We investigated gene–environment (G × E) interactions related to childhood antisocial behavior between polymorphisms implicated by recent genome-wide association studies (GWASs) and two key environmental adversities (maltreatment and smoking during pregnancy) in a large population cohort (ALSPAC). We also studied the MAOA candidate gene and addressed comorbid attention-deficit/hyperactivity disorder (ADHD). ALSPAC is a large, prospective, ethnically homogeneous British cohort. Our outcome consisted of mother-rated conduct disorder symptom scores at age 7;9 years. G × E interactions were tested in a sex-stratified way (α = 0.0031) for four GWAS-implicated variants (for males, rs4714329 and rs9471290; for females, rs2764450 and rs11215217), and a length polymorphism near the MAOA-promoter region. We found that males with rs4714329-GG (P = 0.0015) and rs9471290-AA (P = 0.0001) genotypes were significantly more susceptible to effects of smoking during pregnancy in relation to childhood antisocial behavior. Females with the rs11215217-TC genotype (P = 0.0018) were significantly less susceptible to effects of maltreatment, whereas females with the MAOA-HL genotype (P = 0.0002) were more susceptible to maltreatment effects related to antisocial behavior. After adjustment for comorbid ADHD symptomatology, aforementioned G × E’s remained significant, except for rs11215217 × maltreatment, which retained only nominal significance. Genetic variants implicated by recent GWASs of antisocial behavior moderated associations of smoking during pregnancy and maltreatment with childhood antisocial behavior in the general population. While we also found a G × E interaction between the candidate gene MAOA and maltreatment, we were mostly unable to replicate the previous results regarding MAOA–G × E’s. Future studies should, in addition to genome-wide implicated variants, consider polygenic and/or multimarker analyses and take into account potential sex stratification.

Antisocial and aggressive behaviors show considerable heritability and are central to disruptive behavior disorders (DBDs), but are also frequently observed in attention deficit hyperactivity disorder (ADHD). While the amygdala is implicated as a key neural structure, it remains unclear whether common genetic variants underlie this brain-behavior association. We hypothesized that polygenic (risk) scores for antisocial and aggressive behaviors (ASB-PRS) would be related to amygdala morphology. Using the Broad Antisocial Behavior Consortium genome-wide association study (GWAS; mostly population based cohorts), we calculated ASB-PRS in the NeuroIMAGE I ADHD case-control sample with varying levels of DBD symptomatology (n=679 from 379 families, aged 7 - 29). We first investigated associations of several ASB-PRS p value thresholds with the presence of DBD symptoms and self-reported antisocial behavior (ASB) to determine the threshold for further analyses. This PRS was then related to amygdala volume and shape using regression and vertex-wise analyses. Our results showed associations of ASB-PRS with the presence of DBD symptoms, self-reported ASB, and left basolateral amygdala shape, independent of ADHD symptom severity and ADHD-PRS, with a relative outward displacement of the vertices. No associations of ASB-PRS, DBD symptoms or self-reported ASB with amygdala volume were found. Our results indicate that genetic risk for antisocial and aggressive behaviors is related to amygdala shape alterations, and point to genetic sharing across different DBD and ASB and aggression-related phenotypes as a spectrum of genetically related quantitative traits. Additionally, our findings support the utility of vertex-based shape analyses in genetic studies of ASB, aggression, and DBDs.

To provide a comprehensive overview of the prevalence and comorbidity patterns of mental disorders in a large child and adolescent psychiatry sample. Data on DSM diagnoses were retrieved from medical records of children (0.5-18 years old) who received care at a DREAMS center between 2015 and 2019. DREAMS is a consortium of 4 academic centers for child and adolescent psychiatry in the Netherlands that provide both outpatient and inpatient care. Diagnoses were assigned in regular clinical practice. Between 2015 and 2019, 65,363 children received care at a DREAMS center (mean [SD] age at admission = 10.8 [4.1] years; 60.7% male). Of these children, 46,762 (71.5%) had a registered DSM disorder. The most prevalent primary diagnoses were autism (34.6%), attention-deficit/hyperactivity disorder (24.6%), and trauma and stressor-related disorders (8.4%). Approximately half of all children (47.2%) had at least 1 comorbid diagnosis, of which intellectual disabilities were the most prevalent (29.5%). Diagnostic patterns across sex and age as well as comorbidity patterns were generally consistent with previous research, but the prevalence of autism and attention-deficit/hyperactivity disorder was higher than in other studies. Real-world diagnostic information such as presented here is essential to understand the use of DSM-5 in clinical practice, put differences between contexts and countries into perspective, and ultimately improve our diagnostic protocols and treatments.