Hung Yi-Yung, Chou Chen-Kai, Yang Yi-Chien, Fu Hung-Chun, Loh El-Wui, Kang Hong-Yo
Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan.
Biomedicines. 2021 Oct 9;9(10):1428. doi: 10.3390/biomedicines9101428.
The intracellular microRNAs that negatively regulate Toll-like receptor 4 signaling pathways in peripheral blood mononuclear cells are associated with major depressive disorder (MDD). However, that the distribution of these microRNAs in exosomes could be a biomarker of central nervous system diseases is just beginning to be explored. In the present study, we isolated serum exosomes from patients with MDD and healthy controls to explore the levels of exosomal microRNAs, including let-7e, miR-21-5p, miR-223, miR-145, miR-146a, and miR-155. We also investigated the changes of these exosomal microRNAs after antidepressant treatment and their association with clinical changes in scores on the Hamilton Depression Rating Scale. An ANCOVA adjusted by age, sex, BMI, and smoking showed higher expression levels of miR-146a ( = 0.006) in patients with MDD compared to controls. Patients who achieved remission showed significantly lower let-7e, miR-21-5p, miR-145, miR-146a, and miR-155 levels before treatment and increased levels after antidepressant treatment compared with the non-remission group. Through receiver operating characteristic (ROC) analysis, let-7e, miR-145, and miR-146a showed acceptable discrimination between the remission and non-remission groups, whereas miR-21-5p and miR-155 showed poor discrimination. These findings demonstrate that exosomal microRNAs may play essential roles in predicting antidepressants response.
外周血单核细胞中负向调节Toll样受体4信号通路的细胞内微小RNA与重度抑郁症（MDD）相关。然而，这些微小RNA在外泌体中的分布作为中枢神经系统疾病生物标志物的研究才刚刚开始。在本研究中，我们从MDD患者和健康对照者中分离血清外泌体，以探究外泌体微小RNA的水平，包括let-7e、miR-21-5p、miR-223、miR-145、miR-146a和miR-155。我们还研究了抗抑郁治疗后这些外泌体微小RNA的变化及其与汉密尔顿抑郁量表评分临床变化的关联。经年龄、性别、体重指数和吸烟情况校正的协方差分析显示，与对照组相比，MDD患者中miR-146a的表达水平更高（P = 0.006）。达到缓解的患者在治疗前let-7e、miR-21-5p、miR-145、miR-146a和miR-155的水平显著低于未缓解组，抗抑郁治疗后水平升高。通过受试者工作特征（ROC）分析，let-7e、miR-145和miR-146a在缓解组和未缓解组之间显示出可接受的区分度，而miR-21-5p和miR-155的区分度较差。这些发现表明，外泌体微小RNA可能在预测抗抑郁反应中发挥重要作用。
