Dopaminergic genes modulate response inhibition in alcohol abusing adults

• Published in: Addiction biology Vol. 17; no. 6; pp. 1046 - 1056
• Main Authors: Filbey, Francesca M., Claus, Eric D., Morgan, Marilee, Forester, Glen R., Hutchison, Kent
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2012; John Wiley & Sons, Inc
• Subjects: Addiction; Adult; Alcohol use disorders; Alcohol-Related Disorders - genetics; Alcohol-Related Disorders - physiopathology; Alcoholism - genetics; Alcoholism - physiopathology; Alleles; Brain - physiopathology; Computed tomography; Cortex (parietal); Dopamine; Dopamine D2 receptors; Dopamine D4 receptors; Drinking behavior; Drug abuse; Ethanol; Female; fMRI; frontal gyrus; Frontal Lobe - physiopathology; Functional magnetic resonance imaging; Functional Neuroimaging; genes; Genotype; Go/no-go discrimination learning; Go/NoGo; Gyrus Cinguli - physiopathology; Humans; impulsive behavior; Impulsive Behavior - genetics; Impulsive Behavior - physiopathology; Inhibition (Psychology); Magnetic Resonance Imaging; Male; Minisatellite Repeats; Parietal Lobe - physiopathology; Phenotype; Polymorphism, Single Nucleotide; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D4 - genetics; response inhibition
• ISSN: 1355-6215; 1369-1600
• DOI: 10.1111/j.1369-1600.2011.00328.x

ABSTRACT Compulsion in alcohol use disorders (AUD) has been attributed to impairment in response inhibition. Because genes that regulate dopamine (DA) have been implicated not only for risk for AUD but also for impulsivity based on behavioral studies, we set out to examine the underlying neural mechanisms associated with these effects. We collected functional magnetic resonance imaging images on 53 heavy drinking but otherwise healthy adults while performing the Go/NoGo task. We predicted that genetic variants previously reported in the literature to be associated with substance abuse, specifically the DRD2 rs1799732 and DRD4 VNTR, will modulate neural processes underlying response inhibition. Our results showed differential neural response for the DRD4 VNTR during successful inhibition in the inferior frontal gyrus (IFG) (cluster‐corrected P < 0.05, z = 1.9). Similarly, DRD2 rs1799732 groups were significantly different in the precuneus and cingulate gyrus during successful response inhibition (cluster‐corrected P < 0.05, z = 1.9). These findings provide further evidence for the role of DAergic genes in modulating neural response in areas that underlie response inhibition and self‐monitoring processes. Variants within these genes appear to influence processes related to impulsive behavior, which may increase one's risk for alcohol abuse and dependence.