The accurate perception of facial expressions plays a vital role in daily life, allowing us to select appropriate responses in social situations. Understanding the neuronal basis of altered emotional face processing in patients with major depressive disorder (MDD) may lead to the appropriate choice of individual interventions to help patients maintain social functioning during depressive episodes. Inconsistencies in neuroimaging studies of emotional face processing are caused by heterogeneity in neurovegetative symptoms of depressive subtypes. The aim of this study was to investigate brain activation differences during implicit perception of faces with negative and positive emotions between healthy participants and patients with melancholic subtype of MDD. The neurobiological correlates of sex differences of MDD patients were also examined. Thirty patients diagnosed with MDD and 21 healthy volunteers were studied using fMRI while performing an emotional face perception task. Comparing general face activation irrespective of emotional content, the intensity of BOLD signal was significantly decreased in the left thalamus, right supramarginal gyrus, right and left superior frontal gyrus, right middle frontal gyrus, and left fusiform gyrus in patients with melancholic depression compared to healthy participants. We observed only limited mood-congruence in response to faces of differing emotional valence. Brain activation in the middle temporal gyrus was significantly increased in response to fearful faces in comparison to happy faces in MDD patients. Elevated activation was observed in the right cingulate for happy and fearful faces, in precuneus for happy faces, and left posterior cingulate cortex for all faces in depressed women compared to men. The Inventory for Depressive Symptomatology (IDS) score was inversely correlated with activation in the left subgenual gyrus/left rectal gyrus for sad, neutral, and fearful faces in women in the MDD group. Patients with melancholic features performed similarly to controls during implicit emotional processing but showed reduced activation. This finding suggests that melancholic patients compensate for reduced brain activation when interpreting emotional content in order to perform similarly to controls. Overall, frontal hypoactivation in response to implicit emotional stimuli appeared to be the most robust feature of melancholic depression.
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