The role of 5-HTTLPR in choosing the lesser of two evils, the better of two goods: examining the impact of 5-HTTLPR genotype and tryptophan depletion in object choice

Rationale The serotonin (5-HT) system is considered important for decision-making. However, its role in reward- and punishment-based processing has not yet been clearly determined. Objectives The present study examines the effect of 5-HTTLPR genotype and tryptophan depletion on reward- and punishment-related processing, using a task that considers decision-making in situations of subtlety of choice. Thus, it considers that response choice often occurs in situations where both options are desirable (e.g., choosing between mousse au chocolat or creme caramel cheesecake from a menu) or undesirable. It also considers that response choice is easier when the reinforcements associated with the options are far apart, rather than close, in value. Materials and methods Healthy volunteers underwent acute tryptophan depletion (ATD) or control procedures and genotyping of the 5-HTTLPR for long and short allele variants. We then examined the effects and interactions of ATD and the serotonin promoter polymorphism genotype on two aspects of decision-making: (a) decision form, choosing between two objects to gain the greater reward or lesser punishment and (b) between-object reinforcement distance, the difference in reinforcements associated with two options. Results ATD and LL homozygosity had comparable interactions with decision form and between-object reinforcement distance. Specifically, both modulated the effect of between-object reinforcement distance when deciding between objects both associated with punishment. Moreover, ATD and genotype interacted with ATD disproportionately affecting the performance of the LL homozygous group. Conclusions These results suggest that serotonin is particularly associated with punishment, rather than reward-related processing, and that individual sensitivity to punishment-related information and tryptophan depletion varies with genotype.