A replicated molecular genetic basis for subtyping antisocial behavior in children with attention-deficit/hyperactivity disorder.
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.
Caspi
Avshalom
A
Medical Research Council Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, England. a.caspi@iop.kcl.ac.uk
Langley
Kate
K
Milne
Barry
B
Moffitt
Terrie E
TE
O'Donovan
Michael
M
Owen
Michael J
MJ
Polo Tomas
Monica
M
Poulton
Richie
R
Rutter
Michael
M
Taylor
Alan
A
Williams
Benjamin
B
Thapar
Anita
A
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
D003062:Codon; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine