title: A replicated molecular genetic basis for subtyping antisocial behavior in children with attention-deficit/hyperactivity disorder.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Three independent samples composed of 1 clinical sample of ADHD cases and 2 birth cohort studies.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Medical Research Council Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, England. a.caspi@iop.kcl.ac.uk
authors.forename: Avshalom
authors.initials: A
authors.lastname: Caspi
authors.forename: Kate
authors.initials: K
authors.lastname: Langley
authors.forename: Barry
authors.initials: B
authors.lastname: Milne
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Moffitt
authors.forename: Michael
authors.initials: M
authors.lastname: O'Donovan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Monica
authors.initials: M
authors.lastname: Polo Tomas
authors.forename: Richie
authors.initials: R
authors.lastname: Poulton
authors.forename: Michael
authors.initials: M
authors.lastname: Rutter
authors.forename: Alan
authors.initials: A
authors.lastname: Taylor
authors.forename: Benjamin
authors.initials: B
authors.lastname: Williams
authors.forename: Anita
authors.initials: A
authors.lastname: Thapar
mesh_terms: D000293:Adolescent; D000328:Adult; D000374:Aggression / Q000523:psychology; D000987:Antisocial Personality Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000235:genetics; D015331:Cohort Studies; D019955:Conduct Disorder / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D003415:Crime / Q000523:psychology; D004200:Diseases in Twins / Q000235:genetics / Q000523:psychology; D004739:England; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008715:Methionine / Q000235:genetics; D009520:New Zealand; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D015203:Reproducibility of Results; D014633:Valine / Q000235:genetics; D014852:Wales
chemical_list: D003062:Codon; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine