Dysregulation of MicroRNAs Derived from Plasma Extracellular Vesicles in Schizoaffective Disorder

The association between peripheral blood extracellular vesicles (EVs)-derived miRNAs (EVs-miRNAs) and neuropsychiatric diseases has been extensively studied. However, it remains largely unclear about the expression profile of EVs-miRNAs in schizoaffective disorder (SAD) patients. In our study, we isolated the EVs from plasma samples of patients and healthy controls, and then analyzed the expression profiles of EVs-miRNAs through small RNA sequencing. Our results identified 32 differentially expressed (DE) miRNAs (25 upregulated and 7 downregulated) in SAD patients. A module containing 42 miRNAs closely related to SAD was identified by weighted gene co-expression network analysis (WGCNA), among which has-miR-15b-5p, has-miR-301a-3p, has-miR-342-3p, has-miR-219b-5p, and has-miR-145-5p were identified as hub miRNAs. The enrichment analysis showed that the target genes of these 42 miRNAs were significantly enriched in multiple pathways related to neuropathology and located at synapses. A total of 6 DE miRNAs (has-miR-7-5p, has-miR-144-3p, has-miR-155-5p, has-miR-342-3p, has-miR-342-5p, and has-miR-487b-3p) associated with SAD were selected for qRT-PCR verification. The level of has-miR-342-3p in SAD patients was downregulated, and hsa-miR-155-5p was upregulated. Our findings support the hypothesis that dysregulation of EVs-miRNAs in plasma might be involved in the underlying neuropathology of SAD through several biological pathways and provide important preliminary evidence supporting the use of EVs-miRNAs as potential novel biomarkers in SAD.