Neuronal response to high negative affective stimuli in major depressive disorder: An fMRI study

Background: Disturbed emotion processing underlies depression. We examined the neuronal underpinnings of emotional processing in patients (PAT) with major depressive disorder (MDD) compared to healthy volunteers (HV) using functional magnetic resonance (fMRI) scan. Methods: Thirty-six MDD patients and 30 HV underwent T2-weighted fMRI assessments during the presentation of an implicit affective processing task in three conditions. They differed regarding their affective quality (=valence, high negative, low negative and neutral stimuli) and regarding the arousal based on stimuli from the International Affective Picture System. Results: Group contrasts showed lower left-sided activation in dorsolateral prefrontal cortex (DLPFC), anterior PFC, precentral and premotor cortex in PAT compared with HV (Cluster-level threshold, 5000 iterations, p<0.01). We found a significant interaction effect of valence and group, a significant effect of emotional valence and a significant effect of group. All effects were shown in brain regions within the emotional network (Cluster-level threshold, 5000 iterations, p<0.01). Higher arousal (rho=-0.33, p<0.01) and higher valence (rho=-0.33, p<0.01) during high negative stimuli presentation as well as more severe depression (Beck Depression Inventory II [BDI II]; r = 0.39, p = 0.01) were significantly negatively associated with left DLFPC activity in patients. Limitations: Potential influence of psychopharmacological drugs on functional activation is one of the most discussed source of bias in studies with medicated psychiatric patients. Conclusions: The results highlight the importance of left DLPFC during the processing of negative emotional stimuli in MDD. The integration of a neurophysiological model of emotional processing in MDD may help to clarify and improve therapeutic options.