关键词: BDNF methylation Childhood trauma Epigenetics Gene × environment Genotype-coding Oxytocin receptor gene

Mesh : Adverse Childhood Experiences Brain-Derived Neurotrophic Factor / genetics DNA Methylation Epigenesis, Genetic Humans Receptors, Oxytocin / genetics

来  源:   DOI:10.1016/j.jad.2022.03.020

Abstract:
Gene-Environment (G × E) interaction is of increasing importance in understanding the pathophysiology of posttraumatic stress disorder (PTSD). This study investigated the interaction effect of childhood traumatic experience and epigenetic methylation of brain-derived neurotrophic factor (BDNF) and a possible moderating effect of oxytocin receptor (OXTR) gene rs53576.
Ninety-nine patients with PTSD and 81 healthy controls (HCs) were recruited. Clinical assessments, including the childhood trauma questionnaire (CTQ) and posttraumatic stress disorder Checklist (PCL) were performed. BDNF methylation and OXTR genotyping (A vs. G allele) were conducted through blood sampling. A two-way multivariate analysis and a moderated regression analysis were conducted to investigate the moderating effect of the OXTR gene on the relationship between CTQ and BDNF methylation.
As for the HC group, the interaction effect of the CTQ and OXTR genotype was significant on BDNF methylation, and the moderation model showed that CTQ and OXTR group are significant predictors of BDNF methylation. In the G-OXTR type, the high CTQ group showed a greater BDNF methylation level. As for the PTSD group, no interaction or moderation effects were found.
The present study did not control the dosage, duration of medications, and different trauma types and the assessment of childhood trauma was based on self-report.
These results suggested that childhood traumatic experience showed a significant impact on BDNF methylation, and OXTR genes have a moderating effect on this epigenetic mechanism in people who have experienced the childhood traumatic episodes.
摘要:
基因-环境(G×E)相互作用在理解创伤后应激障碍(PTSD)的病理生理学方面越来越重要。这项研究调查了儿童创伤经历与脑源性神经营养因子(BDNF)表观遗传甲基化的相互作用以及催产素受体(OXTR)基因rs53576的可能调节作用。
招募了99名PTSD患者和81名健康对照(HC)。临床评估,包括儿童创伤问卷(CTQ)和创伤后应激障碍清单(PCL)。BDNF甲基化和OXTR基因分型(A与G等位基因)通过血液采样进行。进行了双向多变量分析和适度回归分析,以研究OXTR基因对CTQ和BDNF甲基化之间关系的调节作用。
至于HC组,CTQ和OXTR基因型对BDNF甲基化的交互作用显著,适度模型显示CTQ和OXTR组是BDNF甲基化的显著预测因子。在G-OXTR类型中,高CTQ组显示更高的BDNF甲基化水平。至于创伤后应激障碍组,没有发现相互作用或调节作用。
本研究没有控制剂量,药物的持续时间,不同类型的创伤和儿童创伤的评估是基于自我报告。
这些结果表明,童年创伤经历对BDNF甲基化有显著影响,和OXTR基因对经历过童年创伤的人的这种表观遗传机制有调节作用。
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