title: The dopamine D4 receptor gene and moderation of the association between externalizing behavior and IQ.
abstract: BACKGROUND
  Dopaminergic neurotransmission is implicated in externalizing behavior problems, such as aggression and hyperactivity. Externalizing behavior is known to be negatively associated with cognitive ability. Activation of dopamine D4 receptors appears to inhibit the functioning of the prefrontal cortex, a brain region implicated in cognitive ability. The 7-repeat allele of the dopamine D4 receptor gene produces less efficient receptors, relative to other alleles, and this may alter the effects of dopamine on cognitive function.
  
  
  OBJECTIVE
  To examine the influence of a polymorphism in the third exon of the dopamine D4 receptor gene on the association between externalizing behavior and IQ.
  
  
  METHODS
  In 1 community sample and 2 clinical samples, the presence or absence of the 7-repeat allele was examined as a moderator of the association between externalizing behavior and IQ; the strength of this effect across samples was estimated meta-analytically.
  
  
  METHODS
  Eighty-seven boys from a longitudinal community study, 48 boys referred clinically for aggression, and 42 adult males diagnosed with attention-deficit/hyperactivity disorder.
  
  
  METHODS
  IQ scores and observer ratings of externalizing behavior were taken from existing data sets.
  
  
  RESULTS
  Among individuals lacking the 7-repeat allele, externalizing behavior was negatively correlated with IQ (mean r = -0.43; P<.001). Among individuals having at least 1 copy of the 7-repeat allele, externalizing behavior and IQ were uncorrelated (mean r = 0.02; P = .45). The difference between these correlations was significant (z = -2.99; P<.01).
  
  
  CONCLUSIONS
  Allelic variation of the dopamine D4 receptor gene appears to be a genetic factor moderating the association between externalizing behavior and cognitive ability. This finding may help to elucidate the adaptive value of the 7-repeat allele.
authors.affiliation: Department of Psychology, and Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada. cdeyoung@post.harvard.edu
authors.forename: Colin G
authors.initials: CG
authors.lastname: DeYoung
authors.forename: Jordan B
authors.initials: JB
authors.lastname: Peterson
authors.forename: Jean R
authors.initials: JR
authors.lastname: Séguin
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Mejia
authors.forename: Robert O
authors.initials: RO
authors.lastname: Pihl
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Beitchman
authors.forename: Umesh
authors.initials: U
authors.lastname: Jain
authors.forename: Richard E
authors.initials: RE
authors.lastname: Tremblay
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Palmour
mesh_terms: D000293:Adolescent; D000328:Adult; D000374:Aggression / Q000523:psychology*; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002653:Child Behavior Disorders / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D002675:Child, Preschool; D005838:Genotype; D006801:Humans; D007360:Intelligence / Q000145:classification / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory / Q000706:statistics & numerical data; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000502:physiology*; D050638:Receptors, Dopamine D4 / Q000235:genetics* / Q000502:physiology; D020080:Tandem Repeat Sequences / Q000235:genetics; D014888:Wechsler Scales / Q000706:statistics & numerical data
chemical_list: D050638:Receptors, Dopamine D4