Distribution of microRNAs associated with major depressive disorder among blood compartments

Objective Major depressive disorder (MDD) is a recurrent disorder with an increasing incidence. Alterations in key signaling pathways of the nervous system, such as the Wnt and MAPK pathways, mediated through microRNAs (miRNAs) provide crucial information regarding the etiopathology of MDD. We aimed to analyze whether the heterogeneity of literature findings regarding differential expression of miRNAs in the blood could arise from their different distributions among blood compartments. Methods We performed a pilot study analyzing the differential expression of miR-26a, miR-494, miR-30c, miR-93, and miR-101 and investigated their levels in white blood cells, total plasma (TP), exosomes from plasma, and exosome depleted plasma (EDP) in patients with MDD before and after antidepressant treatment with escitalopram and in healthy controls. Results MiR-494 was more abundant in EDP, and miR-26a and miR-30c were predominantly more abundant in TP relative to other blood compartments. Moreover, miR-30c, miR-101, and miR-26a, were significantly downregulated in TP of patients with MDD compared with controls. After antidepressant treatment, only miR-494 was significantly differently expressed in EDP. Conclusions This proof-of-principle study suggests that identifying the miRNA abundance in different blood compartments is crucial for biomarker development and could enrich the current knowledge regarding MDD pathophysiology.

Automated summary

This study analyzed the differential expression of miRNAs in different blood compartments in MDD patients and found that miR-494 was more abundant in EDP, while miR-26a and miR-30c were predominantly more abundant in TP. MiR-30c, miR-101, and miR-26a were significantly downregulated in TP of MDD patients compared to controls. After antidepressant treatment, only miR-494 showed significant differential expression in EDP.