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Avshalom Caspi, PhD; Kate Langley, PhD; Barry Milne, MSc; Terrie E. Moffitt, PhD; Michael O’Donovan, MD; Michael J. Owen, MD; Monica Polo Tomas, MSc; Richie Poulton, PhD; Michael Rutter, MD; Alan Taylor, MSc; Benjamin Williams, BSc; Anita Thapar, MD

Arch Gen Psychiatry. 2008;65(2):203-210.

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.

Author Affiliations: Medical Research Council Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, England (Drs Caspi, Moffitt, and Rutter; Mssrs Milne, Taylor, and Williams; and Ms Polo Tomas); Departments of Psychology & Neuroscience and Psychiatry & Behavioral Sciences, and Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina (Drs Caspi and Moffitt); Department of Psychological Medicine, Cardiff University, Cardiff, Wales (Drs Langley, O’Donovan, Owen, and Thapar); and Dunedin School of Medicine, University of Otago, Dunedin, New Zealand (Dr Poulton).

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