MicroRNAs as Candidates for Bipolar Disorder Biomarkers

Bipolar disorder (BD) is a common, recurring psychiatric illness with unknown pathogenesis. Much like other psychiatric diseases, BD suffers from the chronic lack of reliable biomarkers and innovative pharmacological interventions. Better characterization of clinical profiles, experimental medicine, genomic data mining, and the utilization of experimental models, including stem cell and genetically modified mice, are suggested ways forward. Environment, including early childhood experiences, has been documented to modulate the risk for the development of psychiatric disorders via epigenetic mechanisms. Key epigenetic regulators, microRNAs (miRNAs, miRs), govern normal neuronal functioning and show altered expression in diverse brain pathologies. We observed significant alterations of exosomal miR-29c levels in prefrontal cortex (Brodmann area 9, BA9) of BD patients. We also demonstrated that exosomes extracted from the anterior cingulate cortex (BA24), a crucial area for modulating emotional expression and affect, have increased levels of miR-149 in BD patients compared to controls. Because miR-149 has been shown to inhibit glial proliferation, we hypothesized that increased miR-149 expression in BA24-derived exosomes may be consistent with the previously reported reduced glial cell numbers in BA24 of patients diagnosed with familial BD. qPCR analysis of laser-microdissected neuronal and glial cells from BA24 cortical samples of BD patients verified that the glial, but not neuronal, population exhibits significantly increased miR-149 expression. These findings support neuron-glia interaction as a possible target mechanism in BD, implicated by others in neuroimaging, postmortem, and in vivo studies of the pathological changes mediated by glial cells.