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.