Circulating exosomal microRNAs in bipolar disorder

Introduction: Emerging evidence suggests central roles of miRNAs in the pathogenesis of bipolar disorder (BD). Exosomes are membrane-bound vesicles acing as "biological cargo carriers" of various types of molecules including microRNAs. In this study, we aimed to investigate circulating exosomal microRNAs as potential diagnostic biomarkers for BD. Methods: The exosomes were precipitated from plasma samples of patients with BD (n = 69; 15 depressed, 27 manic, 27 euthymic) and healthy controls (n. = 41). Total RNA was extracted from the exosomes and the levels of miRNAs were assayed by qPCR. Dysregulated miRNAs were subjected to Kyoto Encyclopedia of Genes and Genomes" (KEGG) pathway analysis by DIANA-miRPath v3.0 to identify the predicted targets and the related pathways. Results: Thirteen miRNAs showed significant differences between patients with BD and healthy individuals; among these, MiR-484, -652-3p, -142-3p remained significantly downregulated and miR-185-5p remained significantly upregulated after accounting for multiple comparisons and adjustments for potential confounders. There were no significant alterations among different states of BD. The KEEG analysis of four dysregulated miRNAs highlighted several target pathways including PI3K/Akt signaling, fatty acid biosynthesis/metabolism, extracellular matrix and adhesion pathways. Conclusion: Our findings suggest that dysregulation of miRNAs might be involved in the underlying pathophysiology of BD through several biological pathways; and highlight the importance of the exosomal miRNAs for biomarker research in BD. Further longitudinal studies may clarify the roles of exosomal miRNAs and their targets in the neurobiology of BD.