Taq1A polymorphism in the dopamine D2 receptor gene predicts brain metabolic response to aripiprazole in healthy male volunteers

Abstract

Objective The Taq1A polymorphism in the dopamine D2 receptor (DRD2) gene has been reported to be associated with the pharmacodynamics of antipsychotic drugs. We investigated the metabolic response of glucose in the brain to aripiprazole in relation to the DRD2 Taq1A polymorphism. Methods Twenty healthy male volunteers were recruited and were divided into two groups of 10 participants, according to their DRD2 genotypes (A1A1, n=10; A2A2, n=10). The volunteers received single oral doses of aripiprazole (10 mg) and a placebo, following a single-blind, placebo-controlled, randomized, two-way crossover study design. Brain glucose metabolism was assessed using positron emission tomography, scanned with F-18-fluorodeoxyglucose 12 h after the administration of the drug or placebo. Results In voxel-based analysis using SPM2, volunteers with the A2A2 genotype showed decreased metabolism in the right middle frontal gyrus, the left middle and inferior frontal gyrus, the right and left inferior temporal gyrus, and the right cingulate gyrus, and increased metabolism in the pons. In contrast, volunteers with the A1A1 genotype exhibited increased metabolism in the right caudate head, and no brain region showed decreased metabolism. In a region-of-interest analysis, significant interactions between drug and genotype were observed in the right medial orbitofrontal gyrus and the left caudate nucleus. Conclusions This suggests that DRD2 Taq1A polymorphism status may be associated with the clinical response to aripiprazole.