A Replicated Molecular Genetic Basis for Subtyping Antisocial Behavior in Children With Attention-Deficit/Hyperactivity Disorder
Abstract
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.
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The first published study examining a possible association between COMT and child aggression was in the context of ADHD, where Caspi et al. reported an association among ADHD patients of Val/Val with increased aggression compared to Met-carriers; the association was replicated across three samples within this study.
“The first published study that examined a possible association between COMT gene and child aggression was in the context of ADHD, where Caspi et al. [60] reported an association among ADHD patients of Val/Val with increased aggression compared to Met-carriers; the association was replicated across three samples within this study.”
From Genetics of child aggression, a systematic review (2024) · cites this paper as [60]
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References 50 · Cited by 221
- Authors
- Caspi, A., Langley, K., Milne, B., Moffitt, T. E., O’Donovan, M., Owen, M. J., Polo Tomas, M., Poulton, R., Rutter, M., Taylor, A., Williams, B., & Thapar, A.
- Affiliations
- King's College London (GB)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2008-02-01
- Volume
- 65
- Issue
- 2
- Pages
- 203
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2104037911
- Cited by
- 221
- References
- 50
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 3 · 2018: 7 · 2017: 6 · 2016: 22 · 2015: 17 · 2014: 12 · 2013: 23 · 2012: 25
- FWCI
- 16.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust
- National Institute of Mental Health (MH-49414, MH 45070, R01MH049414, R01MH045070)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Keywords
- attention deficit hyperactivity disorder, antisocial behavior, conduct disorder, catechol-O-methyltransferase, COMT Val158Met polymorphism, genetic heterogeneity, aggression, offending, child psychiatry, birth cohort studies, genetic subtyping
- MeSH terms
- Adolescent, Adult, Aggression, Antisocial Personality Disorder, Attention Deficit Disorder with Hyperactivity, Catechol O-Methyltransferase, Child, Child, Preschool, Codon, Crime, Diseases in Twins, England, Female, Genotype, Genetic Carrier Screening, Homozygote, Humans, Longitudinal Studies, Male, Methionine, New Zealand, Phenotype, Polymorphism, Genetic, Valine, Wales, Reproducibility of Results, Cohort Studies, Conduct Disorder, Genetic Predisposition to Disease
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