A replicated molecular genetic basis for subtyping antisocial behavior in children with attention-deficit/hyperactivity disorder

Context: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder that in some cases is accompanied by antisocial behavior. Objective: To test if variations in the catechol O-methyltransferase gene (COMT) would prove useful in identifying the subset of children with ADHD who exhibit antisocial behavior. Design: Three independent samples composed of 1 clinical sample of ADHD cases and 2 birth cohort studies. Participants: Participants in the clinical sample were drawn from child psychiatry and child health clinics in England and Wales. The 2 birth cohort studies included 1 sample of 2232 British children born in 1994-1995 and a second sample of 1037 New Zealander children born in 1972-1973. Main Outcome Measures: Diagnosis of ADHD and measures of antisocial behavior. Results: We present replicated evidence that the COMT valine/methionine polymorphism at codon 158 (COMT Val(158)Met) was associated with phenotypic variation among children with ADHD. Across the 3 samples, valine/valine homozygotes had more symptoms of conduct disorder, were more aggressive, and were more likely to be convicted of criminal offenses compared with methionine carriers. Conclusions: The findings confirm the presence of genetic heterogeneity in ADHD and illustrate how genetic information may provide biological evidence pointing to clinical subtypes.