Differential microRNA profiling of blood L1CAM and bulk extracellular vesicles in bipolar disorder.

OBJECTIVE: This preliminary study aimed to identify microRNA (miRNA) signatures associated with bipolar disorder (BD) by profiling blood-derived extracellular vesicles (EVs) of both putative neuronal origin and from all sources. METHOD: In two parallel studies of individuals with BD and controls (CON), we characterized miRNA expression profiles of blood EVs selected for L1CAM, a putative marker of neuronal origin (n = 20 BD/20 CON), as well as bulk EVs (n = 21 BD/20 CON). For each study, analyses identified miRNAs differentially expressed between groups, followed by functional interrogation and testing for associations with clinical features. RESULTS: Results of Study 1 showed 34 miRNAs differentially expressed between groups and implicated PTEN, a gene whose protein levels were previously found to be altered in postmortem brain studies of BD. Results of Study 2 showed 10 miRNAs differentially expressed between groups. Limited overlap was identified between studies, with only hsa-miR-1-3p identified with the same direction of change across both types of EVs. Differentially expressed miRNAs were significantly associated with clinical features of BD only in Study 1. CONCLUSIONS: Our results, albeit preliminary, reiterate a crucial role for miRNAs in the pathophysiology of BD and suggest that miRNA signatures of putative neuronal origin may more closely correspond to clinical features.