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Contains fulltext : 290804.pdf (Publisher’s version ) (Closed access) Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention. 01 februari 2023

Objective: Though psychiatric illnesses have been associated with increased COVID-19 infection risk, limited information exists about the relationship between ADHD and COVID-19. Methods: Using the TriNetX COVID-19 Research Network, we examined the impact of ADHD diagnosis and treatment on COVID-19 infection rates and outcomes. Results: ADHD patients had greater risk of COVID-19 (risk ratio (RR) 1.11, 95% CI [1.09, 1.12]). Increased risk was higher in females than males, and highest among Asian and Black patients. Within 60 days after COVID-19 diagnosis, ADHD patients had lower rates of hospitalization (RR 0.91, 95% CI [0.86, 0.96]) and mechanical ventilation (RR 0.69, 95% CI [0.58, 0.83]), and a nonsignificant reduced death rate (RR 0.65, 95% CI [0.42, 1.02]). Patients who recently received ADHD medication had higher rates of COVID-19 (RR 1.13; 95% CI [1.10, 1.15]). Conclusion: ADHD poses increased risk for COVID-19, but may reduce risk of severe outcomes. ADHD medications modestly impacted COVID-19 risk.

PURPOSE: To assess the utility of the Child Behavior Checklist (CBCL) to identify meaningful subtypes of emotional dysregulation in an outpatient pediatric psychiatry clinic. METHODS: The sample consisted of 417 newly referred youth 6–18 years of age. Parents completed the CBCL and rating scales measuring executive function deficits, social functioning, and quality of life. Patients were stratified into subtypes of emotional dysregulation and compared on clinical correlates based on the A-A-A profile consisting of the CBCL Anxious/Depressed, Aggressive Behavior, and Attention Problems (A-A-A) scales. RESULTS: 67% of youth had emotional dysregulation (CBCL A-A-A T-score ≥180) and of these, 39% had a positive CBCL-Bipolar (BP) profile (A-A-A T-score ≥210), 24% had depression without the BP profile (CBCL Anxious/Depressed and/or Withdrawn/Depressed T-scores ≥70 and A-A-A T-score ≥180 and

In vivo experimental analysis of human brain tissue poses substantial challenges and ethical concerns. To address this problem, we developed a computational method called the Brain Gene Expression and Network-Imputation Engine (BrainGENIE) that leverages peripheral-blood transcriptomes to predict brain tissue-specific gene-expression levels. Paired blood-brain transcriptomic data collected by the Genotype-Tissue Expression (GTEx) Project was used to train BrainGENIE models to predict gene-expression levels in ten distinct brain regions using whole-blood gene-expression profiles. The performance of BrainGENIE was compared to PrediXcan, a popular method for imputing gene expression levels from genotypes. BrainGENIE significantly predicted brain tissue-specific expression levels for 2947-11,816 genes (false-discovery rate-adjusted p

Supplemental material, sj-docx-1-jad-10.1177_10870547231155875 for Progress and Pitfalls in the Provision of Quality Care for Adults With Attention Deficit Hyperactivity Disorder in Primary Care by Elisabeth F. Callen, Tarin L. Clay, Jillian Alai, David W. Goodman, Lenard A. Adler, Joel Shields and Stephen V. Faraone in Journal of Attention Disorders

Supplemental material, sj-docx-1-jad-10.1177_10870547231155875 for Progress and Pitfalls in the Provision of Quality Care for Adults With Attention Deficit Hyperactivity Disorder in Primary Care by Elisabeth F. Callen, Tarin L. Clay, Jillian Alai, David W. Goodman, Lenard A. Adler, Joel Shields and Stephen V. Faraone in Journal of Attention Disorders

Supplemental material, sj-docx-1-jad-10.1177_10870547221146256 for Machine Learning and MRI-based Diagnostic Models for ADHD: Are We There Yet? by Yanli Zhang-James, Ali Shervin Razavi, Martine Hoogman, Barbara Franke and Stephen V. Faraone in Journal of Attention Disorders

Contains fulltext : 293473.pdf (Publisher’s version ) (Open Access) Knowledge on psychiatric comorbidity in adult ADHD is essential for prevention, detection, and treatment of these conditions. This review (1) focuses on large studies (n > 10,000; surveys, claims data, population registries) to identify (a) overall, (b) sex- and (c) age-specific patterns of comorbidity of anxiety disorders (ADs), major depressive disorder (MDD), bipolar disorder (BD) and substance use disorders (SUDs) in adults with ADHD relative to adults without ADHD; and (2) describes methodological challenges relating to establishing comorbidity in ADHD in adults as well as priorities for future research. Meta-analyses (ADHD: n = 550,748; no ADHD n = 14,546,814) yielded pooled odds ratios of 5.0(CI:3.29-7.46) for ADs, 4.5(CI:2.44-8.34) for MDD, 8.7(CI:5.47-13.89) for BD and 4.6(CI:2.72-7.80) for SUDs, indicating strong differences in adults with compared to adults without ADHD. Moderation by sex was not found: high comorbidity held for both men and women with sex-specific patterns as in the general population: higher prevalences of ADs, MDD and BD in women and a higher prevalence of SUDs in men. Insufficient data on different phases of the adult lifespan prevented conclusions on developmental changes in comorbidity. We discuss methodological challenges, knowledge gaps, and future research priorities. 01 augustus 2023

Supplemental material, sj-docx-1-jad-10.1177_10870547221146256 for Machine Learning and MRI-based Diagnostic Models for ADHD: Are We There Yet? by Yanli Zhang-James, Ali Shervin Razavi, Martine Hoogman, Barbara Franke and Stephen V. Faraone in Journal of Attention Disorders

Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, with a global prevalence of 2-7% in children and 2.5% in adults.1 Pharmacological treatment is a key component of evidence-based care for individuals with ADHD and the use of ADHD medication has increased markedly across all age groups.2 Stimulants have generally been recommended as first-line pharmacologic treatment and non-stimulants as second line, for school-aged children, adolescents, and adults.2,3 Many randomized controlled trials (RCTs) and observational studies demonstrated short-term beneficial effects of ADHD medications in reducing the core symptoms of ADHD and improving behavioral and neuropsychiatric outcomes (e.g., reducing the risk of injuries, motor vehicle accidents, substance use disorder and improving education outcomes such as test scores).4 Due to the chronic nature of ADHD, long-term pharmacotherapy is typically required. However, in adults, ADHD often goes untreated and leads to impairments in multiple domains.5 Despite the well-known effectiveness of ADHD medications, treatment discontinuation is very common.6 Nearly 50% of individuals with ADHD discontinue treatment within 2–3 years of starting pharmacologic therapy or do not adhere to treatment guidelines.6,7 Non-adherence to medication among individuals with ADHD is suspected to be a major barrier to positive treatment outcomes. In the short-term, non-adherence could affect the tolerability and efficacy of the treatments; and in the long-term, entail poor outcomes and continued impairments in many domains.8 Although there is a growing literature focusing on ADHD over the life span, relatively little is known about the patterns of treatment as people with ADHD grow older. Moreover, despite largely similar treatment guidelines, the use of ADHD medication varies significantly between countries.2,9 An international comparison of medication discontinuation will reveal how these differences extend into the adult population, and will inform clinical practice. References: 1. Faraone SV, Asherson P, Banaschewski T, et al. Attention-deficit/hyperactivity disorder. Nat Rev Dis Primers 2015; 1: 15020. 2. Cortese S. Pharmacologic Treatment of Attention Deficit-Hyperactivity Disorder. The New England journal of medicine 2020; 383(11): 1050-6. 3. Chan E, Fogler JM, Hammerness PG. Treatment of attention-deficit/hyperactivity disorder in adolescents: a systematic review. Jama 2016; 315(18): 1997-2008. 4. Chang Z, Ghirardi L, Quinn PD, Asherson P, D’Onofrio BM, Larsson H. Risks and Benefits of Attention-Deficit/Hyperactivity Disorder Medication on Behavioral and Neuropsychiatric Outcomes: A Qualitative Review of Pharmacoepidemiology Studies Using Linked Prescription Databases. Biological Psychiatry 2019; 86(5): 335-43. 5. Jain R, Jain S, Montano CB. Addressing Diagnosis and Treatment Gaps in Adults With Attention-Deficit/Hyperactivity Disorder. The primary care companion for CNS disorders 2017; 19(5). 6. Gajria K, Lu M, Sikirica V, et al. Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder - a systematic literature review. Neuropsychiatr Dis Treat 2014; 10: 1543-69. 7. Adler LD, Nierenberg AA. Review of Medication Adherence in Children and Adults with ADHD. Postgraduate medicine 2010; 122(1): 184-91. 8. Ferrin M, Taylor E. Child and caregiver issues in the treatment of attention deficit–hyperactivity disorder: education, adherence and treatment choice. Future Neurology 2011; 6(3): 399-413. 9. Bachmann CJ, Wijlaars LP, Kalverdijk LJ, et al. Trends in ADHD medication use in children and adolescents in five western countries, 2005–2012. European Neuropsychopharmacology 2017; 27(5): 484-93.

Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer's disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast "resilient" unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk.

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.

Supplemental material, sj-docx-1-jad-10.1177_10870547221129305 for Association Between ADHD and COVID-19 Infection and Clinical Outcomes: A Retrospective Cohort Study From Electronic Medical Records by Kathleen P. Heslin, Aminat Haruna, Regina A. George, Shiyu Chen, Ishak Nobel, Kathryn B. Anderson, Stephen V. Faraone and Yanli Zhang-James in Journal of Attention Disorders

Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk.

Supplemental material, sj-docx-1-jad-10.1177_10870547221129305 for Association Between ADHD and COVID-19 Infection and Clinical Outcomes: A Retrospective Cohort Study From Electronic Medical Records by Kathleen P. Heslin, Aminat Haruna, Regina A. George, Shiyu Chen, Ishak Nobel, Kathryn B. Anderson, Stephen V. Faraone and Yanli Zhang-James in Journal of Attention Disorders

ObjectiveSome studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.MethodsWe analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.ResultsThere was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t=2.1, p=.04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t=2.7, p=.01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.ConclusionPrior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

Hintergrund: Eine Aufmerksamkeitsdefizit-/Hyperaktivit��tsst��rung (ADHS) im Kindesalter stellt einen Risikofaktor f��r Substanzmissbrauch und St��rungen durch Substanzgebrauch (Substance Use Disorder, SUD) in der Pubert��t und dem (fr��hen) Erwachsenenalter dar. ADHS und SUD treten auch h��ufig bei therapiesuchenden Jugendlichen auf, was die Diagnosestellung und Therapie erschwert sowie mit schlechten Behandlungsergebnissen verbunden ist. Forschungsergebnisse ��ber die Wirkung der Behandlung von ADHS im Kindesalter auf die Pr��vention von SUD im Jugendalter sind nicht eindeutig und Studien ��ber die Diagnose und Behandlung von Jugendlichen mit ADHS und SUD sind selten. Daher reicht die verf��gbare Evidenz allgemein nicht aus, um starke Behandlungsempfehlungen zu rechtfertigen. Fragestellung: Ziel dieser Arbeit war es, eine Konsenserkl��rung auf der Grundlage von wissenschaftlichen Daten und klinischen Erfahrungen zu erhalten. Methodik: Es wurde eine modifizierte Delphi-Studie durchgef��hrt, um basierend auf der Kombination von wissenschaftlichen Daten und klinischer Erfahrung mit einer multidisziplin��ren Gruppe von 55 Expert_innen aus 17 L��ndern einen Konsens zu erzielen. Die Expert_innen wurden gebeten, eine Reihe von Aussagen ��ber die Wirkung der Behandlung von ADHS im Kindesalter auf die SUD bei Jugendlichen sowie ��ber das Screening, die Diagnostik und die Behandlung von Jugendlichen mit komorbidem ADHS und SUD zu bewerten. Ergebnisse: Nach drei iterativen Bewertungsrunden und der Anpassung von 37 Aussagen wurde ein Konsens ��ber 36 dieser Aussagen erzielt, die sechs Bereiche repr��sentieren: allgemein (n = 4), Risiko der Entwicklung einer SUD (n = 3), Screening und Diagnostik (n = 7), psychosoziale Behandlung (n = 5), pharmakologische Behandlung (n = 11) und komplement��re Behandlungen (n = 7). Der Einsatz von Routinescreenings auf ADHS wird bei adoleszenten Patient_innen in einer Suchtbehandlung ebenso wie Routinescreenings auf SUD bei jugendlichen Patient_innen mit ADHS in allgemeinpsychiatrischen Therapiesettings empfohlen. Langwirksame Stimulanzien werden als Behandlung der ersten Wahl von ADHS bei Jugendlichen mit gleichzeitiger ADHS und SUD empfohlen. Die Pharmakotherapie sollte vorzugsweise in psychosoziale Behandlung eingebettet werden. Die einzige nichtkonsentierte Aussage betraf die Notwendigkeit von Abstinenz vor Beginn einer pharmakologischen Behandlung bei Jugendlichen mit ADHS und gleichzeitigem SUD. Im Gegensatz zur Mehrheit verlangten einige Expert_innen eine vollst��ndige Abstinenz vor Beginn einer pharmakologischen Behandlung, einige waren gegen die Verwendung von Stimulanzien bei der Behandlung dieser Patient_innen (unabh��ngig von Abstinenz), w��hrend einige sich gegen die alternative Anwendung von Bupropion aussprachen. Schlussfolgerungen: Diese internationale Konsenserkl��rung kann von Kliniker_innen und Patient_innen zusammen in einem gemeinsamen Entscheidungsprozess genutzt werden, um die besten Interventionen auszuw��hlen und die bestm��glichen Ergebnisse bei adoleszenten Patient_innen mit gleichzeitiger ADHS und SUD zu erzielen.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior., ADHD is often found to be comorbid with disruptive behavior disorders, but the genetic loci underlying this comorbidity are unknown. Here, the authors have performed a GWAS meta-analysis of ADHD with disruptive behavior disorders, finding three genome-wide significant loci in Europeans, and replicating one in a Chinese cohort.

ObjectiveAttention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.MethodsStructural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).ResultsNo shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.ConclusionsThe study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

Objective This study aims to assess the validity of the ADHD module of the Mini-International Neuropsychiatric Interview (MINI-Plus) in patients with substance use disorders (SUD), using the Conners’ Adult ADHD Diagnostic Interview for DSM-IV (CAADID) as the external criterion. Method A cross sectional international multi-center study in 10 countries was conducted in treatment seeking SUD patients. A sample of 1263 patients with both MINI-Plus and CAADID was analyzed to determine the psychometric properties of the MINI-Plus. Results According to the CAADID, 179 patients (14.2%) met criteria for adult ADHD, whereas according to the MINI-Plus 227 patients (18.0%) were identified as having adult ADHD. Sensitivity of the MINI-Plus ADHD module was 74%, specificity was 91%, positive predictive value was 60% and negative predictive value was 96%. Kappa was 0.60. Conclusion The MINI-Plus has acceptable criterion validity for the screening of adult ADHD in treatment seeking SUD patients. Scientific significance On the basis of the results, The MINI-Plus may be used for the screening of ADHD in SUD patients.

Alzheimer's disease is one of the diseases that mostly affects older people without being a part of aging. The most common symptoms include problems with communicating and abstract thinking, as well as disorientation. It is important to detect Alzheimer's disease in early stages so that cognitive functioning would be improved by medication and training. In this paper, we propose two attention model networks for detecting Alzheimer's disease from MRI images to help early detection efforts at the preclinical stage. We also compare the performance of these two attention network models with a baseline model. Recently available OASIS-3 Longitudinal Neuroimaging, Clinical, and Cognitive Dataset is used to train, evaluate and compare our models. The novelty of this research resides in the fact that we aim to detect Alzheimer's disease when all the parameters, physical assessments, and clinical data state that the patient is healthy and showing no symptoms, Comment: 10 pages, 5 figures

Additional file 2: Table S2. Results of Cognitive correlates in relation to ADHD and high intelligence.

Additional file 1: Table S1. Description of cognitive assessment.

Supplemental material, Supplemental_material for Prescription Stimulant Nonmedical Use Among Adolescents Evaluated for Substance Use Disorder Treatment (CHAT™) by Suzanne K. Vosburg, Stephen V. Faraone, Jeffrey H. Newcorn, Anthony L. Rostain, Robert L. Findling, Stephen F. Butler, Taryn Dailey Govoni and Jody L. Green in Journal of Attention Disorders

Supplemental material, Supplemental_Material for An innovative SMS intervention to improve adherence to stimulants in children with ADHD: Preliminary findings by Ronna Fried, Maura DiSalvo, Caroline Kelberman, Amos Adler, Debra McCafferty, K Yvonne Woodworth, Allison Green, Itai Biederman, Stephen V Faraone and Joseph Biederman in Journal of Psychopharmacology

Supplemental material, Supplemental_material for Prescription Stimulant Nonmedical Use Among Adolescents Evaluated for Substance Use Disorder Treatment (CHAT™) by Suzanne K. Vosburg, Stephen V. Faraone, Jeffrey H. Newcorn, Anthony L. Rostain, Robert L. Findling, Stephen F. Butler, Taryn Dailey Govoni and Jody L. Green in Journal of Attention Disorders

Supplemental material, sj-pdf-1-jad-10.1177_1087054720978549 for Physical Health, Media Use, and Mental Health in Children and Adolescents With ADHD During the COVID-19 Pandemic in Australia by Emma Sciberras, Pooja Patel, Mark A. Stokes, David Coghill, Christel M. Middeldorp, Mark A. Bellgrove, Stephen P. Becker, Daryl Efron, Argyris Stringaris, Stephen V. Faraone, Susannah T. Bellows, Jon Quach, Tobias Banaschewski, Jane McGillivray, Delyse Hutchinson, Tim J. Silk, Glenn Melvin, Amanda G. Wood, Anna Jackson, George Loram, Lidia Engel, Alicia Montgomery and Elizabeth Westrupp in Journal of Attention Disorders

Supplemental material, sj-pdf-1-jad-10.1177_1087054720978549 for Physical Health, Media Use, and Mental Health in Children and Adolescents With ADHD During the COVID-19 Pandemic in Australia by Emma Sciberras, Pooja Patel, Mark A. Stokes, David Coghill, Christel M. Middeldorp, Mark A. Bellgrove, Stephen P. Becker, Daryl Efron, Argyris Stringaris, Stephen V. Faraone, Susannah T. Bellows, Jon Quach, Tobias Banaschewski, Jane McGillivray, Delyse Hutchinson, Tim J. Silk, Glenn Melvin, Amanda G. Wood, Anna Jackson, George Loram, Lidia Engel, Alicia Montgomery and Elizabeth Westrupp in Journal of Attention Disorders

Supplemental material, Supplemental_Material for An innovative SMS intervention to improve adherence to stimulants in children with ADHD: Preliminary findings by Ronna Fried, Maura DiSalvo, Caroline Kelberman, Amos Adler, Debra McCafferty, K Yvonne Woodworth, Allison Green, Itai Biederman, Stephen V Faraone and Joseph Biederman in Journal of Psychopharmacology

Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary-level data from previous genome-wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune-related phenotypes. We estimated heritability and examined pair-wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods. Using LDSC, we observed significant genetic correlations between immune-related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit-hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome-wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations among the immune-related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study.

Attention-deficit hyperactivity disorder (ADHD) is a complex polygenic disorder. This study aimed to discover common and rare DNA variants associated with ADHD in a large homogeneous Han Chinese ADHD case-control sample. The sample comprised 1,040 cases and 963 controls. All cases met DSM-IV ADHD diagnostic criteria. We used the Affymetrix6.0 array to assay both single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Genome-wide association analyses were performed using PLINK. SNP-heritability and SNP-genetic correlations with ADHD in Caucasians were estimated with genome-wide complex trait analysis (GCTA). Pathway analyses were performed using the Interval enRICHment Test (INRICH), the Disease Association Protein-Protein Link Evaluator (DAPPLE), and the Genomic Regions Enrichment of Annotations Tool (GREAT). We did not find genome-wide significance for single SNPs but did find an increased burden of large, rare CNVs in the ADHD sample (P=0.038). SNP-heritability was estimated to be 0.42 (standard error, 0.13, P=0.0017) and the SNP-genetic correlation with European Ancestry ADHD samples was 0.39 (SE 0.15, P=0.0072). The INRICH, DAPPLE, and GREAT analyses implicated several gene ontology cellular components, including neuron projections and synaptic components, which are consistent with a neurodevelopmental pathophysiology for ADHD. This study suggested the genetic architecture of ADHD comprises both common and rare variants. Some common causal variants are likely to be shared between Han Chinese and Caucasians. Complex neurodevelopmental networks may underlie ADHD's etiology. (c) 2013 Wiley Periodicals, Inc. Refereed/Peer-reviewed

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.Significance StatementLeft-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.

The Psychiatric Genomics Consortium (PGC) is the largest consortium in the history of psychiatry. This global effort is dedicated to rapid progress and open science, and in the past decade it has delivered an increasing flow of new knowledge about the fundamental basis of common psychiatric disorders. The PGC has recently commenced a program of research designed to deliver "actionable" findings-genomic results that 1) reveal fundamental biology, 2) inform clinical practice, and 3) deliver new therapeutic targets. The central idea of the PGC is to convert the family history risk factor into biologically, clinically, and therapeutically meaningful insights. The emerging findings suggest that we are entering a phase of accelerated genetic discovery for multiple psychiatric disorders. These findings are likely to elucidate the genetic portions of these truly complex traits, and this knowledge can then be mined for its relevance for improved therapeutics and its impact on psychiatric practice within a precision medicine framework. [AJP at 175: Remembering Our Past As We Envision Our Future November 1946: The Genetic Theory of Schizophrenia Franz Kallmann's influential twin study of schizophrenia in 691 twin pairs was the largest in the field for nearly four decades. (Am J Psychiatry 1946; 103:309-322 )].

IMPORTANCE: Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. OBJECTIVES: To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association data from 5 large population-based cohorts and 3 target samples with genome-wide genotype and ASB data were used for meta-analysis from March 1, 2014, to May 1, 2016. All data sets used quantitative phenotypes, except for the Finnish Crime Study, which applied a case-control design (370 patients and 5850 control individuals). MAIN OUTCOME AND MEASURES: This study adopted relatively broad inclusion criteria to achieve a quantitative measure of ASB derived from multiple measures, maximizing the sample size over different age ranges. RESULTS: The discovery samples comprised 16 400 individuals, whereas the target samples consisted of 9381 individuals (all individuals were of European descent), including child and adult samples (mean age range, 6.7-56.1 years). Three promising loci with sex-discordant associations were found (8535 female individuals, chromosome 1: rs2764450, chromosome 11: rs11215217; 7772 male individuals, chromosome X, rs41456347). Polygenic risk score analyses showed prognostication of antisocial phenotypes in an independent Finnish Crime Study (2536 male individuals and 3684 female individuals) and shared genetic origin with conduct problems in a population-based sample (394 male individuals and 431 female individuals) but not with conduct disorder in a substance-dependent sample (950 male individuals and 1386 female individuals) (R2 = 0.0017 in the most optimal model, P = 0.03). Significant inverse genetic correlation of ASB with educational attainment (r = -0.52, P = .005) was detected. CONCLUSIONS AND RELEVANCE: The Broad Antisocial Behavior Consortium entails the largest collaboration to date on the genetic architecture of ASB, and the first results suggest that ASB may be highly polygenic and has potential heterogeneous genetic effects across sex.

BackgroundAttention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently co-occurring and highly heritable mental health conditions. We hypothesized that BPD cases with an early age of onset (≤21 years old) would be particularly likely to show genetic covariation with ADHD.MethodsGenome-wide association study data were available for 4609 individuals with ADHD, 9650 individuals with BPD (5167 thereof with early-onset BPD), and 21,363 typically developing controls. We conducted a cross-disorder genome-wide association study meta-analysis to identify whether the observed comorbidity between ADHD and BPD could be due to shared genetic risks.ResultsWe found a significant single nucleotide polymorphism-based genetic correlation between ADHD and BPD in the full and age-restricted samples (rGfull = .64, p = 3.13 × 10-14; rGrestricted = .71, p = 4.09 × 10-16). The meta-analysis between the full BPD sample identified two genome-wide significant (prs7089973 = 2.47 × 10-8; prs11756438 = 4.36 × 10-8) regions located on chromosomes 6 (CEP85L) and 10 (TAF9BP2). Restricting the analyses to BPD cases with an early onset yielded one genome-wide significant association (prs58502974 = 2.11 × 10-8) on chromosome 5 in the ADCY2 gene. Additional nominally significant regions identified contained known expression quantitative trait loci with putative functional consequences for NT5DC1, NT5DC2, and CACNB3 expression, whereas functional predictions implicated ABLIM1 as an allele-specific expressed gene in neuronal tissue.ConclusionsThe single nucleotide polymorphism-based genetic correlation between ADHD and BPD is substantial, significant, and consistent with the existence of genetic overlap between ADHD and BPD, with potential differential genetic mechanisms involved in early and later BPD onset.

Objectives: Investigation of the genetic basis of endophenotype and analysis the pathways with multiple genes of small effects might increase the understanding of the genetic basis of attention deficit hyperactivity disorder (ADHD). Here we aimed to explore the genetic basis of cognitive flexibility in ADHD at SNP, gene and pathway level. Methods: The Trail-Making Test (TMT) was used to test the cognitive flexibility of 788 ADHD patients. A genome-wide association analysis of cognitive flexibility was conducted for 644,166 single nucleotide polymorphisms (SNPs). Results: The top SNP rs2049161 (P = 5.08e-7) involved gene DLGAP1 and the top gene CADPS2 in the gene-based analysis obtained much literature evidence to be associated with psychiatric disorders. Gene expression and network analysis showed their contribution to cognition function. The interval enrichment analysis highlighted potential contribution of ‘adenylate cyclase activity’ and ADCY2 to cognitive flexibility. Candidate pathway-based analysis for all SNPs found glutamate system, neurite outgrowth and noradrenergic system related pathways were significantly associated with cognitive flexibility (FDR < 0.05), among which the neurite outgrowth pathway was also associated with ADHD symptoms. Conclusions: This study provides evidence for the genes and pathways associated with cognitive flexibility and facilitate the uncovering of the genetic basis of ADHD.

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) often co-occur. Both are highly heritable; however, it has been difficult to discover genetic risk variants. Glutamate and GABA are main excitatory and inhibitory neurotransmitters in the brain; their balance is essential for proper brain development and functioning. In this study we investigated the role of glutamate and GABA genetics in ADHD severity, autism symptom severity and inhibitory performance, based on gene set analysis, an approach to investigate multiple genetic variants simultaneously. Common variants within glutamatergic and GABAergic genes were investigated using the MAGMA software in an ADHD case-only sample (n=931), in which we assessed ASD symptoms and response inhibition on a Stop task. Gene set analysis for ADHD symptom severity, divided into inattention and hyperactivity/impulsivity symptoms, autism symptom severity and inhibition were performed using principal component regression analyses. Subsequently, gene-wide association analyses were performed. The glutamate gene set showed an association with severity of hyperactivity/impulsivity (P=0.009), which was robust to correcting for genome-wide association levels. The GABA gene set showed nominally significant association with inhibition (P=0.04), but this did not survive correction for multiple comparisons. None of single gene or single variant associations was significant on their own. By analyzing multiple genetic variants within candidate gene sets together, we were able to find genetic associations supporting the involvement of excitatory and inhibitory neurotransmitter systems in ADHD and ASD symptom severity in ADHD.

Objective: To examine the factor structure of attention-deficit/ hyperactivity disorder (ADHD) in a clinical sample of 1,373 children and adolescents with ADHD and their 1,772 unselected siblings recruited from different countries across a large age range. Hierarchical and correlated factor analytic models were compared separately in the ADHD and sibling samples, across three different instruments and across parent and teacher informants. Specific consideration was given to factorial invariance analyses across different ages and different countries in the ADHD sample. Method: A sample of children and adolescents between 5 and 17 years of age with ADHD and their unselected siblings was assessed. Participants were recruited from seven European countries and Israel. ADHD symptom data came from a clinical interview with parents Parental Account of Childhood Symptoms and questionnaires from parents and teachers (Conners Parent and Teacher). Results: A hierarchical general factor model with two specific factors best represented the structure of ADHD in both the ADHD and unselected sibling groups, and across informants and instruments. The model was robust and invariant with regard to age differences in the ADHD sample. The model was not strongly invariant across different national groups in the ADHD sample, likely reflecting severity differences across the different centers and not any substantial difference in the clinical presentation of ADHD. Conclusions: The results replicate previous studies of a model with a unitary ADHD component and separable specific traits of inattention and hyperactivity/impulsivity. The unique contribution of this study was finding support for this model across a large developmental and multinational/multicultural sample and its invariance across ages. © 2011 Association for Child and Adolescent Mental Health.

Genetic associations involving both rare and common alleles have been reported for schizophrenia but there have been no systematic scans for rare recessive genotypes using fully phased trio data. Here, we use exome sequencing in 604 schizophrenia proband–parent trios to investigate the role of recessive (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder. The burden of recessive genotypes was not significantly increased in probands at either a genome-wide level or in any individual gene after adjustment for multiple testing. At a system level, probands had an excess of nonsynonymous compound heterozygous genotypes (minor allele frequency, MAF ⩽1%) in voltage-gated sodium channels (VGSCs; eight in probands and none in parents, P=1.5 × 10−4). Previous findings of multiple de novo loss-of-function mutations in this gene family, particularly SCN2A, in autism and intellectual disability provide biological and genetic plausibility for this finding. Pointing further to the involvement of VGSCs in schizophrenia, we found that these genes were enriched for nonsynonymous mutations (MAF ⩽0.1%) in cases genotyped using an exome array, (5585 schizophrenia cases and 8103 controls), and that in the trios data, synaptic proteins interacting with VGSCs were also enriched for both compound heterozygosity (P=0.018) and de novo mutations (P=0.04). However, we were unable to replicate the specific association with compound heterozygosity at VGSCs in an independent sample of Taiwanese schizophrenia trios (N=614). We conclude that recessive genotypes do not appear to make a substantial contribution to schizophrenia at a genome-wide level. Although multiple lines of evidence, including several from this study, suggest that rare mutations in VGSCs contribute to the disorder, in the absence of replication of the original findings regarding compound heterozygosity, this conclusion requires evaluation in a larger sample of trios.

Item does not contain fulltext BACKGROUNd: Emotional lability (EL) is commonly seen in patients with attention-deficit/hyperactivity disorder (ADHD). The reasons for this association remain currently unknown. To address this question, we examined the relationship between ADHD and EL symptoms, and performance on a range of neuropsychological tasks to clarify whether EL symptoms are predicted by particular cognitive and/or motivational dysfunctions and whether these associations are mediated by the presence of ADHD symptoms. METHODS: A large multi-site sample of 424 carefully diagnosed ADHD cases and 564 unaffected siblings and controls aged 6-18 years performed a broad neuropsychological test battery, including a Go/No-Go Task, a warned four-choice Reaction Time task, the Maudsley Index of Childhood Delay Aversion and Digit span backwards. Neuropsychological variables were aggregated as indices of processing speed, response variability, executive functions, choice impulsivity and the influence of energetic and/or motivational factors. EL and ADHD symptoms were regressed on each neuropsychological variable in separate analyses controlling for age, gender and IQ, and, in subsequent regression analyses, for ADHD and EL symptoms respectively. RESULTS: Neuropsychological variables significantly predicted ADHD and EL symptoms with moderate-to-low regression coefficients. However, the association between neuropsychological parameters on EL disappeared entirely when the effect of ADHD symptoms was taken into account, revealing that the association between the neuropsychological performance measures and EL is completely mediated statistically by variations in ADHD symptoms. Conversely, neuropsychological effects on ADHD symptoms remained after EL symptom severity was taken into account. CONCLUSIONS: The neuropsychological parameters examined, herein, predict ADHD more strongly than EL. They cannot explain EL symptoms beyond what is already accounted for by ADHD symptom severity. The association between EL and ADHD cannot be explained by these cognitive or motivational deficits. Alternative mechanisms, including overlapping genetic influences (pleiotropic effects) and/or alternative neuropsychological processes need to be considered.

Udgivelsesdato: 2009-May Children with attention deficit/hyperactivity disorder (ADHD) choose smaller sooner (SS) over larger later (LL) rewards more than controls. Here we assess the contributions of impulsive drive for immediate rewards (IDIR) and delay aversion (DAv) to this pattern. We also explore the characteristics of, and the degree of familiality in, ADHD SS responders. We had 360 ADHD probands; 349 siblings and 112 controls (aged between 6 to 17 years) chose between SS (1 point after 2 s) and LL reward (2 points after 30 s) outcomes on the Maudsley Index of Delay Aversion (Kuntsi, Oosterlaan, & Stevenson, 2001): Under one condition SS choice led to less overall trial delay under another it did not. ADHD participants chose SS more than controls under both conditions. This effect was larger when SS choice reduced trial delay. ADHD SS responders were younger, had lower IQ, more conduct disorder and had siblings who were more likely to be SS responders themselves. The results support a dual component model in which both IDIR and DAv contribute to SS choice in ADHD. SS choice may be a marker of an ADHD motivational subtype.

Background: ADHD is a common and complex genetic disorder.Genetic risk factors are expected to be multiple, have small effect sizes when considered individually and to interact with each other and with environmental factors. Objective: To describe the difficulties involved in the genetic investigation of such a complex disorder and give a prospective for the future. Methods: Review based on empirical literature and project description. Results: considerable progress has been achieved through the association analysis of candidate gene loci. Linkage scans using affected sibling pairs have identified a number of potential loci that may lead to the identification of novel genes of moderate effect size. Quantitative trait locus (QTL approaches provide powerful complementary strategies that have the potential to link the categorical disorder to continuously distributed traits associated more closely with underlying genetic liability in the general population. Success in identifying some associated genes has been complemented by functional studies that seek to understand the mode of action of such genes. Conclusion: Progress in understanding the mechanisms involved has not been straightforward and many inconsistencies have arisen. In order to take advantage of the potential for progress that stems from the genetic findings it will be important to draw upon a variety of approaches and experimental paradigms. A functional genomic approach to ADHD means that investigation of gene function is carried out at various levels of analysis, not only at the level of molecular and cellular function but also at the level of psychological processes, neuronal networks, environmental interactions and behavioural outcomes

The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders.

The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders.

The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders.

IMPORTANCE: Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. OBJECTIVES: To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association data from 5 large population-based cohorts and 3 target samples with genome-wide genotype and ASB data were used for meta-analysis from March 1, 2014, to May 1, 2016. All data sets used quantitative phenotypes, except for the Finnish Crime Study, which applied a case-control design (370 patients and 5850 control individuals). MAIN OUTCOME AND MEASURES: This study adopted relatively broad inclusion criteria to achieve a quantitative measure of ASB derived from multiple measures, maximizing the sample size over different age ranges. RESULTS: The discovery samples comprised 16 400 individuals, whereas the target samples consisted of 9381 individuals (all individuals were of European descent), including child and adult samples (mean age range, 6.7-56.1 years). Three promising loci with sex-discordant associations were found (8535 female individuals, chromosome 1: rs2764450, chromosome 11: rs11215217; 7772 male individuals, chromosome X, rs41456347). Polygenic risk score analyses showed prognostication of antisocial phenotypes in an independent Finnish Crime Study (2536 male individuals and 3684 female individuals) and shared genetic origin with conduct problems in a population-based sample (394 male individuals and 431 female individuals) but not with conduct disorder in a substance-dependent sample (950 male individuals and 1386 female individuals) (R2 = 0.0017 in the most optimal model, P = 0.03). Significant inverse genetic correlation of ASB with educational attainment (r = -0.52, P = .005) was detected. CONCLUSIONS AND RELEVANCE: The Broad Antisocial Behavior Consortium entails the largest collaboration to date on the genetic architecture of ASB, and the first results suggest that ASB may be highly polygenic and has potential heterogeneous genetic effects across sex.