Neural correlates of social processing in major depressive disorder: A coordinate-based Meta-analysis of task-related...

Social processing deficits are prevalent in major depressive disorder (MDD); however, the exact mechanisms responsible for these deficits are uncertain. This study conducts a coordinate-based meta-analysis of functional magnetic resonance imaging (fMRI) studies to elucidate neural dysfunctions during social processing tasks in MDD.

We conducted a systematic literature search on Web of Science, PubMed, and Embase following the PRISMA guidelines. A voxel-wise meta-analysis was performed using the SDM software, focusing on the social process as defined by the Research Domain Criteria (RDoC).

Fifteen studies comprising 342 MDD patients and 397 healthy controls were included in our meta-analysis, revealing distinct neural patterns during social processing in depression. Compared to controls, MDD patients showed higher activation in self-referential networks (right angular gyrus, bilateral superior/middle frontal gyri) and cerebellar regions (lobule VI), alongside decreased activation in social-perceptual areas (bilateral fusiform gyri, right insula/inferior occipital cortex). Notably, symptom severity negatively correlated with activity in cerebellar lobule VI (BA 37) and angular gyrus (BA 39), while female participants exhibited increased recruitment of prefrontal and callosal regions.

Our findings reveal a potential "social processing circuit dysfunction" in MDD, characterized by hyperactivity in self-referential processing regions (DMN) coupled with hypoactivity in social perception areas. Both cerebellar and angular gyrus activities independently correlate negatively with depression severity further implying that this circuit dysfunction may be a neural correlate of clinical severity. These aberrations have significant implications for improving social functioning and overall quality of life in those with MDD.