BACKGROUND: Major depressive disorder (MDD) is a prevalent neuropsychiatric illness for which it is important to resolve underlying brain mechanisms. Current treatments are often unsuccessful, precipitating a need to identify predictive markers.

AIM: We evaluated (1) alterations in brain responses to an emotional faces functional magnetic resonance imaging (fMRI) paradigm in individuals with MDD, compared to controls, (2) whether pretreatment brain responses predicted antidepressant treatment response, and (3) pre-post change in brain responses following treatment.

METHODS: Eighty-nine medication-free, depressed individuals and 115 healthy controls completed the fMRI paradigm. Depressed individuals completed a nonrandomized, open-label, 8-week treatment with escitalopram, including the option to switch to duloxetine after 4 weeks. We examined patient-control group differences in regional fMRI responses at baseline, whether baseline fMRI responses predicted treatment response at 8 weeks, including early life stress moderating effects, and change in fMRI responses in 36 depressed individuals rescanned following 8 weeks of treatment.

RESULTS: Task reaction time was 5% slower in patients. Multiple brain regions showed significant task-related responses, but we observed no statistically significant patient-control group differences (Cohen's d  < 0.35). Patient pretreatment brain responses did not predict antidepressant treatment response (area under the curve of the receiver operator characteristic (AUC-ROC) < 0.6) and brain responses were not statistically significantly changed after treatment (Cohen's d  < 0.33).

CONCLUSION: This represents the largest prediction study to date examining emotional faces fMRI features as predictors of antidepressant treatment response. Brain response to this fMRI emotional faces paradigm did not distinguish depressed individuals from healthy controls, nor was it predictive of antidepressant treatment response. Clinical Trial Registration: Site: https://clinicaltrials.gov, Trial Number: NCT02869035, Trial Title: Treatment Outcome in Major Depressive Disorder.