Neurobiological mechanisms of electroconvulsive therapy in major depressive disorder: structure-function coupling with gene expression and molecular mechanism

作者：Rui Qian, Wanling Huang, Yang Ji, Shuang Zheng, Jun Huang, Hao Zheng, Jie Hu, Rui Li, Chenchen Zhang, Yue Yu, Kun Li, Yanghua Tian, Kai Wang · 发表于：Translational Psychiatry · 年份：2026 · DOI：10.1038/s41398-026-03892-z · 被引用次数：2 · 研究领域：Electroconvulsive Therapy Studies、Treatment of Major Depression、Functional Brain Connectivity Studies

Major Depressive Disorder (MDD), a common and debilitating mental disorder, contributes considerably to global disease burden by increasing rates of comorbid physical illnesses, functional impairment, and suicide risk. Despite a spectrum of therapeutic modalities, a significant proportion of patients, particularly those with treatment-resistant depression, fail to achieve adequate symptom remission. Electroconvulsive Therapy (ECT) remains a pivotal intervention for refractory cases and is characterized by its rapid antidepressant efficacy; however, the underlying neurobiological mechanisms remain insufficiently elucidated. In this investigation, longitudinal neuroimaging of 88 MDD patients revealed that ECT decisively modulated structural-functional connectivity (SC-FC) coupling within the default mode network (DMN) and somatomotor network (SMN), suggesting reintegration of large-scale neural circuits. Notably, baseline SC-FC metrics incorporated into support vector regression (SVR) model reliably predicted symptomatic amelioration following ECT, while network-based spreading analysis delineated probable loci of therapeutic impact. At the molecular level, ECT enhanced mitochondrial respiration, reconfigured neuroplasticity-related pathways, and modulated gene expression underlying SC-FC coupling, alongside profound effects on serotonergic and dopaminergic neurotransmission. By converging neuroimaging and transcriptomic evidence, this study elucidates the multifaceted neurobio...