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表观遗传学与抑郁症:当前的挑战和新的治疗选择。

Epigenetics and depression: current challenges and new therapeutic options.

机构信息

Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.

出版信息

Curr Opin Psychiatry. 2010 Nov;23(6):588-92. doi: 10.1097/YCO.0b013e32833d16c1.

Abstract

PURPOSE OF REVIEW

Epigenetics comprises heritable but concurrent variable modifications of genomic DNA defining gene expression. The aim of this publication is to review the field of epigenetics in depression. Within this scope, we outline potential therapeutic options evolving in this young field of psychiatric research.

RECENT FINDINGS

Recently published papers show that epigenetic mechanisms like histone modifications and DNA methylation affect diverse pathways leading to depression-like behaviors in animal models. Adverse alterations of gene expression profiles, including glucocorticoid receptor or brain-derived neurotrophic factor, were shown to be inducible by early life stress and reversible by epigenetic drugs. Postmortem studies revealed epigenetic changes in the frontal cortex of depressed suicide victims. There exists profound evidence for histone deacetylase inhibitors to be a novel line of effective antidepressants via counteracting previously acquired adverse epigenetic marks.

SUMMARY

Because of the complex causal factors leading to depression, epigenetics is of considerable interest for the understanding of early life stress in depression. The current research regarding epigenetic pharmaceuticals is promising and deserves further attention in depression and psychiatry in general, and may strike out new ways towards individually tailored therapies.

摘要

目的综述

表观遗传学包括基因组 DNA 定义基因表达的可遗传但同时可变的修饰。本出版物的目的是综述抑郁症中的表观遗传学领域。在这一范围内,我们概述了在这一精神科研究的新兴领域中不断发展的潜在治疗选择。

最近的发现

最近发表的论文表明,表观遗传机制,如组蛋白修饰和 DNA 甲基化,影响导致动物模型出现抑郁样行为的多种途径。研究表明,糖皮质激素受体或脑源性神经营养因子等基因表达谱的不利改变可由早期生活应激诱导,并可通过表观遗传药物逆转。尸检研究显示,抑郁自杀者的前额叶皮层存在表观遗传变化。组蛋白去乙酰化酶抑制剂通过对抗先前获得的不利表观遗传标记,成为一种新型有效的抗抑郁药,这一现象提供了深刻的证据。

总结

由于导致抑郁症的复杂因果因素,表观遗传学对于理解抑郁症中的早期生活应激具有重要意义。目前关于表观遗传学药物的研究很有前景,值得在抑郁症和一般精神病学中进一步关注,并可能为个体化治疗开辟新途径。

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