抑郁症患者药物治疗前后单核细胞中microRNA表达水平变化与抑郁症状的关系

Relationship between depressive symptoms and miRNA expression level in monocytes of patients with depression before and after antidepressant treatment

目的探讨抑郁症患者药物治疗前后单核细胞中micro RNA(mi RNA)的表达水平与抑郁症状的关系。方法纳入2012年8月-2013年10月解放军102医院收治的81例未经药物治疗、符合DSM-Ⅳ诊断标准的抑郁症患者作为病例组,纳入同期81例正常人作为对照组。抽取3例患者和3例正常人,采用基因芯片筛查出26种mi RNA,然后以实时荧光定量PCR技术检测两组单核细胞中9种mi RNA(mi R-146b、mi R-1972、mi R-26b、mi R-29b、mi R-338、mi R-4485、mi R-4498、mi R-4743和mi R-874)的表达水平。选取病例组中20例患者,分别在用药前和用药(包括文拉法辛、舍曲林、米氮平等)6周后检测mi RNA表达水平,并采用汉密顿抑郁量表(HAMD)和临床疗效总评量表(CGI)对治疗前及治疗6周后的临床症状及疗效进行评估。结果与对照组比较,病例组单核细胞中5种mi RNA(mi R-26b、mi R-4743、mi R-4498、mi R-4485、mi R-1972)表达上调,差异有统计学意义(P<0.05)。抗抑郁药治疗前后,Δmi RNA-1972、Δmi RNA-4485、Δmi RNA-4498、Δmi RNA-4743与阻滞因子的改善程度呈正相关(P<0.05),Δmi RNA-26b与日夜变化因子的改善程度呈负相关(P<0.05)。Logistic回归分析显示,mi RNA-4485能解释阻滞因子变异量的28.8%(P<0.05)。结论抑郁症患者单核细胞中mi R-26b、mi R-4743、mi R-4498、mi R-4485和mi R-1972可能作为反映抑郁症转归的生物标记物。

Objective To explore the correlation of depressive symptoms to the microRNA （miRNA） expression level in monocytes of patients with depression before and after antidepressant treatment. Methods Eighty-one patients with depression, admitted to the 102 Hospital of PLA from Aug. 2012 to Oct. 2013, having not received antidepressants treatment and meeting the criteria as listed in Diagnostic and Statistical Manual 4th edition （DSM-IV）, were selected as case group. Eighty-one normal individuals served as control group. With Affymetrix Expression Array, 26 miRNAs were identified from 3 individuals from each group as candidate miRNA, and among them 9 miRNAs （miR-146b, miR-1972, miR-26b, miR-29b, miR-338, miR-448S, miR-4498, miR-4743 and miR-874） in monocytes were selected for quantitative real-time reverse transcription polymerase chain reaction （RT- PCR） assessment. Twenty patients from the case group were selected for the assessment of miRNA expression levels, and the clinical symptoms and treatment effect were evaluated using Hamilton Depression Scale （HAMD） and Clinical Global Impression （CGI）, before and 6 weeks after antidepressant （venlafaxine, sertraline, mirtazapine, etc.） treatment. Results Compared with the control group, the expression levels of miRNA-26b, miRNA-4743, miRNA-4498, miRNA-4485 and miRNA-1972 of the case group were significantly up-regulated （P〈O.05）. The variance of expression level ofmiRNA-4743, miRNA-4498, miRNA-4485 and miRNA- 1972 was respectively positively correlated with improvement in retardation factors （P〈0.05）, meanwhile the variance of expression level of miRNA-26b was negatively correlated with the improvement of day and night change factors （P〈0.05）. Logistic regression analysis demonstrated that the alteration of miRNA-4485 expression may account 28.8% of retardation variance （P〈0.05）. Conclusion The miRNA-4743, miRNA-4498, miRNA-4485, miRNA-1972 and miRNA-26b in monocytes may serve as the biomarkers for the prognosis of depressive disorder.