title: Catechol O-methyltransferase gene variant and birth weight predict early-onset antisocial behavior in children with attention-deficit/hyperactivity disorder.
abstract: BACKGROUND
  Early-onset antisocial behavior accompanied by attention-deficit/hyperactivity disorder is a clinically severe variant of antisocial behavior that is associated with a particularly poor outcome. Identifying early predictors is thus important. Genetic and prenatal environmental risk factors and prefrontal cortical function are thought to contribute. Recent evidence suggests that prefrontal cortical function is influenced by a valine/methionine variant in the catechol O-methyltransferase (COMT) gene.
  
  
  OBJECTIVE
  To test the a priori hypothesis that this genetic variant predicts early-onset antisocial behavior in a high-risk sample and further examine the effects of birth weight, an environmentally influenced index of prenatal adversity previously linked to childhood disruptive behaviors and genotype x birth weight interaction.
  
  
  METHODS
  A family-based genetic study was undertaken between 1997 and 2003. Participants were prospectively recruited from child and adolescent psychiatry and child health clinics in the United Kingdom and included 240 clinic children who met diagnostic criteria for attention-deficit/hyperactivity disorder or hyperkinetic disorder. Participants underwent comprehensive standardized assessments including measures of antisocial behavior and IQ. Main Outcome Measure DSM-IV symptoms of childhood-onset conduct disorder rated by trained interviewers using a standard diagnostic interview.
  
  
  RESULTS
  The results show main effects of the COMT gene variant (P = .002), birth weight (P = .002), and a significant gene x environment (COMT x birth weight) interaction (P = .006).
  
  
  CONCLUSIONS
  Early-onset antisocial behavior in a high-risk clinical group is predicted by a specific COMT gene variant previously linked with prefrontal cortical function and birth weight, and those possessing the val/val genotype are more susceptible to the adverse effects of prenatal risk as indexed by lower birth weight.
authors.affiliation: Department of Psychological Medicine, College of Medicine, School of Psychology, Cardiff University, Heath Park, Cardiff, Wales. thapar@cardiff.ac.uk
authors.forename: Anita
authors.initials: A
authors.lastname: Thapar
authors.forename: Kate
authors.initials: K
authors.lastname: Langley
authors.forename: Tom
authors.initials: T
authors.lastname: Fowler
authors.forename: Frances
authors.initials: F
authors.lastname: Rice
authors.forename: Darko
authors.initials: D
authors.lastname: Turic
authors.forename: Naureen
authors.initials: N
authors.lastname: Whittinger
authors.forename: John
authors.initials: J
authors.lastname: Aggleton
authors.forename: Marianne
authors.initials: M
authors.lastname: Van den Bree
authors.forename: Michael
authors.initials: M
authors.lastname: Owen
authors.forename: Michael
authors.initials: M
authors.lastname: O'Donovan
mesh_terms: D000293:Adolescent; D000367:Age Factors; D017668:Age of Onset; D000987:Antisocial Personality Disorder / Q000175:diagnosis / Q000453:epidemiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology*; D001724:Birth Weight / Q000235:genetics* / Q000502:physiology; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D017397:Prefrontal Cortex / Q000201:enzymology* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012044:Regression Analysis; D012307:Risk Factors; D014633:Valine / Q000235:genetics / Q000378:metabolism
chemical_list: D002394:Catechol O-Methyltransferase; D014633:Valine