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

Arch Gen Psychiatry. 2008 Feb;65(2):203-10. doi: 10.1001/archgenpsychiatry.2007.24.


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 Val158Met) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adolescent
  • Adult
  • Aggression / psychology
  • Antisocial Personality Disorder / diagnosis
  • Antisocial Personality Disorder / genetics*
  • Antisocial Personality Disorder / psychology
  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Catechol O-Methyltransferase / genetics*
  • Child
  • Child, Preschool
  • Codon / genetics
  • Cohort Studies
  • Conduct Disorder / diagnosis
  • Conduct Disorder / genetics
  • Conduct Disorder / psychology
  • Crime / psychology
  • Diseases in Twins / genetics
  • Diseases in Twins / psychology
  • England
  • Female
  • Genetic Carrier Screening
  • Genetic Predisposition to Disease / genetics
  • Genotype*
  • Homozygote
  • Humans
  • Longitudinal Studies
  • Male
  • Methionine / genetics
  • New Zealand
  • Phenotype
  • Polymorphism, Genetic / genetics
  • Reproducibility of Results
  • Valine / genetics
  • Wales


  • Codon
  • Methionine
  • Catechol O-Methyltransferase
  • Valine