Clinical studies of blood-borne Extracellular vesicles in psychiatry: A systematic review

Biomarkers for the diagnosis and clinical management of psychiatric disorders are currently lacking. Extracellular vesicles (EVs), lipid membrane-encapsulated vesicles released by cells, hold promise as a source of biomarkers due to their ability to carry molecules that reflect the status of their donor cells and their ubiquitous presence in biofluids. This review examines the literature on EVs in biofluids from psychiatric disorder patients, and discuss how the published studies contribute to our understanding of the pathophysiology of these conditions and to the discovery of potential biomarkers. We analyzed 46 studies on blood-borne EVs; no investigations on cerebrospinal fluid-derived EVs were found. A significant number of studies lacked optimal description of the methodology and/or characterization of the isolated EVs. Moreover, many studies aimed to capture brain-derived EVs, but often capture-proteins with low brain specificity were used. Considering biomarkers, miRNAs were the most investigated molecular type, but based on the studies analyzed it was not possible to identify robust biomarker candidates for the investigated disorders. Additionally, we describe the contribution of EV studies in illuminating the pathophysiology of psychiatric disorders, including research on insulin resistance, inflammation, mitochondrial dysfunction, and the microbiota. We conclude that there is a shortage of studies with detailed methodology description and EV sample characterization in psychiatric research. To exploit the potential of EVs to investigate psychiatric disorders and identify biomarkers more studies and validated protocols using capture proteins with high specificity to brain cells are needed. The review protocol was pre-registered in the PROSPERO database under the registration number CRD42021277534.