Dissociable Neural Responses to Monetary and Social Gain and Loss in Women With Major Depressive Disorder

Neuroimaging studies have revealed aberrant reward and loss processing in patients with major depressive disorder (MDD). While most studies use monetary stimuli to study these processes, it is important to consider social stimuli given that the social environment plays a significant role in the development and maintenance of MDD. In the present study, we examined whether monetary gain/loss and social acceptance/rejection would elicit dissociable salience-related neural responses in women diagnosed with MDD compared to healthy control (HC) women. Twenty women diagnosed with MDD and 20 matched HC women performed the monetary incentive delay task (MID) and the social feedback task (SFT) during functional magnetic resonance imaging (fMRI). This study focused on women since women have a higher rate of MDD, higher frequency of relapse, and are more likely to develop MDD as a consequence of negative interpersonal relationships compared to men. We found that during the MID, HCs but not MDD patients demonstrated strong overlapping activations in the right anterior insula (AI) in response to both monetary gain and loss. During the SFT, MDD patients but not HCs showed overlapping activations in the AI in response to social acceptance and rejection. Our results may suggest a dissociation such that MDD patients show decreased sensitivity to monetary stimuli whether gain or loss, and increased sensitivity to social stimuli whether acceptance or rejection, although this will need to be verified in larger samples with direct comparisons between groups and stimuli. These data demonstrate distinct abnormalities in reward and loss processing that converge within the AI. Our findings also highlight the critical need to assess across both non-social and social domains when examining reward and loss systems in MDD to broaden our understanding of the disorder and identify novel targets for treatment.