Fan Hui-min, Sun Xin-yang, Guo Wei, Zhong Ai-fang, Niu Wei, Zhao Lin, Dai Yun-hua, Guo Zhong-min, Zhang Li-yi, Lu Jim
Department of Psychiatry and Psychology, Second Military Medical University, Shanghai 200433, People's Republic of China.
Department of Psychiatry and Psychology, Second Military Medical University, Shanghai 200433, People's Republic of China; Prevention and Treatment Center for Psychological Diseases, No. 102 Hospital of Chinese People's Liberation Army, North Peace Road 55, Changzhou 213003, Jiangsu, People's Republic of China.
J Psychiatr Res. 2014 Dec;59:45-52. doi: 10.1016/j.jpsychires.2014.08.007. Epub 2014 Aug 24.
Currently, diagnosis and treatment of major depressive disorder (MDD) are based on the patients' description of symptoms, mental status examinations, and clinical behavioral observations, which increases the chance of misdiagnosis. There is a serious need to find a practical biomarker for the proper diagnosis of MDD. This study aimed to explore the possibility of microRNA (miRNA) in peripheral blood mononuclear cells (PBMCs) as specific blood-based biomarker for MDD patients. By using an Affymetrix array that covers 723 human miRNAs, we identified 26 miRNAs with significant changes in expression in PBMCs of MDD patients. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis in a larger cohort of 81 MDD patients and 46 healthy controls confirmed that the expression levels of 5 miRNAs (miRNA-26b, miRNA-1972, miRNA-4485, miRNA-4498, and miRNA-4743) were up-regulated. By receiver operating characteristic (ROC) curve analysis, the combining area under the ROC curve (AUC) of these five miRNAs was 0.636 [95% confidence interval (CI): 0.58-0.90]. MiRNA target gene prediction and functional annotation analysis showed that there was a significant enrichment in several pathways associated with nervous system and brain functions, supporting the hypothesis that differentially-regulated miRNAs may be involved in mechanism underlying development of MDD. We conclude that altered expression of miRNAs in PMBCs might be involved in multiple stages of MDD pathogenesis, and thus might be able to serve as specific biomarker for diagnosis of MDD.
目前,重度抑郁症(MDD)的诊断和治疗基于患者对症状的描述、精神状态检查以及临床行为观察,这增加了误诊的可能性。迫切需要找到一种实用的生物标志物来准确诊断MDD。本研究旨在探讨外周血单核细胞(PBMC)中的微小RNA(miRNA)作为MDD患者特异性血液生物标志物的可能性。通过使用覆盖723种人类miRNA的Affymetrix芯片,我们在MDD患者的PBMC中鉴定出26种表达有显著变化的miRNA。在一个更大的队列中,对81例MDD患者和46例健康对照进行实时定量逆转录聚合酶链反应(qRT-PCR)分析,证实5种miRNA(miRNA-26b、miRNA-1972、miRNA-4485、miRNA-4498和miRNA-4743)的表达水平上调。通过受试者工作特征(ROC)曲线分析,这5种miRNA的ROC曲线下联合面积(AUC)为0.636 [95%置信区间(CI):0.58 - 0.90]。miRNA靶基因预测和功能注释分析表明,在与神经系统和脑功能相关的多个途径中存在显著富集,支持了差异调节的miRNA可能参与MDD发病机制的假说。我们得出结论,PMBC中miRNA表达的改变可能参与了MDD发病机制的多个阶段,因此可能能够作为MDD诊断的特异性生物标志物。