Preliminary investigation of peripheral extracellular vesicles’ microRNAs in bipolar disorder

Abstract

BackgroundThe search for biomarkers of bipolar disorder (BD), including epigenetic alterations, has heavily relied on peripheral investigations that do not necessarily reflect brain-specific mechanisms. In this study we aimed to assess peripheral extracellular vesicles (EVs)’ microRNAs and determine their use as a novel source of biomarkers in BD. MethodsWe assessed peripheral blood EVs’ microRNAs from 20 patients with BD type I and 21 age- and sex-matched healthy controls by microarray, and further explored the predicted biological functions of significantly differentially expressed microRNAs. ResultsOur results identified 33 nominally significant microRNAs (p < 0.05 and fold-change >1.5) altered in BD patients, including miRNAs previously reported to be altered in post-mortem tissues of patients. Pathway analyses identified some brain-relevant mechanisms enriched in these miRNAs, including axon guidance by netrin and the serotonin receptor pathway. LimitationsRelatively small sample size, potential confounding effects of mood states, medication use, and comorbidities, analysis of total rather than brain-specific EVs, and lack of validation of significant miRNAs by other methods. ConclusionsThis study provides important preliminary evidence of the potential use of EVs as a novel source of biomarkers in BD. Overall, our findings of brain-relevant mechanisms in these vesicles suggest their potential use in living patients as a peripheral window to the brain.