Similar Improvement of Reward and Punishment Learning by Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder

Background: The role of dopamine in reinforcement learning has been extensively studied, but the role of other major neuromodulators, particularly serotonin, remains poorly understood. An influential theory has suggested that dopamine and serotonin represent opponent systems respectively driving reward and punishment learning. Methods: To test this theory, we compared two groups of patients with obsessive-compulsive disorder, one unmedicated (n = 12) and one treated with serotonin reuptake inhibitors (SRI; n = 13). To avoid confounding basic reinforcement learning with strategic conscious reasoning, we used a subliminal conditioning task that involves subjects learning to associate masked cues with gambling outcomes to maximize their payoff. The same task was used in a previous study to demonstrate opposite effects of dopaminergic medication on reward and punishment learning. Results: Unmedicated obsessive-compulsive disorder patients exhibited an instrumental learning deficit that was fully alleviated under SRI treatment. Contrary to dopaminergic medication, SRIs similarly modulated reward and punishment learning. Conclusions: Thus, departing from the opponency model, our results support a beneficial role of serotonin in instrumental learning that is independent of outcome valence.