ORIGINAL ARTICLE The Dopamine D4 Receptor Gene and Moderation of the Association Between Externalizing Behavior and IQ

plicated in externalizing behavior problems, such as ag-gression and hyperactivity. Externalizing behavior is known to be negatively associated with cognitive abil-ity. Activation of dopamine D4 receptors appears to in-hibit the functioning of the prefrontal cortex, a brain re-gion implicated in cognitive ability. The 7-repeat allele of the dopamine D4 receptor gene produces less effi-cient receptors, relative to other alleles, and this may al-ter the effects of dopamine on cognitive function. Objective: To examine the influence of a polymor-phism in the third exon of the dopamine D4 receptor gene on the association between externalizing behavior and IQ. Design: In 1 community sample and 2 clinical samples, the presence or absence of the 7-repeat allele was exam-ined as a moderator of the association between external-izing behavior and IQ; the strength of this effect across samples was estimated meta-analytically. Patients: Eighty-seven boys from a longitudinal com-munity study, 48 boys referred clinically for aggression, and 42 adult males diagnosed with attention-deficit/ hyperactivity disorder. MainOutcomeMeasures: IQ scores and observer rat-ings 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 behav-ior 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 re-ceptor gene appears to be a genetic factor moderating the association between externalizing behavior and cogni-tive ability. This finding may help to elucidate the adap-tive value of the 7-repeat allele