Examining redox modulation pathways in the post-mortem frontal cortex in patients with bipolar disorder through data mining of microRNA expression datasets.

The etiology of redox (reduction and oxidation) alterations in bipolar disorder (BD) is largely unknown. To explore whether microRNAs targeting redox enzymes may have a role in BD, we examined 3 frontal cortex microRNA expression datasets (Perkins [2007], Vladimirov [2009], and Miller [2009]; N for BD = 30-36 per dataset, N for controls = 28-34 per dataset) from the Stanley Neuropathology Consortium. Each dataset was analyzed separately because they were generated using different high-throughput platforms. Following the selection of only redox modulator-targeting microRNAs, microRNAs in the top 10th percentile in feature selection could together discriminate BD and controls at a greater frequency than expected by chance in classification analysis. In pathway enrichment analysis of all three datasets, these classifying microRNAs targeted the cellular nitrogen compound metabolic process pathway, which includes redox enzymes of the mitochondrial electron transport chain and the glutathione system. To see if this pathway would still emerge as significant if all microRNAs (not just redox-targeting) were analyzed, all analyses were repeated with the complete set of microRNAs. Cellular nitrogen compound metabolic process pathway was enriched in all 3 datasets in this analysis as well, demonstrating that preselection of redox microRNAs was not a requirement to identify this pathway for the discrimination of BD and controls. While preliminary, our findings suggest that microRNAs that target redox enzymes in this pathway may be good candidates for the exploration of causative factors contributing to redox alterations in BD. Future studies validating these findings in a separate set of central and peripheral samples are warranted.