagnoses.Birth exposures included low birth weight (LBW), small-for-gestational age (SGA), small head circumference (HC) and preterm birth (PTB)). Outcomes of interest were attention difficulties  and ADHD . Associations between exposures and outcomes were compared between 7-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK (N=6849) and the 2004 Pelotas cohort in Brazil (N=3509).For attention difficulties (SDQ), the pattern of association with birth exposures was similar between cohorts: following adjustment, attention difficulties were associated with SGA  and small HC  in ALSPAC and SGA  in Pelotas. For ADHD, however, the pattern of association following adjustment differed markedly between cohorts. In ALSPAC, ADHD was associated with LBW  and PTB . In the Pelotas cohort, however, ADHD was associated with SGA .The findings suggest that fetal growth impairment may play a causal role in the development of attention difficulties in childhood, as similar associations were identified across both cohorts. Confounding structures, however, appear to play a greater role in determining whether a child meets the full diagnostic criteria for ADHD. The associations between fetal growth impairment or preterm birth (PTB) and childhood attention problems have been reported in a number of studies.7The current study aimed to help determine whether the association may be causal, by comparing two different cohorts, one from the UK, a high-income country ), and another from Brazil, a middle-income country (the 2004 Pelotas birth cohort study (Pelotas)). In addition to beginning 13 years apart, it is likely that different confounding structures exist within these populations.Determining the causality underlying any association is inherently difficult due to the limited ability to measure and control for all possible confounding variables.A secondary aim of this study is to determine whether the contribution of factors affecting these associations also vary as a function of symptom severity by comparing associations across two different attentional outcomes which vary both quantitatively (severity) and qualitatively  diagnostic criteria). Attention difficulties lie on a continuum from subclinical to clinical-level diagnoses, and brief behavioural questionnaires do not fully capture the entire scope of the clinical disorder.http://www.bris.ac.uk/alspac/researchers/data-access/data-dictionary/. Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and Local Research Ethics Committees.The ALSPAC cohort consisted of women with an expected delivery date between 1 April 1991 and 31 December 1992, in three health districts in the southwest of England.The 2004 Pelotas cohort consisted of children born in 2004, in the city of Pelotas, located in the Brazilian state of Rio Grande do Sul. Pelotas has approximately 340 000 inhabitants, and the major economic activities are agriculture (rice cultivation and cattle farming) and services, including two universities. Mothers residing in the urban area of Pelotas or in the adjacent neighbourhood of Jardim América were recruited and interviewed within 24 h of delivery.+0 weeks of gestation. SGA was identified using Williams’ curves for birth weight according to gestational age and gender.supplementary material.In both cohorts, neonatal weight and HC were measured within 24 h of delivery by trained researchers. Neonates were classified as low birth weight (LBW) if their birth weight fell under 2500 g,The hyperactivity/inattention subscale of the SDQ was used to assess child attention difficulties at a mean age of 6.79 years (SD=0.11) in ALSPAC and 6.70 years (SD=0.19) in Pelotas. The SDQ is a brief, parent-reported, behavioural screening questionnaire for children aged 3–16 years.24The DAWBA is a structured set of questions designed to generate DSM-IV psychiatric diagnoses for children aged 5–17 years.25supplementary material). Information on the procedure for obtaining data on all covariables is presented in online supplementary material.Data were collected on a range of maternal, demographic, gestational and perinatal variables in both the ALSPAC and Pelotas cohorts, listed in online supplementary table S1  unadjusted, (2) adjusted for maternal, family and demographic variables and (3) adjusted for gestational and perinatal variables. All models were adjusted for within-cohort variation in child age at the time of testing.All analyses were performed using IBM SPSS Statistics for Windows V.21.0.26supplementary table S2, online supplementary material). Attention difficulties, as reported on the SDQ, were higher in Pelotas compared with ALSPAC, as were the inattentive and combined subtypes of ADHD. There was no difference in the frequency of ‘any ADHD disorder’ and ‘hyperactive impulsive ADHD’ between cohorts .The prevalence of LBW, SGA, small HC and PTB was approximately twofold higher in Pelotas than in ALSPAC . The Pelotas cohort had a higher prevalence of mothers with a low level of education, a higher rate of low income, more mothers aged <19 years at delivery, a higher prevalence of smoking during pregnancy, a higher prevalence of depression during pregnancy, a higher rate of caesarean delivery and a higher prevalence of babies with a 5 min Apgar score <7. There were also differences in the associations between covariables and both birth exposures and attention problems, particularly in relation to caesarean sections . In ALSPAC, caesarean section was more strongly associated with each of the adverse birth outcomes compared with Pelotas. Furthermore, there was an opposite effect of caesarean sections on attention problems across cohorts, whereby caesarean section was associated with an increased risk of attention problems in ALSPAC, but a decreased risk in Pelotas . After controlling for covariables, the association between SGA and parent-reported attention difficulties at 7 years of age remained significant in both ALSPAC and Pelotas. No such pattern was identified for ADHD between cohorts, however, with associations in the opposite directions for all birth outcomes. As such, whereas being born SGA or with a small HC might play a causal role in the later development of attention difficulties, other factors may affect the more extreme cases of ADHD diagnosis.Our primary findings are consistent with previous studies that have identified SGAOur secondary findings showed that the pattern of association for ADHD differed significantly between cohorts while that of attention problems (SDQ) did not. These results indicate that confounding structures may have a greater effect on ADHD diagnoses than they do on milder attention difficulties. Even though milder attention difficulties and ADHD diagnoses both lie on the continuum of attention impairment, ADHD diagnoses represent a greater severity of impairment, compared with subclinical attention difficulties. Increased severity of impairment may arise from the accumulation of a greater number of risk factors, compared with subclinical attention difficulties, thus resulting in different aetiological profiles. The results of this study suggest that while impaired fetal growth may predispose a child to attention difficulties, whether their level of impairment reaches the threshold for ADHD diagnosis may be a function of environmental influences such as familial and childhood factors. This has been supported by a number of studies and reviews which have suggested that environmental influences in childhood, such as psychosocial adversity This study compared cohorts from a high-income and middle-income country as a method to examine causal inference in the associations between adverse birth outcomes and attention problems in childhood. Both cohorts were well established, used the same outcome measures at comparable time points in childhood, and have a range of sociodemographic, gestational and perinatal information, allowing for identical adjustment methods across both cohorts and minimising statistical heterogeneity. The advantage of comparing cohorts from high-income and middle-income countries is that there are expected to be systematic differences in confounding structures, which may impact the exposures and/or outcomes differently. For example, in this study, marked differences were identified between the ALSPAC and Pelotas cohorts with regard to the proportion and effects of caesarean delivery. In ALSPAC, caesarean delivery was associated with being born LBW, SGA or preterm; however there was no increased risk in Pelotas. In fact, caesarean delivery decreased the risk of being born with a small HC in Pelotas.These findings reflect marked differences between the UK and Brazil regarding elective caesarean sections. Whereas Brazil has one of the highest rates of caesarean section in the world,There are some limitations which must be acknowledged. First, although within-cohort variability in age at the time of testing was adjusted for in all models, children in the ALSPAC cohort were assessed on the DAWBA slightly older  than in the Pelotas cohort . It is unlikely, however, that this 11-month difference would cause a significant impact on the outcome, as ADHD symptoms have been shown to be relatively persistent across this time period.The findings of this study suggest some implications for the clinical management of children with disturbed fetal growth, for the guidance of education provisions for children with attention impairment, and for the direction of epidemiological and clinical research into factors associated with ADHD diagnosis. Effective interventions during early childhood for small HC/SGA children may promote early neurodevelopment, and reduce academic failure and behavioural difficulties at the onset of formal schooling.Associations between fetal growth impairment or preterm birth and attention problems in childhood have been well established, although it remains unclear whether these associations may be an artefact of residual confounding by social, health and economic factors. Cross-cohort comparison provides a method for improving causal inference in these associations by examining whether associations differ between cohorts with different confounding structures.This study identified that fetal growth impairment may play a causal role in the development of attention difficulties in childhood; however, social, health and economic factors may play a greater role in whether a child meets the full diagnostic criteria for attention deficit hyperactivity disorder (ADHD). Targeted early intervention programmes in early childhood may enhance attention development of children with fetal growth impairment, and buffer the effect of subclinical attention difficulties on educational outcomes.In conclusion, this study identified that fetal growth impairment may play a causal role in the development of attention difficulties in childhood, but that confounding structures may play a greater role in whether a child meets the full diagnostic criteria for ADHD. These findings have important implications for the clinical management of children with growth impairment during fetal life, where early intervention may buffer the effect of subclinical attention difficulties on educational outcomes.


The use of stimulant medication for Attention Deficit Hyperactivity Disorder (ADHD) to improve classroom behaviour and sustained concentration is well known. Achieving a better academic grade has been reported as the prime motivation for stimulant use and is an increasingly discussed topic. The proliferation of stimulant use for ADHD has been a cause for public, medical and policy concern in Australia. This paper explores individuals’ perceptions of ADHD, the meaning that the diagnosis carries for them and their attitudes to stimulant medication treatment.This qualitative study was underpinned by a social constructivist approach and involved semi-structured interviews with eight participants. The participants were parents of children with ADHD or were adults who themselves had been diagnosed with ADHD. Interviews were audiotaped, transcribed verbatim and thematically analysed.There were three interrelated yet contradictory overarching themes: (i) An impairment to achieving success, which can be a double-edged sword, but has to be fixed; (ii) Diagnosis as a relief that alleviates fault and acknowledges familial inheritance; (iii) Responsibility to be normal and to fit in with societal expectations. Collectively, these perceptions and meanings were powerful drivers of stimulant use.Paying attention to perceptions of ADHD and reasons for seeking or not seeking stimulant treatment is important when planning appropriate interventions for this condition.The online version of this article (doi:10.1186/s12913-016-1399-1) contains supplementary material, which is available to authorized users. Attention Deficit Hyperactivity Disorder (ADHD) is defined as a chronic neuro-developmental disorder characterised by the core symptoms of hyperactivity, impulsivity and inattention . It affePrescriptions for simulant medication have risen sharply in Western countries over the last decade –11. In AIn light of polarised debate, yet increasing use of stimulant treatment, individuals’ perceptions and experiences related to their child’s or their own diagnosis and treatment are important, but have largely been ignored. Taylor et al.  suggesteThis study used a qualitative approach to understand how parents of children diagnosed with ADHD, as well as adults diagnosed with ADHD perceived ADHD behaviour and stimulant treatment. The objectives of this study were to explore individuals’ perceptions of ADHD behaviour, the meaning that the diagnosis carries for them, and their attitudes to stimulant treatment derived from their everyday experiences.The qualitative approach used for this research was underpinned by a social constructivist philosophical stance, which emphasized the way individuals seek to understand their world and construct their own particular meanings that correspond to their experiences . It assuParticipants were recruited through volunteer sampling. An information sheet was distributed to primary schools, Department of Health Western Australia (WA) facilities, and the Learning and Attentional Disorder Society Support Groups in WA. A snowball technique in which participants were contacted via networks was also employed . ParticiHow was the decision made to seek for professional help?How did you feel being/your child being diagnosed with ADHD?Who do you think is responsible for this condition (ADHD)? WhyHow was the decision made to administer medication?How do you feel about administering medication for ADHD?How was your/child’s behaviour and your decision to administer medication received by your family and friends?How did their response make you feel? How did you want them to make you feel?In order to understand the individuals’ perceptions towards ADHD behaviour, after obtaining signed consent to participate, semi-structured face-to-face in-depth interviews were conducted to capture participant beliefs and thoughts in their own words . Seven kThe semi-structured interview kept the discussion on track within the available time restraints. Each interview lasted approximately one hour. This was long enough to encourage participants to talk freely, but not too long to tire them. To keep all interviews consistently focussed yet uninhibited, each participant was asked the same questions, but with a change in the order of questions as appropriate to maintain the flow of the interview. Additional open ended questions were used as prompts, depending on the nature of the discussion. With each participant’s permission all interviews were audio-recorded. The interviews took place at participants’ homes or at other alternative participant-nominated locations to allow them to retain some control over the interview situation and to render the interview session non-threatening, comfortable and convenient for them .Thematic analysis of participants’ transcribed interviews was conducted. Thematic analysis is a qualitative “method for identifying, analysing and reporting patterns (themes) within data”  (P. 79).An in-depth face-to-face interview method was used to explore individuals’ perceptions and beliefs towards ADHD and stimulant medication use in their own words. Therefore, the research method was anchored in the constructivist tradition to construct knowledge, meaning and understanding through human interactions, and so the trustworthiness was ensured in the course of conducting this study . Rigour The study adhered to ethical principles according to the National Health and Medical Research Council guidelines for conducting human research . EthicalThe analysis of the interviews revealed three overarching themes with two sub-themes for each. In sharing their experiences, participants touched on many common themes, yet sometimes these were in indirect contradiction to one another, demonstrating the complexity of the topic. Collectively, the interrelated yet contradictory perceptions and meanings were powerful drivers of stimulant use and are illustrated in Fig. I didn’t realise that the emotional problem that [my son] was experiencing was direct result of ADHD. I knew his hyperactivity was, but I didn’t know the emotional difficulties he had. I didn’t understand the impact of ADHD he had. I just saw the hyperactivity thing … struggling at school … but by the time he was 15, things were coming apart and really I did worry that he would suicide. (Jo)In discussing their experiences the participants expressed their negative and positive views towards ADHD. Parents reflecting on their experiences of their children suggested that children with ADHD were ‘difficult to manage’, ‘challenging’, ‘exhausting’, ‘not normal’ and had something ‘wrong’ in them. The parents stated that ADHD had a profound impact on their children’s learning at school, and noticed ‘lack of concentration’, ‘struggling with school work’, ‘not achieving at school’ and having ‘no friends’. Some noticed an emotional roller coaster in their children and one felt that her son was suicidal.As adults, participants described similar experiences including ‘lack of concentration’, ‘unable to remain seated’, difficulties in ‘waking up in the morning’, ‘organising tasks’, and ‘working with co-workers’.First it was a curse. It was so hard to control; it pulls them so difficult, they torn of their different feelings [sic]. But other side some of the things they do are amazing. It is like a gift, having extra especial power, but whether you can control them?Despite the difficulties they experienced, as parents, the participants often added positive attribution of their child’s ADHD for higher physical energy levels and cognitive abilities. Some believed that people with ADHD could be highly intelligent, and articulated that ADHD symptoms could be seen among famous people like ‘Aristotle’ and ‘Einstein’ throughout history. Annette had two of her children diagnosed with ADHD, and she thought:He was intellectually challenging and fun to rear … interesting … creative so far out of the box … you have to have eyes [in the] back of your head … never a dull moment … exhausting and emotionally scarring but incredibly interesting … intellectual stimulus … you can put [it] that way.Jo perceived a positive side of ADHD along with its negative connotation. She found her ADHD child was fun:They [her friends’ lives] are organized and dull – my one is chaotic and fun. We see more funny connection than other people see – more interesting … one of my friends said I was lot more fun before [treated].Jo was also diagnosed with ADHD and taking medications. She compared her life to her friends’ lives, and described:I think about this a lot and I’m not sure. We read a lot about those outstanding individuals for whom ADHD has been a blessing that they have made great discoveries and they are enormously successful …. There was a belief that human clan would not succeed without ADHD people in the society … [but] the flip side of me says, the success stories that … you do not hear about people who had their life in hell because of the emotional difficulties that ADHD creates. My son and I talked about this a lot. We both agreed [that]… the technicolour as we call the life we live is not worth, we prefer the black & white that everybody lives. So … it’s a double edged sword ….She then added when she was asked about her perception towards ADHD:We need to fix the problem. If he is not achieving at school what he is supposed to achieve and there is a problem, then do whatever it needs to be done to fix it ….Predominantly, however, ADHD was viewed as a ‘problem’ and a ‘disability’ that needs to be cured. Participants frequently mentioned the impact of ADHD behaviour on their child’s inability to ‘achieve’ at school and ‘function properly’ in society. They believed academic achievement is the key to success in life, and everybody should strive for success. Participants perceived ADHD as an ‘impairment’ to achieving ‘success’. As Susan stated:We think ADHD is impairment to success. We think success is everything. You got to be successful in life, academically and financially successful. You need to achieve regular goals, family/wife/kids. So, this is impairment, something to be cured … it has to be fixed.Kate’s perspective was similar:I was pleased to find out that there was something we could do because my son was really struggling. So it was very good for us to find out what the cause was of his problem … a big relief because he was clearly intelligent but he was clearly struggling.‘Diagnosis as a relief’ was the vernacular that all participants expressed knowing that the condition was a ‘neurobiological disorder’ caused by ‘missing chemicals in the brain’, and so was not their fault. The diagnosis relieved them from anxiety and stress, and provided reassurance that they or their children were not ‘bad’ or ‘naughty’, ‘lazy’ or ‘stupid’. The relief was also closely linked with the sense that there is help available, as Cheryl expressed:I actually felt relief. I was relieved because I realised that I was neither mad nor bad. There was certainly evidence that made other people to feel that I was bad … sometimes I thought am I crazy? People said I am rude, I am this and that, I am mad … but I thought I had a good heart … I am concerned about people’s wellbeing and I wanted to help…now I know why.Linda described her feelings after she was diagnosed with ADHD:… relaxed, thankful, happy, probably validated. Along the way we tried couple of others because he [son] had learning difficulties despite his intellect, we had him tested various other types of psychologically tested. They said he had learning difficulties associated with eye sight tracking which is very common with ADHD … but he had two other diagnoses that both said that I was an over protective mother that caused those hassles… so I was causing his problem. They said I was the problem, not him … it was all my fault and he had nothing wrong with it. So when he was diagnosed very comprehensively to fulfil more than minimum criteria [for ADHD], or maximum whatever you could have, it was a validation for him and for me. For him it was giving a name and understanding of why he was different.The diagnosis served parents as a mean of validating their parenting skills. They felt relief from a burden of guilt about being bad parents who could not discipline their children. As Jo felt:He is missing a chemical that doesn’t allow his brain to do what he needs to do. His brain is seeking stimulation or lacking the ability … it’s not an illness, but it’s a disability, because his body can’t do certain things.All participants had a biomedical understanding of ADHD and recognised it as a medical condition, but, did not perceive this condition as a mental illness. As Fiona (grandmother) described her grandson’s ADHD:Well, ADHD is a mental health issue in the DSM 4 and 5. According to that he has, but I don’t think about it to be honest … I don’t see him mentally … but if not treated it can be a mental health issue… [so] we accommodate for his [ADHD], so he won’t have any serious mental health [problem].Kate acknowledged that according to diagnostic criteria – the Diagnostic and Statistical Manual of Mental Disorder , ADHD isWhile the participants were reluctant to accept ADHD as a mental illness, they accepted this condition as a disability. It appeared that the disability status of ADHD might serve some purpose for two of the participants. Annette who had two of her children diagnosed with ADHD, found that school staff were supportive and they understood ADHD as a disability, and accommodated her children’s needs with special care as necessary. She, however, became “frustrated” with the social security personnel who did not think of ADHD as a disability and so did not think Annette should be eligible for a caregiver allowance for children with disabilities. However, Linda who did not perceive ADHD as a mental health problem, but believed it as a disability, was able to secure her disability pension for ADHD.My two older boys were diagnosed first, and listening to the paediatricians I realised that me and my wife had the same symptoms … so it came through our lines, therefore it was genetic and heritage ran from us … so we were treated.The relief was closely tied with perceiving ADHD as a genetic condition and realising that it ran in other family members. The participants mentioned that after one child was diagnosed, they started noticing similar symptoms in their other children and in other family members. Three of the participants were diagnosed after their children were diagnosed. Patrick was one of them:When I was pregnant, I did nothing wrong – no drinking, no drug, no bad food. I did everything by the book. I pumped myself from everything to be the best mother … since they were little I gave them boundaries, they were not allowed to have soft drinks, sugar … so, that was not the case … it [ADHD] was from the family … it’s genetic, it’s through the generation … through the father … while doing this [treatment for the first child] we sort of knew my husband had had it for a very long time. So we got him diagnosed … it’s hereditary … since my husband was diagnosed, my father-in-law with full of ADHD … in his 60s … said to me “I know I’ve got it”.Annette defended herself saying that she tried her best to be a ‘good mother’ during her pregnancy and afterwards doing ‘everything right’ and confirmed that ADHD was not her fault but a genetic disorder.Responsibility focused on parents’ abilities to solve the problem their child was experiencing at school and how stimulant medications helped the parents to fulfil their responsibilities. When describing the effect of medication, the parents and grandmother in the study placed emphasis on their child’s academic outcomes. The medication helped their child to ‘slow down’ and to engage ‘straight away’, which helped the child to ‘focus’, ‘concentrate better’ and ‘stay on task’ at school. The parents frequently mentioned that their child achieved higher grades after taking medications. Three parents said that the school teachers were also happy with the change in their child’s behaviour. For two parents, medications were believed to improve the ‘quality of life’ of the child. A few participants reported unpleasant effects of the stimulants, such as ‘mood swing’, ‘weight loss’, ‘decreased appetite’, ‘heart going faster’ and ‘trouble with sleeping’. They mentioned that their child was prescribed ‘Catapres’, which was usually prescribed for high blood pressure, to reduce the side-effect of the ADHD stimulants. All parents acknowledged stimulants as the most ‘evidence based’, ‘effective’ treatment. Four recognised the stimulant as an ‘important part’ of the ADHD treatment strategy, but as only ‘a part’, and said that their child also required psychotherapy, counselling, learning and behavioural management.… it’s not the decision that parents make easily. Any long term medication that you put your child on – this is something you have to think about long and hard. You have to decide that your child is diagnosed with something; you have to be satisfied with … pros and cons. … We tried occupational therapy … all sorts of things and wasted lots of money … but when it was clear that none of these were happening - it was already two years. Actually it was my biggest regret that I didn’t try with the medication at the beginning. He would have learnt a lot more at school in those two years.All parents reported in initial hesitation about using stimulant treatment, and expressed concern that the medication was ‘not good for health’. The grandmother mentioned that her initial resistance to medication was due to ongoing debate in the public sphere about over-diagnosis of and over-medication for ADHD. Two parents exhausted other alternative therapies before they agreed to stimulant medication. As Cheryl noted:I felt strange … but now it is a normal way of life and I don’t have a problem with it. So I don’t feel guilty about giving [medication] to them [the children]. As a parent, it is my responsibility to give them … it is no difference to my blood pressure tablet. I have to take blood pressure tablet or I would feel ill. … So, it’s [medication] a tool for them to cope. To me, it’s a tool to not feel inadequate, not feel different. I don’t want them to be in trouble. I don’t want them to feel that there was something wrong with them … it’s about self-esteem, confidence … about fitting in … learning, adaptation. … So they have their routine, and they have to take the medication every day to be normal.Parents felt it was their responsibility to boost their child’s ‘self-esteem’ to make them feel ‘normal’, so that they could ‘fit in’ society. Annette felt ‘strange’ with the idea of giving medication to manage behaviour initially; however, she convinced herself, thinking that giving stimulants to her children for ADHD was similar to taking blood pressure medication for herself. As such, she realised that she must not feel guilty about giving the ADHD medication, because it was her responsibility as a ‘good mother’ to help her children to improve their self-esteem and to allow them to fit into the community. As she articulated:proudly wear t-shirts writing on it – ‘ADHD makes me with a super power’, ‘I’ve forgotten my meds today’ so that [their] kids have a role model”. Annette also worked hard to educate other parents and children about ADHD so that other children would find her children ‘normal’ and ‘average’. As she described:So, I try to make it open as much as possible. I brought the book, and the teachers read with other kids that [her son’s name] has a brain, and he can’t concentrate. So the whole class would know – that’s how the teacher is educating the children. There is nothing wrong with [her son’s name], he has taken medication to calm down. So if the parents think that way, it should come from the children that [her son’s name] is not naughty, not a bad kid and he does not have any problem. I used to bring all books and DVD on ADHD and gave it to teachers to give it to other parents, because I wanted to have others to be educated.In many instances within the interviews the participants defended others’ perceptions of their ADHD behaviour or that of their children. They took a proactive approach to educate people about the nature of ADHD and the role of medication. They tried to move beyond what other people perceived about themselves and also any feeling of guilt that troubled them about giving medication to their child. They appeared to be justifying their decision to adhering medication treatment. They advocated for ADHD as a disability and the use of medication as an acceptable treatment choice. They believed that by educating others they would normalise ADHD, destigmatise stimulant treatment, and improve the outcomes of their and their child’s ADHD. Through this role, they constructed themselves and their child as normal. Patrick and Cheryl took on the position of educators for managing ADHD and stimulant treatment. Annette raised money for an ADHD charity. She and her husband, who was also diagnosed with ADHD, “I feel I am doing the right thing, but I wish I didn’t have to … I don’t like it [giving the medication], but I have to do it for his education. It’s a drug and it is not good for your body, … so on school holidays I don’t give it to him, he doesn’t need it for any reason, because he is what he is, so he can learn to be himself without the pill … but he has to go to school and do what he is told to do and to fit in. If he was diabetic, he had to have the medication. So I feel to be a responsible mum, he has to have it. I can’t have him the way he wants to be … that’s not responsible parenting … that’s wrong … giving him wrong expectations – so he has to take the pills … responsibility is you have to do what you have to do. If he is happy with his life later not to take it that would be his adult decision, [but] I will guide him until then.Susan also expressed her concern about giving medication to her child, but she justified her decision by saying that as a ‘responsible mum’ it was her duty to make her son fit into school and, therefore, she needed to continue with the medication. To minimise the harm of the medication and to allow her son to ‘learn to be himself’, she gave him a break from medication on school holidays.Susan, however, did not get her older son, who she thought also had ADHD, diagnosed and treated, because his condition was not affecting his education. She thought because he was ‘getting away with his school work’, she did not need to ‘medicate’ him. Through comparing ADHD medication to that taken for chronic diseases, such as diabetics or blood pressure, the parents emphasised the medication’s role in their child’s future – perceiving it as an investment for their child’s academic career, despite giving medication being an unpleasant feeling for them. Thus, they constructed themselves as a ‘good parent’ which allowed them to resolve any feelings of guilt about giving medication.I take my pill to cope with pressure … I could cope with the world … if I didn’t take the pill I wouldn’t be able to talk to you like this … wouldn’t be able to focus at work … my husband copes better with me when I am on the pill … so I have to [take medication], to stay in the relationship, to keep our life easy.For the adults with ADHD, taking medication was also about a responsibility to ‘fit in’ at work, within family and in relationships. They experienced improvement on every day activities, organising tasks at work, interpersonal skills and having meaningful conversations like ‘normal people’. They found their family and friends coped better with them when they were on medication. As such it was their responsibility to fit in with family and society. As Susan, who was also taking medication for ADHD, reflected:The findings of this exploratory study assist in understanding the complexity of ADHD. The results consisted of interrelated yet sometimes contradictory themes that depicted the participants’ views of ADHD and stimulant treatment. There were three overarching themes: an impairment to achieving success, diagnosis as a relief and responsibility. The findings from this study reflect the ontological and epistemological assumptions of the social constructivist framework , which aADHD is perceived to be an impairment to achieving success reflected in two sub-themes: ‘it’s a double-edged sword’ and ‘it has to be fixed’. The expression ‘double-edged sword’ in this study bares similarity to observations made in a UK study, where Singh et al.  noted thThe participants had a biomedical understanding of ADHD, ascribed to it a causal relationship with academic under performance  and acceParticipants in this study described a sense of relief following diagnosis, as it provided them with an explanation for the difficulties they or their child had experienced. The sense of relief stemmed from the fact that the diagnosis reassured them that the problem behaviour was not a personal failing in any moral sense, but rather a mental or at least cognitive disorder. In a phenomenological study of eight adults with ADHD in the UK, Young et al.  also repParental concern about the potential long-term side effects of stimulant medication was observed in another study in the US, where parents of children with ADHD expressed fears and accepted stimulant treatment reluctantly, even though they agreed that the medication helped their child . DespiteParental effort to improve their child’s academic performance and boost self-esteem is a rational consequence of the fact that higher education is a critical path to one’s career success in modern society , 53. To The adults diagnosed with ADHD in this study also referred to their needs to feel ‘normal’, to have the ability to interact with other people, to belong in the community and to be accepted by family and friends. These findings are consistent with other studies where adults with ADHD perceived that being accepted by others as a normal, responsible social being was important , 63, andThe findings from this study suggest that individuals’ perceptions and experiences shared much in common in the general sense, yet in detail the individuals’ journey had been diverse and complex. The findings underline that a person’s understanding of ADHD behaviour and their attitude towards stimulant treatment are important considerations in selecting an appropriate intervention and in developing policy on the regulation of stimulant treatment use. Individuals who do not experience the perceptions of difficulties in academic performance or fitting in with society may not necessarily seek stimulant treatment, even if it would be beneficial from an objective viewpoint. This was noted in the interview with Susan, who thought that her older son also had ADHD, but did not seek treatment for him because he was achieving school grades to her satisfaction. On the other hand, desire to accelerate academic performance may motivate individuals to pursue the non-medical use of stimulants , 66. ParThis study contributes to the body of literature with its focus on individuals’ perceptions of ADHD and attitudes towards stimulant medication, including perceived roles of medication in child’s future. Paying attention to perceptions of ADHD and reasons for seeking or not seeking stimulant treatment is important when planning appropriate interventions for this condition to avoid over-diagnosis and overtreatment. The findings reinforce the need for more education of medical professionals to enable them to plan appropriate interventions and to give appropriate support and guidance to optimise outcomes for individuals with ADHD and their families.There are some limitations to this study that deserve consideration. Firstly, the participants were white, middle class people, living in a metropolitan area. As such, their perceptions may not reflect those of community members from other backgrounds, highlighting the need for research among culturally, ethnically and socioeconomically diverse groups in the future. Secondly, as the sample was largely female, the views of a wider range of males were somewhat absent from the research. Thirdly, three of the four adults with ADHD were parents who were diagnosed after their children had been diagnosed, and mostly described their experience as being parents. Even though the experience of one adult with no children was little different from the parents diagnosed with ADHD, findings drawn from this sample may not be transferrable to the perceptions of ADHD and stimulant treatment of adults diagnosed with ADHD. Fourthly, given the nature of qualitative analysis, this study represents only one interpretation of the participants’ experiences, hence it delivers a partial, static picture of their perceptions of ADHD behaviour and attitudes towards stimulant treatment. Further, the analysis primarily denotes interpretations made by a single research group with the possibility that others might draw different inferences. Despite its limitations, this study does provide some important data with respect to the factors that shape individuals’ attitudes towards ADHD and influence individuals’ treatment choices. Building on these insights, further research can be conducted in a format that would canvas a wider range of views. Future research could also include a multi-perspective and longitudinal design, interviewing children, young adults and their parents to explore evolving perceptions of ADHD and medication over time.The participants in this study perceived ADHD behaviour as an impairment to achieving success in life. A desire for academic achievement, good self-esteem, being normal and a sense of belongingness were important driving forces for stimulant treatment use among parents of children diagnosed with ADHD. Adults diagnosed with ADHD found stimulant medication was important for a responsible person to fit in to the community. The findings have potential to be used to raise awareness and understanding among medical practitioners working with ADHD adults, children and their parents of the perceived reasons why individuals seek or do not seek stimulant treatment.In accordance with the Human Research Ethics Committee, University of Western Australia (HREC-UWA) protocol, research data involving human participants cannot be made available to the public for confidentiality and ethical reasons. Demographic and interview questions are included as an additional file.