Small Extracellular Vesicles in Mood Disorders: Mapping the Evidence for Glia-Marker-Enriched Fractions as Candidate Mediators of Brain–Body Communication—A Narrative Review

Background: Mood disorders are associated with excess mortality and with cardiovascular, oncological, endocrine and gastrointestinal disease, yet the mechanisms that link the brain and the body remain unclear. Small extracellular vesicles (sEVs) cross the blood–brain barrier and carry protein, lipid and RNA cargo, and cell-type-specific enrichment makes it possible, in principle, to interrogate astrocyte-, microglia- and neuron-associated populations in peripheral blood. Objective: To map what is currently known about glia-associated sEVs in mood disorders and to relate their cargo to the somatic conditions that accompany these disorders. Methods: PubMed and Scopus were searched for the period 2014–2026 (last accessed 21 August 2026) with four queries on the role of exosomes and extracellular vesicles in depression and bipolar disorder. Results: Sixty-six human studies were included. Operationally defined cell-marker-enriched fractions were classified as astrocyte-related (6), microglia-related (1), neuron-related (14), bacteria-related (1), and unfractionated/total (44); no study examined oligodendrocyte-related vesicles. Only seven studies addressed glia-related fractions, and one was an iPSC model. Glia-related fractions carried cytokine, neurotrophic, vitamin D-binding protein and VEGF signals that did not mirror corresponding serum concentrations. However, these findings are associative and depend on immunocapture protocols of unproven specificity. Conclusions: Glia-associated sEVs are a plausible but still sparsely tested route of brain–body communication in mood disorders; causal evidence is lacking. Progress requires validated cell-of-origin markers, MISEV-compliant reporting, longitudinal designs, and functional validation in cellular/animal models.