Genome-wide transcriptomic and biochemical profiling of major depressive disorder: Unravelling association with susceptibility, severity, and antidepressant response

Identifying biomarkers for diagnosing Major Depressive Disorder (MDD), assessing its severity, and guiding treatment is crucial. We conducted whole genome transcriptomic study in North Indian population, and analyzed biochemical parameters. Our longitudinal study investigated gene-expression profiles from 72 drug-free MDD patients and 50 healthy controls(HCs) at baseline and 24 patients after 12-weeks of treatment. Gene expression analyses identified differentially expressed genes(DEGs) associated with MDD susceptibility, symptom severity and treatment response, independently validated by qPCR. Hierarchical clustering revealed distinct expression patterns between MDD and HCs, also between mild and severe cases. Enrichment analyses of significant DEGs revealed inflammatory, apoptosis, and immune-related pathways in MDD susceptibility, severity, and treatment response. Simultaneously, we assessed thirty biochemical parameters in the same cohort, showed significant differences between MDD and HCs in 13 parameters with monocytes, eosinophils, creatinine, SGPT, and total protein remained independent predictors of MDD in a multivariate-regression model. Our study supports the role of altered immune/inflammatory signaling in MDD pathophysiology, offering clinically relevant biochemical parameters and insights into transcriptomic gene regulation in MDD pathogenesis and treatment response.