Gray matter abnormalities in patients with major depressive disorder and social anxiety disorder: a voxel-based meta-analysis

Background: Major depressive and social anxiety disorders have a high comorbidity rate and similar cognitive patterns. However, their unique and shared neuroanatomical characteristics have not been fully identified.

Methods: Voxel-based morphometric studies comparing gray matter volume between patients with major depressive disorder/social anxiety disorder and healthy controls were searched using 4 electronic databases from the inception to March 2022. Stereotactic data were extracted and subsequently tested for convergence and differences using activation likelihood estimation. In addition, based on the result of the meta-analysis, behavioral analysis was performed to assess the functional roles of the regions affected by major depressive disorder and/or social anxiety disorder.

Results: In total, 34 studies on major depressive disorder with 2873 participants, and 10 studies on social anxiety disorder with 1004 subjects were included. Gray matter volume conjunction analysis showed that the right parahippocampal gyrus region, especially the amygdala, was smaller in patients compared to healthy controls. The contrast analysis of major depressive disorder and social anxiety disorder revealed lower gray matter volume in the right lentiform nucleus and medial frontal gyrus in social anxiety disorder and lower gray matter volume in the left parahippocampal gyrus in major depressive disorder. Behavioral analysis showed that regions with lower gray matter volume in social anxiety disorder are strongly associated with negative emotional processes.

Conclusions: The shared and unique patterns of gray matter volume abnormalities in patients with major depressive and social anxiety disorder may be linked to the underlying neuropathogenesis of these mental illnesses and provide potential biomarkers. PROSPERO registration number: CRD42021277546.