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P11 甲基化与早期生活应激的相互作用影响了重度抑郁症患者的抗抑郁反应。

The interaction of P11 methylation and early-life stress impacts the antidepressant response in patients with major depressive disorder.

机构信息

Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, PR China.

Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, PR China; Department of Sleep Medicine, The Fourth People's Hospital of Lianyungang, Lianyungang 222000, PR China.

出版信息

J Affect Disord. 2022 Sep 1;312:128-135. doi: 10.1016/j.jad.2022.06.042. Epub 2022 Jun 23.

DOI:10.1016/j.jad.2022.06.042
PMID:35752218
Abstract

PURPOSE

The present research investigates the influence of P11 gene DNA methylation combined with life stress on the response to antidepressants in the first two weeks.

METHODS

A total of 291 Han Chinese patients with major depressive disorder and 100 healthy controls were included. The Life Events Scale and the Childhood Trauma Questionnaire were used to assess stress. The primary endpoint was the Hamilton Depression Rating Scale-17 reduction rate after two weeks of treatment. The Illumina HiSeq Platform was used to detect the methylation of 74 CpG sites of the P11 gene in peripheral blood samples.

RESULTS

The mean methylation of all P11 CpG sites, as well as the methylation at 4 CpG sites (P11-2-169, P11-2-192, P11-2-202, P11-2-204), were significantly higher in patients with MDD than in healthy controls (FDR-corrected P < 0.05). The response to antidepressants was associated with the following interactions: the CTQ score and P11-3-185 site methylation (OR = 0.297, FDR-corrected P = 0.023), the CTQ physical neglect score and P11-2-117 site methylation (OR = 0.005, FDR-corrected P = 0.033), and the CTQ emotional abuse score and P11-3-185 site methylation (OR = 0.001, FDR-corrected P = 0.023).

CONCLUSIONS

The methylation of the P11 gene was significantly higher in patients with major depressive disorder. The interaction of P11 DNA methylation and early-life stress may influence the short-term antidepressant treatment response.

摘要

目的

本研究旨在探讨 P11 基因 DNA 甲基化与生活应激相结合对前两周抗抑郁药物反应的影响。

方法

共纳入 291 例汉族首发抑郁症患者和 100 例健康对照者。采用生活事件量表和儿童期创伤问卷评估应激。主要终点是治疗两周后汉密尔顿抑郁量表-17 减分率。采用 Illumina HiSeq 平台检测外周血样本中 P11 基因 74 个 CpG 位点的甲基化。

结果

MDD 患者的所有 P11 CpG 位点以及 4 个 CpG 位点(P11-2-169、P11-2-192、P11-2-202、P11-2-204)的平均甲基化水平显著高于健康对照组(FDR 校正 P<0.05)。抗抑郁药物反应与以下交互作用相关:童年期创伤问卷总分与 P11-3-185 位点甲基化(OR=0.297,FDR 校正 P=0.023)、童年期创伤问卷躯体忽视评分与 P11-2-117 位点甲基化(OR=0.005,FDR 校正 P=0.033)、童年期创伤问卷情感虐待评分与 P11-3-185 位点甲基化(OR=0.001,FDR 校正 P=0.023)。

结论

首发抑郁症患者 P11 基因甲基化水平显著升高。P11 DNA 甲基化与早期生活应激的相互作用可能影响短期抗抑郁治疗反应。

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