Abstract/Summary

Background: Patients on the selective serotonergic re-uptake inhibitors (SSRI) like citalopram report emotional blunting. We have shown previously that citalopram reduces resting-state functional connectivity (RSFC) in healthy volunteers in a number of brain regions including the dorso-medial prefrontal cortex, which may be related to its clinical effects. Bupropion is a dopaminergic and noradrenergic re-uptake inhibitor (DNRI) and is not reported to cause emotional blunting. However how bupropion affects RSFC in healthy controls remains unknown. Methods: Using a within subjects, repeated measures, double-blind, cross-over design we examined 17 healthy volunteers (9 female, 8 male). Volunteers received 7 days of bupropion (150 mg/day) and 7 days of placebo treatment and underwent resting-state functional Magnetic Resonance Imaging. We selected seed regions in the salience network (SN: amygdala and pregenual anterior cingulate cortex (pgACC)) and the central executive network (CEN: dorsal medial prefrontal cortex (dmPFC)). Mood and anhedonia measures were also recorded and examined in relation to RSFC. Results: Relative to placebo, bupropion increased RSFC in healthy volunteers between the dmPFC seed region and the posterior cingulate cortex and the precuneus cortex, key parts of the default mode network. Conclusions: These results are opposite to that which we found with 7 days treatment of citalopram in healthy volunteers. These results reflect a different mechanism of action of bupropion compared to SSRIs. These results help explain the apparent lack of emotional blunting caused by bupropion in depressed patients.