Major depressive disorder (MDD) is a prevalent chronic mental illness often treated by serotonergic pharmacotherapy and complicated by sex differences and comorbid anxiety disorders (COMs). Deficits in inhibitory control are a transdiagnostic feature of MDD and COM, though the presentation of these deficits may be impacted by competing cognitive demands, symptoms severity, sexes, and medication status.

This project includes 233 participants from the Tulsa 1000 study who completed concurrent electroencephalography (EEG) and magnetic functional resonance imaging (MRI) during a stop signal task (SST). We examined how serotonergic antidepressants, biological sex, and comorbidity with an anxiety disorder uniquely relate to neural indices of inhibitory control for healthy controls (HCs), MDD, and COM using linear mixed effect models, type III ANOVAs, and optimal full propensity matching. N200, P300, and correct-related negativity (CRN) components were extracted and analyzed to index conflict monitoring, conflict resolution, and performance monitoring, respectively, in response to stop signals and their absence.

Our results revealed that HCs exhibited larger stop-P300 amplitudes than MDD and COM (η2 = 0.068); females had smaller stop-N200 amplitudes than males (η2 = 0.027); MDD/COM participants taking a serotonergic antidepressant exhibited less negative N200 amplitudes than those who were not (LME, B = 1.95; η2 = 0.044; ATE, B = 2.47).

Our findings suggest being treated with serotonergic antidepressants are associated with neural differences in the conflict monitoring of inhibitory control in pure and comorbid depression.