Plasma-Derived Small Extracellular Vesicles miR- 182 - 5p Is a Potential Biomarker for Diagnosing Major Depressive Disorder

Depression, particularly major depressive disorder (MDD), is a debilitating neuropsychiatric condition characterized by high disability rates, primarily driven by chronic stress and genetic predispositions. Emerging evidence highlights the critical role of microRNAs (miRNAs) in the pathogenesis of depression, with plasma-derived small extracellular vesicles (sEVs) emerging as promising biomarkers. In this study, we collected peripheral blood plasma samples from patients diagnosed with MDD, as assessed by the Hamilton Depression Rating scale, alongside healthy individuals serving as controls. Plasma-derived sEVs were isolated via ultracentrifugation, followed by high-throughput sequencing of miRNAs encapsulated within sEVs, and finally image acquisition and differential expression analysis. Our results revealed a significant elevation of miR-182-5p in plasma-derived sEVs from MDD patients compared to healthy controls, a finding further validated in chronic mild stress (CMS) models. Further analysis suggested that miRNAs encapsulated within sEVs may influence depression onset and progression by modulating hypothalamic-pituitary-adrenal (HPA) axis activity. These findings underscore the potential of miRNAs and their target genes as novel biomarkers, offering improved diagnostic accuracy and therapeutic efficacy for MDD.