压力、表观遗传学与抑郁：系统综述。

Stress, epigenetics and depression: A systematic review.

机构信息

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

出版信息

Neurosci Biobehav Rev. 2019 Jul;102:139-152. doi: 10.1016/j.neubiorev.2019.04.010. Epub 2019 Apr 18.

DOI:10.1016/j.neubiorev.2019.04.010

PMID:31005627

Abstract

Environmental stressors, such as childhood maltreatment, have been recognized to contribute to the development of depression. Growing evidence suggests that epigenetic changes are a key mechanism by which stressors interact with the genome leading to stable changes in DNA structure, gene expression, and behaviour. The current review aimed to evaluate the relationship between stress-associated epigenetic changes and depression. Human studies were identified via systematic searching of PubMed/Medline from inception to February 2018. Seventeen articles were identified. Stress-associated epigenetic changes in the following genes were correlated with depression: NRC31, SLCA4, BDNF, FKBP5, SKA2, OXTR, LINGO3, POU3F1 and ITGB1. Epigenetic changes in glucocorticoid signaling (e.g., NR3C1, FKBP5), serotonergic signaling (e.g. SLC6A4), and neurotrophin (e.g., BDNF) genes appear to be the most promising therapeutic targets for future research. However, continued research is warranted due to inconsistent findings regarding the directionality of epigenetic modification. Future studies should also aim to control for the use of psychotropic agents due to their widespread use in depressed populations and established effects on DNA methylation.

摘要

环境应激源，如儿童期虐待，已被认为是导致抑郁发生的因素之一。越来越多的证据表明，表观遗传变化是应激源与基因组相互作用导致 DNA 结构、基因表达和行为稳定改变的关键机制。本综述旨在评估与应激相关的表观遗传变化与抑郁之间的关系。通过系统检索 PubMed/Medline 从创建到 2018 年 2 月的数据，确定了人类研究。共确定了 17 篇文章。以下基因中的应激相关表观遗传变化与抑郁相关：NRC31、SLCA4、BDNF、FKBP5、SKA2、OXTR、LINGO3、POU3F1 和 ITGB1。糖皮质激素信号（如 NR3C1、FKBP5）、5-羟色胺能信号（如 SLC6A4）和神经营养因子（如 BDNF）基因的表观遗传变化似乎是未来研究最有前途的治疗靶点。然而，由于关于表观遗传修饰的方向性的研究结果不一致，因此需要继续研究。未来的研究还应旨在控制抗精神药物的使用，因为这些药物在抑郁人群中的广泛应用以及对 DNA 甲基化的既定影响。