Multimodal neuroimaging changes and their behavioral, genetic, and neurotransmitter correlates in electroconvulsive therapy for major depressive disorder

Electroconvulsive therapy (ECT) is an effective treatment for major depressive disorder (MDD), yet its underlying mechanisms remain unclear. This study investigated the antidepressant effects of ECT through a multimodal neuro-image meta-analysis combined with functional, genetic, and neurotransmitter assessments. Resting-state functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM) data were analyzed using seed-based d mapping with permutation of subject images (SDM-PSI) to identify changes in brain activation and gray matter volume (GMV) before and after ECT. Further analysis of regions with altered activation and GMV was conducted using Neurosynth, postmortem gene expression data, and receptor/transporter distribution maps to explore molecular underpinnings. The whole-brain multimodal meta-analysis included 291 patients from resting-state fMRI studies and 302 patients from VBM studies. Results showed increased activation and GMV in the left angular gyrus (AG) following ECT. Functional annotation linked the left AG to memory, attention, and perceptual processing. Gene expression analysis identified TFAP2B and OTX2 as the most highly expressed genes in this region. Notably, ECT-induced changes in brain activation and GMV were positively correlated with 5-HT1a receptor and dopamine transporter distribution. These findings suggest the left AG is a key region mediating ECT's effects. Neurotransmitter analysis further indicates that ECT may exert its antidepressant action by modulating neurotransmitter systems, offering insights into the neural and molecular basis of its therapeutic efficacy in MDD.