Neural extracellular vesicle-derived miR-17 in blood as a potential biomarker of subthreshold depression

Subthreshold depression (StD) is a depressive state that does not fulfil the criteria for major depressive disorder (MDD); however, StD has a risk for progression to MDD, and early intervention is therefore needed. Recently, a method for extracting neural extracellular vesicles (NEVs) excreted from neural cells of the brain from blood has been established, and microRNAs (miRNAs) encapsulated in NEVs are attracting interest because of their potential correlation to the pathogenesis of psychiatric disorders. However, miRNAs closely related to StD are still unknown. Therefore, to try to identify miRNAs closely related to the degree of StD, we examined the correlations between expression levels of some candidate miRNAs in NEVs and Patient Health Questionnaire-9 (PHQ-9) scores in subjects. Total RNAs in NEVs were extracted from serum of young adult males who had PHQ-9 scores of less than 10 (n = 9). Expression levels of eight miRNAs that were previously reported to be depression-associated miRNAs (let-7a-5p, miR-17-5p, miR-26b-5p, miR-34a-5p, miR-132-3p, miR-182-5p, miR-212-3p, and miR-1202) were measured using real-time PCR. Two of the eight miRNAs (miR-17-5p and miR-26b-5p) were stably detected. The relative expression levels of miR-17-5p showed a significant positive correlation with PHQ-9 scores (r = 0.85, p < 0.01), while those of miR-26b-5p showed no significance. Although a larger-scale analysis is needed due to the small number of subjects, these findings suggest that miR-17-5p in NEVs is a potential biomarker for StD.