Abstract：
Although previous studies reported structural changes associated with electroconvulsive therapy (ECT) in major depressive disorder (MDD), the underlying molecular basis of ECT remains largely unknown. Here, we combined two independent structural MRI datasets of MDD patients receiving ECT and transcriptomic gene expression data from Allen Human Brain Atlas to reveal the molecular basis of ECT for MDD. We performed partial least square regression to explore whether/how gray matter volume (GMV) alterations were associated with gene expression level. Functional enrichment analysis was conducted using Metascape to explore ontological pathways of the associated genes. Finally, these genes were further assigned to seven cell types to determine which cell types contribute most to the structural changes in MDD patients after ECT. We found significantly increased GMV in bilateral hippocampus in MDD patients after ECT. Transcriptome-neuroimaging association analyses showed that expression levels of 726 genes were positively correlated with the increased GMV in MDD after ECT. These genes were mainly involved in synaptic signaling, calcium ion binding and cell-cell signaling, and mostly belonged to excitatory and inhibitory neurons. Moreover, we found that the MDD risk genes of CNR1, HTR1A, MAOA, PDE1A, and SST as well as ECT related genes of BDNF, DRD2, APOE, P2RX7, and TBC1D14 showed significantly positive associations with increased GMV. Overall, our findings provide biological and molecular mechanisms underlying structural plasticity induced by ECT in MDD and the identified genes may facilitate future therapy for MDD.
摘要：
尽管先前的研究报道了重度抑郁症（MDD）的电惊厥治疗（ECT）相关的结构变化，ECT的潜在分子基础在很大程度上仍然未知。这里,我们将接受ECT的MDD患者的两个独立的结构MRI数据集和来自Allen人脑图谱的转录组基因表达数据结合起来,以揭示ECT治疗MDD的分子基础.我们进行了偏最小二乘回归以探索灰质体积（GMV）改变是否/如何与基因表达水平相关。使用Metascape进行功能富集分析以探索相关基因的本体途径。最后,这些基因被进一步分配到7种细胞类型,以确定哪些细胞类型对ECT后MDD患者的结构变化贡献最大.我们发现ECT后MDD患者双侧海马GMV明显增加。转录组-神经影像学关联分析显示，726个基因的表达水平与ECT后MDD中GMV的增加呈正相关。这些基因主要参与突触信号,钙离子结合和细胞-细胞信号，主要属于兴奋性和抑制性神经元。此外，我们发现CNR1、HTR1A、MAOA,PDE1A,和SST以及BDNF的ECT相关基因，DRD2，APOE，P2RX7和TBC1D14显示与GMV增加的显著正相关。总的来说,我们的发现提供了ECT在MDD中诱导结构可塑性的生物学和分子机制,鉴定的基因可能有助于MDD的未来治疗.
