Multilocus Genetic Profile for Dopamine Signaling Predicts Ventral Striatum Reactivity

• Published in: Neuropsychopharmacology (New York, N.Y.) N.Y.), 2011-08, Vol.36 (9), p.1940-1947
• Main Authors: Nikolova, Yuliya S, Ferrell, Robert E, Manuck, Stephen B, Hariri, Ahmad R
• Format: Article
• Language: English
• Subjects: 631/208/726/649; 631/378/2629/1788; 631/80/86; 692/698/1688/1366/64; Adult; Basal Ganglia - metabolism; Basal Ganglia - physiopathology; Behavioral Sciences; Biological Psychology; Brain research; Cohort Studies; Dopamine; Dopamine - genetics; Dopamine - physiology; Dopamine Plasma Membrane Transport Proteins - genetics; Female; Gene Expression Profiling - methods; Gene loci; Genetic Loci - genetics; Genetic Predisposition to Disease - genetics; Genetics; Humans; Kinases; Male; Medicine; Medicine & Public Health; Middle Aged; Mood Disorders - diagnosis; Mood Disorders - genetics; Mood Disorders - physiopathology; Neurosciences; Original; original-article; Pharmacotherapy; Polymorphism; Polymorphism, Genetic - genetics; Predictive Value of Tests; Psychiatry; Psychopathology; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D4 - genetics; Signal Transduction - genetics
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/npp.2011.82

Research integrating neuroimaging and molecular genetics has yielded important insights into how variability in brain chemistry predicts individual differences in brain function, behavior and related risk for psychopathology. However, existing studies have been limited by their focus on the independent effects of single polymorphisms with modest impact on brain chemistry. Here, we explored the effects of five functional polymorphisms affecting dopamine (DA) signaling on reward-related ventral striatum (VS) reactivity, measured with BOLD fMRI, in a sample of 69 Caucasians. We also compiled individual multilocus genetic profile scores reflecting the additive effects of alleles conferring relatively increased DA signaling across the five polymorphic loci: DAT1 9-repeat, DRD4 7-repeat, DRD2 -141C Del, DRD2 Taq1A C (A2), and COMT 158 Met. These multilocus DA profile scores accounted for 10.9% of the inter-individual variability in reward-related VS reactivity. In contrast, none of the individual polymorphisms accounted for significant variability. Our results show that biologically informed multilocus genetic profiles have unique promise as indices of variability in brain chemistry that may yield advances in mapping individual differences in behaviorally relevant brain function. In turn, such genetic profiles may fuel gene–environment interactions research establishing trajectories of risk for psychopathology.