Persistence of amygdala hyperactivity to subliminal negative emotion processing in the long-term course of depression

Biased emotion processing has been suggested to underlie the etiology and maintenance of depression. Neuroimaging studies have shown mood-congruent alterations in amygdala activity in patients with acute depression, even during early, automatic stages of emotion processing. However, due to a lack of prospective studies over periods longer than 8 weeks, it is unclear whether these neurofunctional abnormalities represent a persistent correlate of depression even in remission. In this prospective case-control study, we aimed to examine brain functional correlates of automatic emotion processing in the long-term course of depression. In a naturalistic design, n = 57 patients with acute major depressive disorder (MDD) and n = 37 healthy controls (HC) were assessed with functional magnetic resonance imaging (fMRI) at baseline and after 2 years. Patients were divided into two subgroups according to their course of illness during the study period (n = 37 relapse, n = 20 no-relapse). During fMRI, participants underwent an affective priming task that assessed emotion processing of subliminally presented sad and happy compared to neutral face stimuli. A group × time × condition (3 × 2 × 2) ANOVA was performed for the amygdala as region-of-interest (ROI). At baseline, there was a significant group × condition interaction, resulting from amygdala hyperactivity to sad primes in patients with MDD compared to HC, whereas no difference between groups emerged for happy primes. In both patient subgroups, amygdala hyperactivity to sad primes persisted after 2 years, regardless of relapse or remission at follow-up. The results suggest that amygdala hyperactivity during automatic processing of negative stimuli persists during remission and represents a trait rather than a state marker of depression. Enduring neurofunctional abnormalities may reflect a consequence of or a vulnerability to depression.