Relationships between serotonin availability and frontolimbic response to fearful and threatening faces

Serotonin is a critical neurotransmitter in the regulation of emotional behavior. Although emotion processing is known to engage a corticolimbic circuit, including the amygdala and prefrontal cortex, exactly how this brain system is modulated by serotonin remains unclear. Here, we hypothesized that serotonin modulates variability in excitability and functional connectivity within this circuit. We tested whether this modulation contributes to inter-individual differences in emotion processing. Using a multimodal neuroimaging approach with a simultaneous PET-3T fMRI scanner, we simultaneously acquired BOLD signal while participants viewed emotional faces depicting fear and anger, while also measuring serotonin transporter (SERT) levels, regulating serotonin functions. Individuals with higher activity of the medial amygdala BOLD in response to fearful or angry facial expressions, who were temperamentally more anxious, also exhibited lower SERT availability in the dorsal raphe nucleus (DRN). Moreover, higher connectivity of the medial amygdala with the left dorsolateral prefrontal and the anterior cingulate cortex was associated with lower levels of SERT availability in the DRN. These results demonstrate the association between the serotonin transporter level and emotion processing through changes in functional interactions between the amygdala and the prefrontal areas in healthy humans.