Mood-Linked Responses in Medial Prefrontal Cortex Predict Relapse in Patients with Recurrent Unipolar Depression

Background: Altered cognitive processing following mood challenge is associated with elevated relapse risk in remitted unipolar depressed patients, but little is known about the neural basis of this reactivity and its link to depressive relapse and prophylaxis. Methods: Remitted unipolar depressed participants (n = 16) and healthy control subjects (n = 16) underwent functional magnetic resonance imaging (fMRI) while viewing sad and neutral film clips. Correlations were determined between emotional reactivity (neural responses to sad vs. neutral films) in remitted patients and subsequent relapse status over an 18 month follow-up period. A receiver operating characteristic analysis was used to determine signal cutoffs for predicting relapse. Emotional reactivity in relapse prognostic areas was compared between groups. Results: Within the remitted group, relapse was predicted by medial prefrontal cortical (mPFC; Brodmann's area 32) activity and contraindicated by visual cortical activity (Brodmann's area 17). mPFC reactivity predicted rumination, whereas visual cortical reactivity predicted distress tolerance (acceptance). Compared with control participants, remitted depressed patients demonstrated a more pronounced tradeoff between mPFC and visual cortex reactivity. The difference score between mPFC and visual reactivity yielded excellent prediction of depressive relapse. Conclusions: Medial prefrontal cortical reactivity to mood provocation in remitted unipolar depressed patients serves as a marker of relapse risk rather than successful emotion regulation. Enduring remission is characterized by normalization of the mPFC to that of healthy control subjects. Furthermore, visual cortex reactivity predicts resilience against depressive relapse, indicating a prophylactic role for sensory rather than ruminative cognitive reactivity in the processing of negative emotion.