In recent studies by our group we accumulated evidence that the effect of certain genetic polymorphisms varies across cognitive processes. The polymorphisms 5-HT1A C(-1019)G (Beste et al., 2011) and TNF-alpha -308G-A (Beste et al., 2011) have been shown to participate in the modulation of cognitive control. For the first time, the present study provides evidence that variations in the GRIN2B gene are associated with decision making.The dopaminergic system is known to modulate decision-making. As N-methyl-d-aspartate (NMDA) receptors strongly influence dopaminergic function, it is conceivable that the glutamatergic system is also involved in decision-making. We examined whether polymorphisms in the N-methyl-d-aspartate receptor 2B subunit gene (GRIN2B) influence decision-making using the Iowa Gambling Task (IGT). In total, 245 (n = 245, 127 female) healthy German students were included in the analysis. Two synonymous SNPs in exon 13, rs1806191 (H1178H) and rs1806201 (T888T) showed the strongest association with aspects of IGT performance. Females with a CC allele in rs1806201 made less use both of a win-stay strategy and demonstrated more exploratory behaviour during task execution. For rs1806191, we found a strong additive effect in usage of a win-stay strategy. This, partly sex-dependent, correlation of the win-stay/lose-shift behaviour with GRIN2B genotypes suggests that healthy individuals with certain GRIN2B variations respond differently to ambiguous conditions, possibly by altered perception of wins and losses. These findings underline the necessity to integrate the glutamatergic system when examining decision-making processes.

Ness, V., Arning, L., Niesert, H.E., Stüttgen, M.C., Epplen, J.T., Beste, C. (2011). Variations in the GRIN2B gene are associated with risky decision-making. Neuropharmacology, 61 (5-6), 950-956.