Citation

Kohno M, Nurmi EL, Laughlin CP, Morales AM, Gail EH, Hellemann GS, London ED. Neuropsychopharmacology 2015; 41(3): 695-703.

Affiliation

1] Department of Psychiatry and Biobehavioral Sciences and Semel Institute [2] Department of Molecular and Medical Pharmacology [3] Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Copyright

(Copyright © 2015, Nature Publishing Group)

DOI

10.1038/npp.2015.192

PMID

26119471

Abstract

Brain imaging has revealed links between prefrontal activity during risky decision-making and striatal dopamine receptors. Specifically, striatal dopamine D2-like receptor availability is correlated with risk-taking behavior and sensitivity of prefrontal activation to risk in the Balloon Analogue Risk Task. The extent to which these associations, involving a single neurochemical measure, reflect more general effects of dopaminergic functioning on risky decision-making, however, is unknown. Here, 65 healthy participants provided genotypes and performed the Balloon Analogue Risk Task during functional magnetic resonance imaging. For each participant, dopamine function was assessed using a gene composite score combining known functional variation across five genes involved in dopaminergic signaling: DRD2, DRD3, DRD4, DAT1 and COMT. The gene composite score was negatively related to dorsolateral prefrontal cortical function during risky decision-making, and nonlinearly related to earnings on the task. Iterative permutations of all possible allelic variations (7,777 allelic combinations) was tested on brain function in an independently-defined region of the prefrontal cortex and confirmed empirical validity of the composite score, which yielded stronger association than 95% of all other possible combinations. The gene composite score also accounted for a greater proportion of variability in neural and behavioral measures than the independent effects of each gene variant, indicating that combined effects of functional dopamine pathway genes can provide a robust assessment, presumably reflecting cumulative and potentially interactive effects on brain function. Our findings support the view that the links between dopaminergic signaling, prefrontal function and decision-making vary as a function of dopamine signaling capacity.Neuropsychopharmacology accepted article preview online, 29 June 2015. doi:10.1038/npp.2015.192.

Language: en