Extracellular Vesicles in Psychiatry Research in the Context of RDoC Criteria

Abstract

The analysis of extracellular vesicles has been accelerated because of the technological advancements in omics methods in recent decades. Extracellular vesicles provide multifaceted information regarding the functional status of the cells. This information would be critical in case of central nervous system cells, which are confined in a relatively sealed biological compartment. This obstacle is more dramatic in psychiatric disorders since their diagnosis primarily depend on the symptoms and signs of the patients. In this paper, we reviewed this rapidly advancing field by discussing definition of extracellular vesicles, their biogenesis and potential use as clinical biomarkers. Then we focused on their potential use in psychiatric disorders in the context of diagnosis and treatment of these disorders. Finally, we tried to combine the RDoC (Research Domain Criteria) with the use of extracellular vesicles in psychiatry research and practice. This review may offer new insights in both basic and translational research focusing on psychiatric disorders.

Molecular and Cellular Impact of Inflammatory Extracellular Vesicles (EVs) Derived from M1 and M2 Macrophages on Neural Action Potentials

“…Extracellular vesicles (EVs) are potent vehicles of intracellular signaling, and cells transfer information through the secretion of these vesicles [36]. Extracellular vesicles have been isolated from bodily fluids, and they have a key role in both the regulation of normal physiological processes and the pathology underlying several diseases [37].…”

Circulating Extracellular Vesicles: The Missing Link between Physical Exercise and Depression Management?

“…Evidence for such an argument was readily supported by other authors over the last couple of years [ 49 , 51 , 52 , 62 , 74 ]. Excitingly, the emerging potential of circulating EVs in the pathogenesis, diagnosis and treatment of psychiatric disorders, including depression, sparked our interest [ 44 , 45 , 46 ]. EVs are known to cross the blood–brain barrier (BBB) and, thus, may provide a relatively non-invasive way to obtain information from the brain (peptides or miRNA biomarkers) and may function as delivery vehicles to target brain dysfunction [ 44 , 46 ].…”

“…Excitingly, the emerging potential of circulating EVs in the pathogenesis, diagnosis and treatment of psychiatric disorders, including depression, sparked our interest [ 44 , 45 , 46 ]. EVs are known to cross the blood–brain barrier (BBB) and, thus, may provide a relatively non-invasive way to obtain information from the brain (peptides or miRNA biomarkers) and may function as delivery vehicles to target brain dysfunction [ 44 , 46 ]. Although there is some evidence regarding circulating proteins [ 75 ] or miRNAs [ 44 ] as putative biomarkers for depression, scientific studies on the effects of PE-associated circulating EVs on either depression onset, progression or amelioration are still missing.…”

“…Blood is an excitingly non-invasive alternative to capture EVs from the brain, which may be a promising platform for “liquid biopsies” in neurodegenerative or psychiatric disorders, namely depression. In fact, the lack of an accurate diagnosis represents a major obstacle to effective depression management [ 44 , 45 , 46 ]. Circulating biomarkers may reflect the pathological changes in the central nervous system (CNS), enabling more accurate depression diagnosis and stratification [ 47 , 48 ] and unveiling exciting perspectives for the monitoring of the effectiveness of PE in depression [ 27 , 46 , 49 ].…”

“…In fact, the lack of an accurate diagnosis represents a major obstacle to effective depression management [ 44 , 45 , 46 ]. Circulating biomarkers may reflect the pathological changes in the central nervous system (CNS), enabling more accurate depression diagnosis and stratification [ 47 , 48 ] and unveiling exciting perspectives for the monitoring of the effectiveness of PE in depression [ 27 , 46 , 49 ]. Indeed, blood EV concentrations and cargo signatures (proteins, RNAs, microRNAs (miRNAs), non-coding RNAs and mRNAs) are coming to light as valuable biomarkers [ 50 ].…”