Transcriptional characteristics of human brain alterations in major depressive disorder: A systematic review

Many patients with major depressive disorder (MDD) experience limited treatment effectiveness due to an incomplete understanding of its neurobiological underpinnings. This review integrates neuroimaging and genetic data to examine structural and functional brain changes in MDD, alongside their genetic bases. A PRISMA-guided systematic review of imaging transcriptomics over the past decade was conducted using PubMed and Web of Science. Studies included MRI scans of both MDD patients and healthy controls, as well as brain-wide gene expression data, excluding those that were purely meta-analytical, lacked spatial correlations, or involved transdiagnostic analyses. Of the 206 studies reviewed, 20 met the inclusion criteria. Consistent patterns across studies reveal that key biological processes-such as synaptic signaling, calcium ion binding, neurodevelopment, immune regulation, and neurotransmitter transport-play a central role in brain alterations associated with MDD. Additionally, our findings suggest that electroconvulsive therapy (ECT) may alleviate symptoms by modulating these shared pathways. This review underscores the link between brain changes in MDD and specific gene expression profiles, offering insights that could inform more targeted therapeutic approaches.