Serotonin Transporter Genetic Variation is Differentially Associated with Reflexive- and Reflective-Optimal Learning.

Learning to respond optimally under a broad array of environmental conditions is a critical brain function that requires engaging the cognitive systems that are optimal for solving the task at hand. Serotonin is implicated in learning and decision-making, but the specific functions of serotonin in system-level cognitive control remain unclear. Across 3 studies, we examined the influence of a polymorphism within the promoter region of the serotonin transporter gene (5-HTTLPR polymorphism in SLC6A4) on participants' ability to engage the task appropriate cognitive system when the reflexive (Experiments 1 and 2) or the reflective (Experiment 3) system was optimal. Critically, we utilized a learning task for which all aspects remain fixed with only the nature of the optimal cognitive processing system varying across experiments. Using large community samples, Experiments 1 and 2 (screened for psychiatric diagnosis) found that 5-HTTLPR S/LG allele homozygotes, with putatively lower serotonin transport functionality, outperformed LA allele homozygotes in a reflexive-optimal learning task. Experiment 3 used a large community sample, also screened for psychiatric diagnosis, and found that 5-HTTLPR LA homozygotes, with putatively higher serotonin transport functionality, outperformed S/LG allele homozygotes in a reflective-optimal learning task.