Preliminary Investigation of Peripheral Extracellular Vesicles' MicroRNAs in Bipolar Disorder

Background: The 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.

Methods: We 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.

Results: Our 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.

Limitations: Relatively 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.

Conclusions: This 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.