Interaction between serotonin transporter promoter and dopamine receptor D4 polymorphisms on decision making

Appropriate decision making is an important brain function to maintain our lives. The Iowa gambling task (IGT) is a tool for decision making under ambiguity. The aims of this study were to evaluate the influence of serotonin transporter linked polymorphic region (5-HTTLPR) and dopamine receptor D4 (DRD4) polymorphisms and their interaction on IGT performance. One hundred fifty-nine normal subjects were involved in this study. All subjects performed the IGT and were genotyped for the triallelic 5-HTTLPR and DRD4 48 bp uVNTR polymorphisms. After controlling for gender, age, and impulsiveness, there were no main effects of 5-HTTLPR and DRD4 gene polymorphisms on total IGT score. However, there was a significant effect on the interaction between 5-HTTLPR and DRD4 on total IGT score. In the presence of the 5-HTTLPR S'S' (SS+SL(G)+L(G)L(G)), subjects with the DRD4 2R+ (2 repeat carrier) had higher total IGT score compared to those with the DRD4 2R-. In contrast, in the absence of the 5-HTTLPR S'S', subjects with the DRD4 2R- had higher total IGT score than those with the DRD4 2R+. When we divided IGT scores into the first and second half of trials, the 5-HTTLPRxDRD4 interaction effects were stronger in the second half block (decision under risk) than in the first half block (decision under ambiguity). In conclusion, the DRD4 genotypes might influence decision-making performance differently according to the background genotypes of 5-HTTLPR.