Abstract
Extracellular vesicles (EVs) are cell-derived structures that transport proteins, lipids and nucleic acids between cells, thereby affecting the phenotype of the recipient cell. As the content of EVs reflects the status of the originating cell, EVs can have potential as biomarkers. Identifying EVs, including their cells of origin and their cargo, may provide insights in the pathophysiology of psychosis. Here, we present an in-depth analysis and proteomics of EVs from peripheral blood in patients (n = 25) during and after the acute phase of psychosis. Concentration and protein content of EVs in psychotic patients were twofold higher than in 25 age- and sex-matched healthy controls (p < 0.001 for both concentration and protein content), and the diameter of EVs was larger in patients (p = 0.02). Properties of EVs did not differ significantly in blood sampled during and after the acute psychotic episode. Proteomic analyses on isolated EVs from individual patients revealed 1,853 proteins, whereof 45 were brain-elevated proteins. Of these, five proteins involved in regulation of plasticity of glutamatergic synapses were significantly different in psychotic patients compared to controls; neurogranin (NRGN), neuron-specific calcium-binding protein hippocalcin (HPCA), kalirin (KALRN), beta-adducin (ADD2) and ankyrin-2 (ANK2). To summarize, our results show that peripheral EVs in psychotic patients are different from those in healthy controls and point at alterations on the glutamatergic system. We suggest that EVs allow investigation of blood-borne brain-originating biological material and that their role as biomarkers in patients with psychotic disorders is worthy of further exploration.
Highlights
Extracellular vesicles (EVs) are nanoscale (30–1,000 nm), cell-derived, double-lipid membrane structures containing proteins, RNAs and lipids (Van Niel, D’Angelo & Raposo, 2018; Yanez-Mo et al, 2015)
We found that the size, concentration and protein content of EVs from psychotic patients differed significantly from healthy controls (Table 1A)
Use of illegal substances or duration of the psychotic disorder had no influence on EV characteristics, indicating that the findings correlate to other factors than an unhealthy life style which is common in patients with psychosis (Jakobsen et al, 2018)
Summary
Extracellular vesicles (EVs) are nanoscale (30–1,000 nm), cell-derived, double-lipid membrane structures containing proteins, RNAs and lipids (Van Niel, D’Angelo & Raposo, 2018; Yanez-Mo et al, 2015). They are secreted from cells by direct budding of the cell membrane (microvesicles) or by exocytosis of multivesicular bodies (exosomes). EVs could be used as therapeutic vehicles, as evidence indicates that their membrane proteins can guide them to specific recipient cells (Van Niel, D’Angelo & Raposo, 2018; Yanez-Mo et al, 2015). There are only four published studies on psychosis and EVs: one based on brain biopsies (Banigan et al, 2013), a case report involving cerebrospinal fluid (CSF) analysis (Mobarrez et al, 2013), and two studies showing altered insulin signaling in L1 cell adhesion molecule (L1CAM) positive EVs in patients with schizophrenia (Kapogiannis et al, 2019a; Wijtenburg et al, 2019)
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