Gururajan A, Naughton M E, Scott K A, O'Connor R M, Moloney G, Clarke G, Dowling J, Walsh A, Ismail F, Shorten G, Scott L, McLoughlin D M, Cryan J F, Dinan T G
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.
Transl Psychiatry. 2016 Aug 2;6(8):e862. doi: 10.1038/tp.2016.131.
There is a growing emphasis in the field of psychiatry on the need to identify candidate biomarkers to aid in diagnosis and clinical management of depression, particularly with respect to predicting response to specific therapeutic strategies. MicroRNAs are small nucleotide sequences with the ability to regulate gene expression at the transcriptomic level and emerging evidence from a range of studies has highlighted their biomarker potential. Here we compared healthy controls (n=20) with patients diagnosed with major depression (n=40) and who were treatment-resistant to identify peripheral microRNA biomarkers, which could be used for diagnosis and to predict response to electroconvulsive therapy (ECT) and ketamine (KET) infusions, treatments that have previously shown to be effective in treatment-resistant depression (TRD). At baseline and after treatment, blood samples were taken and symptom severity scores rated using the Hamilton Depression Rating Scale (HDRS). Samples were analyzed for microRNA expression using microarray and validated using quantitative PCR. As expected, both treatments reduced HDRS scores. Compared with controls, the baseline expression of the microRNA let-7b was less by ~40% in TRD patients compared with controls. The baseline expression of let-7c was also lower by ~50% in TRD patients who received ECT. Bioinformatic analysis revealed that let-7b and let-7c regulates the expression of 27 genes in the PI3k-Akt-mTOR signaling pathway, which has previously been reported to be dysfunctional in depression. The expression of miR-16, miR-182, miR-451 and miR-223 were similar to that in controls. Baseline microRNA expression could not predict treatment response and microRNAs were unaffected by treatment. Taken together, we have identified let-7b and let-7c as candidate biomarkers of major depression.
精神病学领域越来越强调需要识别候选生物标志物，以辅助抑郁症的诊断和临床管理，特别是在预测对特定治疗策略的反应方面。微小RNA是具有在转录组水平调节基因表达能力的小核苷酸序列，一系列研究的新证据凸显了它们作为生物标志物的潜力。在这里，我们将健康对照者（n = 20）与被诊断为重度抑郁症且对治疗耐药的患者（n = 40）进行比较，以识别外周微小RNA生物标志物，这些生物标志物可用于诊断以及预测对电休克治疗（ECT）和氯胺酮（KET）输注的反应，ECT和KET输注此前已被证明对难治性抑郁症（TRD）有效。在基线和治疗后，采集血样并使用汉密尔顿抑郁量表（HDRS）对症状严重程度评分。使用微阵列分析样本中的微小RNA表达，并通过定量PCR进行验证。正如预期的那样，两种治疗均降低了HDRS评分。与对照组相比，TRD患者中微小RNA let-7b的基线表达比对照组低约40%。接受ECT的TRD患者中let-7c的基线表达也低约50%。生物信息学分析表明，let-7b和let-7c调节PI3k-Akt-mTOR信号通路中27个基因的表达，此前有报道称该信号通路在抑郁症中功能失调。miR-16、miR-182、miR-451和miR-223的表达与对照组相似。基线微小RNA表达无法预测治疗反应，且微小RNA不受治疗影响。综上所述，我们已将let-7b和let-7c确定为重度抑郁症的候选生物标志物。
