Double dissociation between lab measures of inattention and impulsivity and the dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4).

Studies examining the biological and neuropsychological processes underlying attention-deficit/hyperactivity disorder (ADHD) suggest that error indices from the A-X Continuous Performance Test (A-X CPT) might represent useful endophenotypes for ADHD. The current study extended such findings by evaluating the utility of these putative endophenotypes in the context of a molecular genetic study. One hundred and forty-eight clinic-referred ADHD probands and 56 siblings were recruited as part of an ongoing study. Between- and within-family tests of association were conducted to test for relations between polymorphisms in two candidate genes, the dopamine transporter gene (DAT1) and the dopamine D4 receptor gene (DRD4), and indices of inattention and impulsivity derived from the A-X CPT. Association analyses of these polymorphisms with the A-X CPT indices suggested a double dissociation such that an index of inattention was associated with DRD4 but not DAT1, and an index of impulsivity was associated with DAT1 but not DRD4. Further analyses suggested that an A-X CPT index of impulsivity partially mediated previously observed associations between hyperactive-impulsive ADHD symptoms and DAT1. Additionally, an A-X CPT index of inattention moderated the relation between inattentive ADHD symptoms and DRD4 such that children with high levels of the endophenotype showed a stronger association between inattentive symptoms and DRD4. The potential utility of endophenotypes derived from the A-X CPT in molecular genetic studies of ADHD is discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved).