Extracellular vesicles in mood disorders: A systematic review of human studies

Extracellular vesicles (EVs) are small, membrane-bound particles that are naturally released by nearly all cell types in the body. They serve as molecular biosignatures, reflecting the state of their cells of origin and providing a non-invasive peripheral marker of central nervous system (CNS) activity under physiological and pathological conditions. We conducted a systematic review (ID: CRD42024528824) of studies investigating the use of EVs in mood disorders within clinical populations. We screened articles indexed in PubMed, EMBASE, Scopus, ISI Web of Science, and APA PsycInfo from January 2010 to October 2024. Available research has focused on four key areas: (1) EV cargo as mechanistic and diagnostic biomarkers; (2) EV cargo as predictive or tracking biomarkers for antidepressant response; (3) EV cargo and neuroimaging correlates; and (4) EV physical properties. Most studies examined major depressive disorder (MDD), with others addressing bipolar disorder (BD), adolescent depression, postpartum depression, and late-life depression. Notably, only 35,55 % of the studies utilized brain-derived EVs. Through analyses of EV-derived miRNA, proteins, mtDNA, and metabolites, these studies have explored neural mitochondrial function, brain insulin resistance, neurogenesis, neuroinflammation, and blood-brain barrier permeability in the context of mood disorders. Some EV-derived markers demonstrated diagnostic and predictive potential. This review discusses key findings, limitations of current research, and future directions for leveraging EVs in the study of mood disorders.