miR-34a表达调控紊乱与抑郁障碍和抗抑郁疗效的关联研究

Study on the association of dysregulation of miR-34a expression with depressive disorder and antidepressant efficacy

目的比较抑郁障碍患者和正常对照外周血浆miR-34a的表达情况,及抗抑郁药物对miR-34a表达的影响,以寻找抑郁障碍相关的生物学标志和抗抑郁治疗生物学预测指标。方法收集82例首发未用药抑郁障碍患者和60名正常对照,采用实时荧光定量PCR方法检测其外周血浆miR-34a的表达水平。患者接受8周规范化抗抑郁药物治疗,根据汉密尔顿抑郁量表(Hamilton depression scale,HAMD)总分判断患者是否临床治愈和显效,并再次检测外周血浆miR-34a表达水平。结果miR-34a在患者组表达高于对照组(P=0.001)。治疗后抑郁障碍患者组miR-34a表达水平明显降低(P=0.032),仍高于对照组(P=0.001)。治愈组和未愈组,以及显效组和非显效组,miR-34ap表达水平治疗前后差异无统计学意义(P>0.05)。ROC曲线分析显示miR-34a表达水平区分患者与对照的AUC为0.849(95%CI:0.787~0.911),取最佳界值点时敏感度为76.8%,特异度为85.0%。结论抑郁障碍患者外周血浆miR-34a高表达,经抗抑郁药物治疗后miR-34a表达水平降低。miR-34a表达水平可能对抑郁障碍诊断具有价值。

Objective To compare the expression of miR-34a in peripheral plasma of patients with depression and the normal control group,and the effect of antidepressant drugs on the expression of miR-34a,in order to find biological markers related to depression and biological predictors of antidepressant therapy.Methods A total of 82 patients with first-episode unused depressive disorder and 60 normal controls were recruited.The peripheral plasma miR-34a expression levels were examined by using real-time fluorescent quantitative PCR method.The patients received 8 weeks of standardized antidepressant treatment.The Hamilton Depression Scale(HAMD)total score was used to evaluate the efficacy of antidepressant.Results The expression of miR-34a was higher in the patient group than in the control group(P=0.001).The expression level of miR-34a in the depressive disorder group was significantly reduced after treatment(P=0.032),and was still higher compared with the control group(P=0.001).There was no significant difference in the expression level of miR-34a-5p before and after treatment in all treatment groups including the cured group,the markedly effective group,the non-markedly effective group and unhealed group(all P>0.05).ROC curve analysis showed that the AUC of miR-34a expression level to distinguish patients from controls was 0.849(95%CI:0.787~0.911).The sensitivity and specificity were 76.8%and 85.0%,respectively when the best cut-off point was selected.Conclusion The peripheral plasma miR-34a is highly expressed in patients with depressive disorder and the expression level of miR-34a is reduced after antidepressant treatment.The expression level of miR-34a may be valuable for the diagnosis of depression.