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

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Abstract
Externalizing behavior refers to a broad category of behaviors involving disinhibition and approach, including aggression, antisocial behavior, hyperactivity, and impulsivity.1,2 Externalizing behavior problems are typically associated with cognitive impairment, and the negative association between externalizing behavior and IQ is particularly well established.3-7 In attention-deficit/hyperactivity disorder (ADHD), this negative association appears to be primarily genetically based.5 The neuromodulator dopamine has been implicated in various forms of externalizing behavior8-11 and is known to affect cognitive function.12 Localization of the dopamine D4 receptor in the prefrontal cortex13-15 and findings that specific blockade of D4 receptors improves some cognitive impairments16-18 prompted our investigation of the possibility that allelic variation in the dopamine D4 receptor gene (DRD4) might moderate the negative association between externalizing behavior and IQ.