The antidepressant mechanism of electroconvulsive therapy (ECT) remains not clearly understood. This study aimed to detect the changes in gray matter volume (GMV) in patients with major depressive disorder (MDD) caused by ECT and exploratorily analyzed the potential functional mechanisms.

A total of 24 patients with MDD who underwent eight ECT sessions were included in the study. Clinical symptom assessments and MRI scans were conducted and compared. Using whole-brain micro-array measurements provided by the Allen Human Brain Atlas (AHBA), regional gene expression profiles were calculated. The differential gene PLS1 was obtained through Partial Least Squares (PLS) regression analysis, and PLS1 was divided into positive contribution (PLS1+) and negative contribution (PLS1−) genes. Through gene function enrichment analysis, the functional pathways and cell types of PLS1 enrichment were identified.

Gray matter volume (GMV) in the somatosensory and motor cortices, occipital cortex, prefrontal cortex, and insula showed an increasing trend after ECT, while GMV in the temporal cortex, posterior cingulate cortex, and orbitofrontal cortex decreased. PLS1 genes were enriched in synapse- and cell-related biological processes and cellular components (such as ‘pre- and post-synapse’, ‘synapse organization’ etc.). A large number of genes in the PLS1+ list were involved in neurons (inhibitory and excitatory), whereas PLS1− genes were significantly involved in Astrocytes (Astro) and Microglia (Micro).

This study established a link between treatment-induced GMV changes and specific functional pathways and cell types, which suggests that ECT may exert its effects through synapse-associated functional and affect neurons and glial cells.