Investigation of the impact of rs3025343 near the dopamine ß-hydroxylase (DBH) gene on reward-related responses within the mesolimbic dopamine system.

OBJECTIVES: Recent research focused on the impact of Neandertal alleles on dopamine-related brain traits. A joint measure of these alleles was reported to be associated with lower dopamine synthesis, presumably leading to reduced activity of the reward system. To isolate single variants, we selected rs3025343 near the dopamine beta hydroxylase gene, which contains a likely introgressed allele. rs3025343 is an established variant for reward system-related psychiatric traits.

METHODS: We hypothesised that the rs3025343 minor allele reduces responses to conditioned reward stimuli in the mesolimbic dopamine system. We tested this hypothesis in a large sample of healthy subjects who underwent fMRI while performing the 'Desire-Reason-Dilemma' paradigm, which allows investigation of reward-related brain responses.

RESULTS: Consistent with our expectation, the rs3025343 minor allele was associated with reduced reward-related activation in core regions of the mesolimbic reward system, i.e. the ventral striatum and the ventral tegmental area, as well as with anteroventral and anterior cingulate regions of the extended reward system.

CONCLUSIONS: These findings provide the first evidence that the likely introgressed minor allele of rs3025343 contributes to a reduced response of the mesolimbic reward system. Further studies in independent samples are needed to replicate these associations and to understand their functional roles.