Reduced ENA78 levels as novel biomarker for major depressive disorder and venlafaxine efficiency: Result from a prospective longitudinal study

Reduced ENA78 levels as novel biomarker for major depressive disorder and venlafaxine efficiency: Result from a prospective longitudinal study
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DOI:
10.1016/j.psyneuen.2017.03.015
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发表时间:
2017-07-01
影响因子:
3.7
通讯作者:
Fang, Yiru
Fang, Yiru
中科院分区:
医学2区
文献类型:
--
作者:
Li, Zezhi;Wang, Zuowei;Fang, Yiru

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尽管一系列证据表明细胞因子在重度抑郁症 (MDD) 的发病机制中发挥着重要作用,但它们都尚未被确定为可靠的生物标志物。我们利用之前的全基因组 cRNA 微阵列数据来鉴定上皮细胞源性中性粒细胞激活肽 78 (ENA78),这是 MDD 患者和健康对照者外周血中表达差异最大的细胞因子;然后,我们在独立的首次药物首次样本集中,分别通过定量逆转录聚合酶链式反应 (RT-qPCR) 和酶联免疫吸附测定 (ELISA) 确认了 mRNA 和蛋白质水平的结果。此外,为了复制血浆ENA 78在MDD中的作用,并确定ENA78对文拉法辛效率的作用,我们进一步在另一个独立的8周随访样本组中检测血浆ENA78。我们发现MDD患者中ENA78的mRNA和血浆均下降,并且在文拉法辛治疗后表现得更低。我们还发现,文拉法辛无反应者在治疗前的外周血浆 ENA78 水平低于反应者。我们的研究结果首次提供了强有力的证据,证明 ENA78 可能在 MDD 发病机制和文拉法辛作用 MDD 的机制中发挥关键作用,表明 ENA78 减少可能是诊断 MDD 和预测文拉法辛反应的潜在生物标志物。 (C) 2017 Elsevier Ltd. 保留所有权利。
Although lines of evidence demonstrated that cytokines play an important role in the pathogenesis of major depressive disorder (MDD), none of the them have been established as reliable biomarkers. We use our previous whole-genome cRNA microarray data to identify epithelial cell-derived neutrophilactivating peptide 78 (ENA78), the most differentially expressed cytokine in peripheral blood between MDD patients and healthy controls; and then we confirmed the result by the quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) for mRNA and protein level, respectively, in an independent drug-naive first-episode sample set. In addition, to replicate the role of plasma ENA 78 in MDD, and determine the role of ENA78 on the venlafaxine efficiency, we further detected the plasma ENA78 in another independent 8- week follow-up sample set. We found that both of mRNA and plasma of ENA78 decreased in MDD patients, and displayed much lower after venlafaxine treatment. We also found that venlafaxine non-responders had lower level of peripheral plasma ENA78 prior to treatment than responders. Our findings for the first time provided strong evidence that the ENA78 may play a key role of mediator in pathogenesis of MDD and in the mechanism of vinlafaxine effects on MDD indicating that reduced ENA78 may be a potential biomarker for diagnosing of MDD and predicting of response to venlafaxine. (C) 2017 Elsevier Ltd. All rights reserved.