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.
Highlights
Major depressive disorder (MDD) is a heterogenous disease, involving genetic and environmental factors
Patient enrollment The MDD, bipolar disorder (BD), and healthy control (HC) subjects were recruited from the First Affiliated Hospital of Chongqing Medical University, and SCZ subjects were enrolled from Chongqing Municipal Mental Hospital
MDD, BD, and SCZ subjects were diagnosed by two licensed psychiatrists independently according to DSM-IV criteria and disease severity was evaluated through the Hamilton Rating Scale for Depression (HAM-D, 17-item version)[30], the Beck Depression Inventory (BDI, 13-item version)[31], the Beck-Rafaelsen Manic Scale[32], and the Positive and Negative Syndrome Scale[33], respectively
Summary
Major depressive disorder (MDD) is a heterogenous disease, involving genetic and environmental factors. It has a lifetime prevalence of 16.6% Its diagnosis still relies on subjective assessment of patient symptoms[7], rather than on objective laboratory-based testing, much work has been done to identify biomarkers for its objective diagnosis[8,9,10]. This may lead to underdiagnosis and misdiagnosis in primary care settings, where general practitioners make routine diagnoses of depression[11]. The determination of biomarkers for MDD is necessary to increase diagnostic efficiency and facilitate patient care
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