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Background\ud Attention deficit hyperactivity disorder (ADHD) is highly heritable, but little is known about the relative effects of transmitted (i.e. direct) and non-transmitted (i.e. indirect) common variant risks. Using parent-offspring trios, we tested whether polygenic liability for neurodevelopmental and psychiatric disorders and lower cognitive ability is over-transmitted to ADHD probands. We also tested for indirect or ‘genetic nurture’ effects, by examining whether non-transmitted ADHD polygenic liability is elevated. Finally, we examined whether complete trios are representative of the clinical ADHD population.\ud \ud Methods\ud Polygenic risk scores (PRS) for ADHD, anxiety, autism, bipolar disorder, depression, obsessive-compulsive disorder (OCD), schizophrenia, Tourette’s syndrome, and cognitive ability were calculated in UK controls (N=5,081), UK probands with ADHD (N=857), their biological parents (N=328 trios), and also a replication sample of 844 ADHD trios.\ud \ud Results\ud ADHD PRS were over-transmitted and cognitive ability and OCD PRS were under-transmitted. These results were independently replicated. Over-transmission of polygenic liability was not observed for other disorders. Non-transmitted alleles were not enriched for ADHD liability compared to controls. Probands from incomplete trios had more hyperactive-impulsive and conduct disorder symptoms, lower IQ, and lower socioeconomic status than complete trios. PRS did not vary by trio status.\ud \ud Conclusions\ud The results support direct transmission of polygenic liability for ADHD and cognitive ability from parents to offspring, but not for other neurodevelopmental/psychiatric disorders. They also suggest that non-transmitted neurodevelopmental/psychiatric parental alleles do not contribute indirectly to ADHD via genetic nurture. Furthermore, ascertainment of complete ADHD trios may be non-random, in terms of demographic and clinical factors.

Objective: We investigated whether “late-onset” ADHD that emerges in adolescence/adulthood is similar in risk factor profile to: (1) child-onset ADHD, but emerges later because of scaffolding/compensation from childhood resources; and (2) depression, because it typically onsets in adolescence/adulthood and shows symptom and genetic overlaps with ADHD. Methods: We examined associations between late-onset ADHD and ADHD risk factors, cognitive tasks, childhood resources and depression risk factors in a population-based cohort followed-up to age 25 years ( N=4224–9764). Results: Parent-rated late-onset ADHD was like child-onset persistent ADHD in associations with ADHD polygenic risk scores and cognitive task performance, although self-rated late-onset ADHD was not. Late-onset ADHD was associated with higher levels of childhood resources than child-onset ADHD and did not show strong evidence of association with depression risk factors. Conclusions: Late-onset ADHD shares characteristics with child-onset ADHD when parent-rated, but differences for self-reports require investigation. Childhood resources may delay the onset of ADHD.

It is unknown why attention deficit hyperactivity disorder (ADHD) is more common in males, whereas anxiety and depression show a female population excess. We tested the hypothesis that anxiety and depression risk alleles manifest as ADHD in males. We also tested whether anxiety and depression in children with ADHD show a different etiology to typical anxiety and depression and whether this differs by sex. The primary clinical ADHD sample consisted of 885 (14% female) children. Psychiatric symptoms were assessed using standardized interviews. Polygenic risk scores (PRS) were derived using large genetic studies. Replication samples included independent clinical ADHD samples (N = 3,794; 25.7% female) and broadly defined population ADHD samples (N = 995; 33.4% female). We did not identify sex differences in anxiety or depression PRS in children with ADHD. In the primary sample, anxiety PRS were associated with social and generalized anxiety in males, with evidence of a sex-by-PRS interaction for social anxiety. These results did not replicate in the broadly defined ADHD sample. Depression PRS were not associated with comorbid depression symptoms. The results suggest that anxiety and depression genetic risks are not more likely to lead to ADHD in males. Also, the evidence for shared etiology between anxiety symptoms in those with ADHD and typical anxiety was weak and needs replication.

Background\ud There is increasing interest in digital technologies to help improve children and young people’s mental health, and the evidence for the effectiveness for these approaches is rising. However, there is concern regarding levels of user engagement, uptake and adherence. Key guidance regarding digital health interventions stress the importance of early user input in the development, evaluation and implementation of technologies to help ensure they are engaging, feasible, acceptable and potentially effective. Co‐design is a process of active involvement of stakeholders, requiring a change from the traditional approaches to intervention development. However, there is a lack of literature to inform the co‐design of digital technologies to help child and adolescent mental health.\ud \ud Methods\ud We reviewed the literature and practice in the co‐design of digital mental health technologies with children and young people. We searched Medline, PsycInfo and Web of Science databases, guidelines, reviews and reference lists, contacted key authors for relevant studies, and extracted key themes on aspects of co‐design relevant to practice. We supplemented this with case studies and methods reported by researchers working in the field.\ud \ud Results\ud We identified 25 original articles and 30 digital mental health technologies that were designed/developed with children and young people. The themes identified were as follows: principles of co‐design (including potential stakeholders and stages of involvement), methods of involving and engaging the range of users, co‐designing the prototype and the challenges of co‐design.\ud \ud Conclusions\ud Co‐design involves all relevant stakeholders throughout the life and research cycle of the programme. This review helps to inform practitioners and researchers interested in the development of digital health technologies for children and young people. Future work in this field will need to consider the changing face of technology, methods of engaging with the diversity in the user group, and the evaluation of the co‐design process and its impact on the technology.

BackgroundAttention deficit hyperactivity disorder (ADHD) is highly heritable, but little is known about the relative effects of transmitted (i.e. direct) and non-transmitted (i.e. indirect) common variant risks. Using parent-offspring trios, we tested whether polygenic liability for neurodevelopmental and psychiatric disorders and lower cognitive ability is over-transmitted to ADHD probands. We also tested for indirect or ‘genetic nurture’ effects, by examining whether non-transmitted ADHD polygenic liability is elevated. Finally, we examined whether complete trios are representative.MethodsPolygenic risk scores (PRS) for ADHD, anxiety, autism, bipolar disorder, depression, obsessive-compulsive disorder (OCD), schizophrenia, Tourette’s syndrome, and cognitive ability were calculated in UK controls (N=5,081), UK probands with ADHD (N=857), and, where available, their biological parents (N=328 trios), and also a replication sample of 844 ADHD trios.ResultsADHD PRS were over-transmitted and cognitive ability and OCD PRS were under-transmitted to probands. These results were independently replicated. Over-transmission of polygenic liability was not observed for other disorders. Non-transmitted alleles were not enriched for ADHD liability compared to controls. Probands from incomplete trios had more hyperactive-impulsive and conduct disorder symptoms, lower IQ, and lower socioeconomic status than complete trios. PRS did not vary by trio status.ConclusionsThe results support direct transmission of polygenic liability for ADHD and cognitive ability from parents to offspring, but not for other neurodevelopmental/psychiatric disorders. They also suggest that non-transmitted neurodevelopmental/psychiatric parental alleles do not contribute indirectly to ADHD via genetic nurture. Furthermore, ascertainment of complete ADHD trios may be non-random, in terms of demographic and clinical factors.

Background Irritability is especially pertinent to those with Attention Deficit Hyperactivity Disorder (ADHD) as it is highly prevalent and associated with a more severe clinical presentation and poorer longitudinal outcomes. Preliminary evidence suggests that top-down cognitive processes taking place in emotional contexts (i.e., hot executive functions) as opposed to those evoked in abstract scenarios (i.e., cool executive functions) may be relevant to the presentation of irritability in ADHD. This study explored the cognitive mechanisms underlying irritability in young people with ADHD, hypothesising that irritability would be associated with hot, but not cool, executive function impairments. Methods Our sample included 219 individuals with ADHD. A composite irritability score was derived extracting items from a parent interview, with scores ranging from 0 to 5. Associations were investigated using linear regression analyses, between irritability and four hot tasks measuring sensitivity to risk, risk-taking behaviour following reward or punishment, acceptance of reward delay and reaction to unfair behaviour from others, and two cool tasks measuring set-shifting and motor inhibition. Results As hypothesised, there were no significant associations between irritability and cool executive functions in those with ADHD; however, contrary to expectations, there was also no significant evidence that hot executive functions were associated with irritability. Conclusions These results, in a large well characterised sample and using a comprehensive task battery, suggest that the variation in irritability in those with ADHD may not be associated with differences in hot or cool executive function performance.

SUMMARY Depression and anxiety are common in adolescents, but most affected will not get any formal help. Digital mental health technologies (i.e. resources and interventions to support and improve mental health) are a potential way to extend the reach and increase adolescents’ access to therapies, at a relatively low cost. Many young people can access the internet and mobile technologies, including in low- and middle-income countries. There has been increased interest in integrating technologies in a range of settings, especially because of the effect of the COVID-19 pandemic on adolescent mental health, at a time when services are under pressure. This clinical review gives an overview of digital technologies to support the prevention and management of depression and anxiety in adolescence. The technologies are presented in relation to their technological approaches, underlying psychological or other theories, setting, development, evaluations to date and how they might be accessed. There is also a discussion of the potential benefits, challenges and future developments in this field.

SummaryTo investigate the accuracy of the age-at-onset criterion in those who meet other DSM-5 criteria for attention-deficit hyperactivity disorder, using a prospective population cohort we compared four different approaches to asking those aged 25 years (n = 138) when their symptoms started. Receiver operating characteristic curves showed variation between the approaches (χ(3) = 8.99, P = 0.03); all four showed low discrimination against symptoms that had been assessed when they were children (area under the curve: 0.57–0.68). Asking adults to recall specific symptoms may be preferable to recalling at what age symptoms started. However, limitations to retrospective recall add to debate on the validity of ADHD age-at-onset assessment.

Highlights • In a sample of recurrently depressed women, 12.8% had elevated ADHD symptoms. • 3.4% met ADHD diagnostic criteria; none had a diagnosis from a medical professional. • ADHD was associated with earlier-onset, more impairing and recurrent depression. • Recurrently depressed women with ADHD symptoms were more likely to be hospitalised. • ADHD symptoms were associated with taking non-first-line antidepressant medication., Background Depression is highly heterogeneous in its clinical presentation. Those with attention deficit/hyperactivity disorder (ADHD) may be at risk of a more chronic and impairing depression compared to those with depression alone according to studies of young people. However, no studies to date have examined ADHD in recurrently depressed adults in mid-life. Method In a sample of women in mid-life (n=148) taken from a UK based prospective cohort of adults with a history of recurrent depression, we investigated the prevalence of ADHD and the association of ADHD with clinical features of depression. Results 12.8% of the recurrently depressed women had elevated ADHD symptoms and 3.4% met DSM-5 diagnostic criteria for ADHD. None of the women reported having a diagnosis of ADHD from a medical professional. ADHD symptoms were associated with earlier age of depression onset, higher depression associated impairment, a greater recurrence of depressive episodes and increased persistence of subthreshold depression symptoms over the study period, higher levels of irritability and increased risk of self-harm or suicide attempt. ADHD symptoms were associated with increased risk of hospitalisation and receiving non-first-line antidepressant medication. Limitations ADHD was measured using a questionnaire measure. We focussed on mothers in a longitudinal study of recurrent depression, so the findings may not apply to males or other groups. Conclusions Higher ADHD symptoms appear to index a worse clinical presentation for depression. Clinical implications include that in women with early onset, impairing and recurrent depression, the possibility of underlying ADHD masked by depression needs to be considered.

Attention Deficit Hyperactivity Disorder (ADHD) symptoms typically onset early and persist into adulthood for many. Robust investigation of symptom continuity and discontinuity requires repeated assessments using the same measure, but research is lacking into whether measures used to assess ADHD symptoms in childhood are also valid in adulthood. The Strengths and Difficulties Questionnaire (SDQ) is widely used to assess ADHD symptoms in children, but little is known about its utility in adulthood. The aim of this study was to assess the validity of the SDQ hyperactivity/ADHD subscale to distinguish between cases and non-cases of DSM-5 ADHD at age 25 years in a UK population cohort (N = 4121). ADHD diagnosis was derived using the Barkley Adult ADHD Rating Scale-IV. Analyses suggested that the self-rated SDQ ADHD subscale had high validity in distinguishing ADHD cases/non-cases in young adulthood (area under the curve=0.90, 95% CI=0.87–0.93) and indicated a lower cut-point for identifying those who may have an ADHD diagnosis in this age group compared to that currently recommended for younger ages. Findings were similar for parent-reports. Our findings suggest that the SDQ is suitable for ADHD research across different developmental periods, which will aid the robust investigation of ADHD from childhood to young adulthood.

BackgroundDepression is highly heterogeneous in its clinical presentation. Those with attention deficit/hyperactivity disorder (ADHD) may be at risk of a more chronic and impairing depression compared to those with depression alone according to studies of young people. However, no studies to date have examined ADHD in recurrently depressed adults in mid-life.AimsTo investigate ADHD in women in mid-life with a history of recurrent depression.MethodIn a sample of women in mid-life (n=148) taken from a UK based prospective cohort of adults with a history of recurrent depression, we investigated the prevalence of ADHD and the association of ADHD with clinical features of depression.Results12.8% of the recurrently depressed women had elevated ADHD symptoms and 3.4% met DSM-5 diagnostic criteria for ADHD. None of the women reported having a diagnosis of ADHD from a medical professional. ADHD was associated with earlier age of depression onset, higher depression associated impairment, a greater recurrence of depressive episodes and increased persistence of subthreshold depression symptoms over the study period, higher levels of irritability and increased risk of self-harm or suicide attempt. ADHD symptoms were associated with increased risk of hospitalisation and receiving non-first line antidepressant medication.ConclusionsHigher ADHD symptoms appear to index a worse clinical presentation for depression. Findings suggest that in women with early onset, impairing and recurrent depression, the possibility of underlying ADHD masked by depression needs to be considered.

Attention Deficit Hyperactivity Disorder (ADHD) symptoms typically onset early in development and persist into adulthood for many. Robust investigation of symptom continuity and discontinuity requires repeated assessments using the same measure, but research is lacking into whether measures used to assess ADHD symptoms in childhood are also valid in adulthood. The Strengths and Difficulties Questionnaire (SDQ) has been widely used to measure ADHD symptoms in children, but little is known about its utility to measure ADHD in adulthood. We used Receiver Operating Characteristic (ROC) curve analyses to examine the validity of the SDQ hyperactivity/ADHD subscale to distinguish between cases and non-cases of DSM-5 ADHD classified using the Barkley Adult ADHD Rating Scale-IV (BAARS-IV) at age 25 years in a UK population cohort (N=4121). Analyses suggested that the SDQ ADHD subscale had high accuracy in distinguishing ADHD cases from non-cases in young adulthood (area under the curve=0.90, 95% CI=0.87-0.93) and indicated a lower cut-point for identifying those who may have an ADHD diagnosis in this age group compared to that currently recommended for younger ages.Our findings suggest that the SDQ is suitable for ADHD research across different developmental periods, which will aid the robust investigation of ADHD from childhood to young adulthood.HighlightsThe SDQ is widely used to measure ADHD symptoms in childrenWe investigated the validity of the SDQ to assess ADHD at age 25 yearsThe SDQ ADHD subscale had high accuracy in distinguishing DSM-5 ADHD cases from non-casesA lower cut-point is needed to identify ADHD diagnosis in young adulthood compared to younger agesThe SDQ is appropriate for ADHD research across different development periods

Background Treatment and prevention guidelines highlight the key role of health information and evidence-based psychosocial interventions for adolescent depression. Digital health technologies and psychoeducational interventions have been recommended to help engage young people and to provide accurate health information, enhance self-management skills, and promote social support. However, few digital psychoeducational interventions for adolescent depression have been robustly developed and evaluated in line with research guidance. Objective We aimed to evaluate the feasibility, acceptability, and potential impact of a theory-informed, co-designed digital intervention program, MoodHwb. Methods We used a mixed methods (quantitative and qualitative) approach to evaluate the program and the assessment process. Adolescents with or at elevated risk of depression and their parents and carers were recruited from mental health services, school counselors and nurses, and participants from a previous study. They completed a range of questionnaires before and after the program (related to the feasibility and acceptability of the program and evaluation process, and changes in mood, knowledge, attitudes, and behavior), and their Web usage was monitored. A subsample was also interviewed. A focus group was conducted with professionals from health, education, social, and youth services and charities. Interview and focus group transcripts were analyzed using thematic analysis with NVivo 10 (QSR International Pty Ltd). Results A total of 44 young people and 31 parents or carers were recruited, of which 36 (82%) young people and 21 (68%) parents or carers completed follow-up questionnaires. In all, 19 young people and 12 parents or carers were interviewed. Overall, 13 professionals from a range of disciplines participated in the focus group. The key themes from the interviews and groups related to the design features, sections and content, and integration and context of the program in the young person’s life. Overall, the participants found the intervention engaging, clear, user-friendly, and comprehensive, and stated that it could be integrated into existing services. Young people found the “Self help” section and “Mood monitor” particularly helpful. The findings provided initial support for the intervention program theory, for example, depression literacy improved after using the intervention (difference in mean literacy score: 1.7, 95% CI 0.8 to 2.6; P Conclusions Findings from this early stage evaluation suggest that MoodHwb and the assessment process were feasible and acceptable, and that the intervention has the potential to be helpful for young people, families and carers as an early intervention program in health, education, social, and youth services and charities. A randomized controlled trial is needed to further evaluate the digital program.

BackgroundRecent case-control genetic studies of attention deficit hyperactivity disorder (ADHD) have implicated common and rare genetic risk alleles, highlighting the polygenic and complex aetiology of this neurodevelopmental disorder. Studies of other neurodevelopmental disorders, such as autism spectrum disorder (ASD), Tourette disorder, developmental delay/intellectual disability, and schizophrenia indicate that identification of specific risk alleles and additional insights into disorder biology can be gained by studying non-inherited de novo variation. In this study, we aimed to identify large de novo copy number variants (CNVs) in children with ADHD.MethodsChildren with a confirmed diagnosis of ADHD and their parents were genotyped and included in this sample. We used PennCNV to call large (>200kb) CNVs and identified those calls that were present in the proband and absent in both biological parents.ResultsIn 305 parent-offspring trios, we detected 14 de novo CNVs in 13 probands, giving a mutation rate of 4.6% and a per individual rate of 4.3%. This rate is higher than published reports in controls and similar to those observed for ASD, schizophrenia and Tourette disorder. We also identified de novo mutations at 4 genomic loci (15q13.1-13.2 duplication, 16p13.11 duplication, 16p12.2 deletion and 22q11.21 duplication) that have previously been implicated in other neurodevelopmental disorders, two of which (16p13.11 and 22q11.21) have also been implicated in case-control ADHD studies.ConclusionsOur study complements ADHD case-control genomic analyses and demonstrates the need for larger parent-offspring trio genetic studies to gain further insights into the complex aetiology of ADHD.

BACKGROUND Treatment and prevention guidelines highlight the key role of health information and evidence-based psychosocial interventions for adolescent depression. Digital health technologies and psychoeducational interventions have been recommended to help engage young people and to provide accurate health information, enhance self-management skills, and promote social support. However, few digital psychoeducational interventions for adolescent depression have been robustly developed and evaluated in line with research guidance. OBJECTIVE We aimed to evaluate the feasibility, acceptability, and potential impact of a theory-informed, co-designed digital intervention program, MoodHwb. METHODS We used a mixed methods (quantitative and qualitative) approach to evaluate the program and the assessment process. Adolescents with or at elevated risk of depression and their parents and carers were recruited from mental health services, school counselors and nurses, and participants from a previous study. They completed a range of questionnaires before and after the program (related to the feasibility and acceptability of the program and evaluation process, and changes in mood, knowledge, attitudes, and behavior), and their Web usage was monitored. A subsample was also interviewed. A focus group was conducted with professionals from health, education, social, and youth services and charities. Interview and focus group transcripts were analyzed using thematic analysis with NVivo 10 (QSR International Pty Ltd). RESULTS A total of 44 young people and 31 parents or carers were recruited, of which 36 (82%) young people and 21 (68%) parents or carers completed follow-up questionnaires. In all, 19 young people and 12 parents or carers were interviewed. Overall, 13 professionals from a range of disciplines participated in the focus group. The key themes from the interviews and groups related to the design features, sections and content, and integration and context of the program in the young person’s life. Overall, the participants found the intervention engaging, clear, user-friendly, and comprehensive, and stated that it could be integrated into existing services. Young people found the “Self help” section and “Mood monitor” particularly helpful. The findings provided initial support for the intervention program theory, for example, depression literacy improved after using the intervention (difference in mean literacy score: 1.7, 95% CI 0.8 to 2.6; PP=.006 for parents and carers). CONCLUSIONS Findings from this early stage evaluation suggest that MoodHwb and the assessment process were feasible and acceptable, and that the intervention has the potential to be helpful for young people, families and carers as an early intervention program in health, education, social, and youth services and charities. A randomized controlled trial is needed to further evaluate the digital program.

Objective: The objective of this study was to examine the association between parent mental health (ADHD and depression) and offspring performance on neurocognitive tasks in children with ADHD. Method: The clinical sample consisted of 570 children (85% males, mean age: 10.77 years) with ADHD who completed neurocognitive tasks measuring working memory, attention set-shifting, and motivational deficits. Questionnaire measures were used to assess ADHD and depression symptom presence in parents. Results: Controlling for ADHD severity, children of parents with ADHD had poorer working memory (B = −0.25, 95% confidence interval [CI] [−0.45, −0.07], p = .01) and increased errors on the extra dimensional shift stage of the set-shifting task (B = 0.26 95% CI [0.02, 0.50], p = .04). Parent depression was not associated with offspring performance on any of the assessed neurocognitive tasks. Conclusion: Children with ADHD who have a parent with ADHD symptom presence are a subgroup of children who may have additional neurocognitive impairments that have potential implications when implementing interventions that target cognition and learning.

Previous cross-sectional research has shown that parents of children with attention deficit hyperactivity disorder (ADHD) have high rates of psychopathology, especially ADHD and depression. However, it is not clear whether different types of parent psychopathology contribute to the course and persistence of ADHD in the child over time. The aim of this two wave study was to investigate if mother self-reported ADHD and depression influence persistence of offspring ADHD and conduct disorder symptom severity in adolescents diagnosed with ADHD in childhood. A sample of 143 males with a confirmed diagnosis of ADHD participated in this study. ADHD and conduct disorder symptoms were assessed at baseline and reassessed 4 years later. The boys in this sample had a mean age of 10.7 years at Time 1 (SD 2.14, range 6–15 years) and 13.73 years at Time 2 (SD 1.74, range 10–17 years). Questionnaire measures were used to assess ADHD and depression symptoms in mothers at Time 1. Mother self-reported ADHD was not associated with a change in child ADHD or conduct symptom severity over time. Mother self-reported depression was found to predict an increase in child conduct disorder symptoms, but did not contribute to ADHD symptom levels. This study provides the first evidence that concurrent depression in mothers may be a predictor of worsening conduct disorder symptoms in adolescents with ADHD. It may, therefore, be important to screen for depression in mothers of children with ADHD in clinical practice to tailor interventions accordingly.

Although Attention Deficit Hyperactivity Disorder (ADHD) is recognised to be a familial and heritable disorder, little is known about the broader family characteristics of having a parent with ADHD problems. The main aim of this study was to investigate the relationship between parent ADHD problems, child clinical presentation and family functioning in a sample of children with ADHD. The sample consisted of 570 children with ADHD. Child psychopathology was assessed using a semi-structured diagnostic interview. Questionnaires were used to assess ADHD in the parents (childhood and current symptoms), family environment and mother/father-child relationship. Parental ADHD problems were associated with a range of adverse clinical outcomes in children with no difference in effects for mothers with ADHD problems compared to fathers with ADHD problems. Levels of maternal hostility were higher in families where mothers had ADHD problems, but reduced where fathers had ADHD problems. Parental ADHD problems index higher risk for more severe clinical presentation of ADHD in children and higher levels of family conflict (where there are maternal but not paternal ADHD problems). This study highlights that children with more severe behavioural symptoms are more likely to have a parent with persistent ADHD which has important implications when considering treatment and intervention strategies. Electronic supplementary material The online version of this article (doi:10.1007/s00787-013-0378-x) contains supplementary material, which is available to authorized users.

OBJECTIVE Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. METHOD Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. RESULTS Polygenic risk for ADHD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by the aggression items. CONCLUSIONS Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity. OBJECTIVE Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. METHOD Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. RESULTS Polygenic risk for ADHD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by the aggression items. CONCLUSIONS Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity.

BackgroundSome research suggests that children with attention-deficit hyperactivity disorder (ADHD) have a higher than expected risk of bipolar affective disorder. No study has examined the prevalence of bipolar disorder in a UK sample of children with ADHD.AimsTo examine the prevalence of bipolar disorder in children diagnosed with ADHD or hyperkinetic disorder.MethodPsychopathology symptoms and diagnoses of bipolar disorder were assessed in 200 young people with ADHD (170 male, 30 female; age 6–18 years, mean 11.15, s.d. = 2.95). Rates of current bipolar disorder symptoms and diagnoses are reported. A family history of bipolar disorder in parents and siblings was also recorded.ResultsOnly one child, a 9-year-old boy, met diagnostic criteria for both ICD–10 hypomania and DSM–IV bipolar disorder not otherwise specified.ConclusionsIn a UK sample of children with ADHD a current diagnosis of bipolar disorder was uncommon.

BackgroundSubmicroscopic, rare chromosomal copy number variants (CNVs) contribute to neurodevelopmental disorders but it is not known whether they define atypical clinical cases.AimsTo identify whether large, rare CNVs in attention-deficit hyperactivity disorder (ADHD) are confined to a distinct clinical subgroup.MethodA total of 567 children with ADHD aged 5–17 years were recruited from community clinics. Psychopathology was assessed using the Child and Adolescent Psychiatric Assessment. Large, rare CNVs (>500 kb, ResultsCopy number variant carriers (13.6%) showed no differences from non-carriers in ADHD symptom severity, symptom type, comorbidity, developmental features, family history or pre-/ perinatal markers. The only significant difference was a higher rate of intellectual disability (24% v. 9%, χ2 = 15.5, P = 0.001). Most CNV carriers did not have intellectual disability.ConclusionsLarge, rare CNVs are not restricted to an atypical form of ADHD but may be more highly enriched in children with cognitive problems.