Exploring Inflammatory-Related Hub Genes as Therapeutic Targets in Major Depressive Disorder: Implications for Immunological Pathways

This study explored the mechanisms of action of inflammation related central genes in severe depression (MDD) and analyzes their potential as therapeutic targets. By identifying key genes and establishing the link between immune regulatory mechanisms and depression, we provide a theoretical basis for developing more accurate diagnostic and treatment methods. Gene expression datasets related to MDD were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) associated with inflammatory processes were identified and analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Protein-protein interaction (PPI) networks were constructed to identify hub genes. Additionally, we explored regulatory networks of miRNAs, transcription factors, and potential drug interactions were explored. Immune infiltration analysis was performed to examine immune cell profiles. Seven key genes-HMGB1, HSP90AB1, MAPK1, MMP9, MYD88, S100A12, and TLR2-were identified as central players in the inflammatory pathways underlying MDD. These genes demonstrated moderate diagnostic accuracy with AUC values ranging from 0.5 to 0.7. Enrichment analyses revealed significant associations with immune signaling pathways, including IL-17 and Toll-like receptor signaling. Immune infiltration analysis highlighted altered abundances of regulatory T cells, neutrophils, and dendritic cells in MDD samples. Inflammatory-related hub genes play crucial roles in linking immune dysregulation to the pathophysiology MDD pathophysiology. These findings offer insights into the immunological underpinnings of MDD and present potential therapeutic targets for intervention through immune-modulatory approaches.