Effects of serotonin and dopamine depletion on neural prediction computations during social learning

We have previously shown that individuals with high depression scores demonstrate impaired behavioral and neural responses during social learning. Given that depression is associated with altered dopamine (DA) and serotonin (5-HT) functioning, the current study aimed to elucidate the role of these neurotransmitters in the social learning process using a dietary depletion manipulation. In a double-blind design, 70 healthy volunteers were randomly allocated to a 5-HT depletion (N = 24), DA depletion (N = 24), or placebo (N = 22) group. Participants performed a social learning task during fMRI scanning, as part of which they learned associations between name cues and rewarding (happy faces) or aversive (fearful faces) social outcomes. Behaviorally, 5-HT depleted subjects demonstrated impaired social reward learning compared to placebo controls, with a marginal effect in the same direction in the DA depletion group. On the neural level, computational modeling-based fMRI analyses revealed that 5-HT depletion altered social reward prediction signals in the insula, temporal lobe, and prefrontal cortex, while DA depletion affected social reward prediction encoding only in the prefrontal cortex. These results indicate that 5-HT depletion impairs learning from social rewards, on both the behavioral and the neural level, while DA depletion has a less extensive effect. Interestingly, the behavioral and neural responses observed after 5-HT depletion in the current study closely resemble our previous findings in individuals with high depression scores using the same task. It may thus be the case that decreased 5-HT levels contribute to social learning deficits in depression.