Brain connectivity and transcriptional changes induced by rTMS in first-episode major depressive disorder

Repetitive transcranial magnetic stimulation (rTMS) is a widely utilized non-invasive brain stimulation technique with demonstrated efficacy in treating major depressive disorder (MDD). However, the mechanisms underlying its therapeutic effects, particularly in modulating neural connectivity and influencing gene expression, remain incompletely understood. In this study, we investigated the voxel-wise degree centrality (DC) induced by 10 Hz rTMS targeting the left dorsolateral prefrontal cortex, as well as their associations with transcriptomic data from the Allen Human Brain Atlas. The results indicated that the active treatment significantly reduced clinical symptoms and increased DC in the left superior medial frontal gyrus, left middle occipital gyrus, and right anterior cingulate cortex. Partial least squares regression analysis revealed that genes associated with DC alternations were enriched biological processes related to neural plasticity and synaptic connectivity. Furthermore, protein-protein interaction (PPI) analysis identified key hub genes, including SCN1A, SNAP25, and PVALB, whose expression levels were positively correlated with DC changes. Notably, SCN1A emerged as a significant predictor on DC changes. These findings suggest that rTMS may exert its therapeutic effects in MDD by modulating specific molecular pathways and neural networks, providing valuable insights into its mechanisms of action.