This study aims to investigate gene expression changes in different brain regions of Major Depressive Disorder (MDD) patients using transcriptomics and bioinformatics approaches. Through differential expression gene (DEG) analysis, functional enrichment analysis, and Weighted Gene Co-expression Network Analysis (WGCNA), we aimed to identify key genes, pathways, and co-expression modules associated with MDD, with particular emphasis on the role of neuroinflammation and endoplasmic reticulum (ER) stress pathways in MDD pathology and their region-specific characteristics. The findings of this study will provide novel insights into the complex molecular mechanisms of MDD and lay the foundation for the future development of diagnostic biomarkers and therapeutic targets.