Circulating microRNA 134 sheds light on the diagnosis of major depressive disorder

Abstract

Major depressive disorder (MDD) is a prevalent and debilitating psychiatric mood disorder that lacks objective laboratory-based tests to support its diagnosis. A class of microRNAs (miRNAs) has been found to be centrally involved in regulating many molecular processes fundamental to central nervous system function. Among these miRNAs, miRNA-134 (miR-134) has been reported to be related to neurogenesis and synaptic plasticity. In this study, the hypothesis that plasma miR-134 can be used to diagnose MDD was tested. Perturbation of peripheral and central miR-134 in a depressive-like rat model was also examined. By reverse-transcription quantitative PCR, miR-134 was comparatively measured in a small set of plasma samples from MDD and healthy control (HC) subjects. To determine its diagnostic efficacy, plasma miR-134 levels were assessed in 100 MDD, 50 bipolar disorder (BD), 50 schizophrenic (SCZ), and 100 HC subjects. A chronic unpredictable mild stress (CUMS) rat model was also developed to evaluate miR-134 expression in plasma, hippocampus (HIP), prefrontal cortex (PFC), and olfactory bulb. We found that plasma miR-134 was significantly downregulated in MDD subjects. Diagnostically, plasma miR-134 levels could effectively distinguish MDD from HC with 79% sensitivity and 84% specificity, while distinguishing MDD from HC, BD, and SCZ subjects with 79% sensitivity and 76.5% specificity. Congruent with these clinical findings, CUMS significantly reduced miR-134 levels in the rat plasma, HIP, and PFC. Although limited by the relatively small sample size, these results demonstrated that plasma miR-134 displays potential ability as a biomarker for MDD.

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“…Developing an objectively diagnostic method with high speci city and sensitivity for MDD has been proven to be a formidable and elusive task, although we and other researchers have completed many meaningful works [16][17][18][19]. In the present work, a potential biomarker panel consisting of AAT, ALB and APOA was identi ed.…”

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“…Developing an objectively diagnostic method with high speci city and sensitivity for MDD has been proven to be a formidable and elusive task, although we and other researchers have completed many meaningful works [14][15][16][17]. In the present work, a potential biomarker panel consisting of AAT, ALB and APOA was identi ed.…”

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“…Plasma miR-134 (associated with the regulation of synaptic plasticity and neurogenesis) was downregulated in a cohort of patients with MDD compared with healthy controls. Measurements of miR-134 patterns are also useful to distinguish between MDD, bipolar disorder and schizophrenia [ 46 ]. Further, an increased expression of miR-124-3p has been detected in serum of antidepressant-free MDD patients compared with healthy controls [ 47 ].…”