Université de Paris, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Paris.
Neurospin, CEA, Gif-sur-Yvette, France.
Psychiatr Genet. 2021 Feb 1;31(1):1-12. doi: 10.1097/YPG.0000000000000267.
Bipolar disorder (BD) is a chronic, disabling disease characterised by alternate mood episodes, switching through depressive and manic/hypomanic phases. Mood stabilizers, in particular lithium salts, constitute the cornerstone of the treatment in the acute phase as well as for the prevention of recurrences. The pathophysiology of BD and the mechanisms of action of mood stabilizers remain largely unknown but several pieces of evidence point to gene x environment interactions. Epigenetics, defined as the regulation of gene expression without genetic changes, could be the molecular substrate of these interactions. In this literature review, we summarize the main epigenetic findings associated with BD and response to mood stabilizers.
We searched PubMed, and Embase databases and classified the articles depending on the epigenetic mechanisms (DNA methylation, histone modifications and non-coding RNAs).
We present the different epigenetic modifications associated with BD or with mood-stabilizers. The major reported mechanisms were DNA methylation, histone methylation and acetylation, and non-coding RNAs. Overall, the assessments are poorly harmonized and the results are more limited than in other psychiatric disorders (e.g. schizophrenia). However, the nature of BD and its treatment offer excellent opportunities for epigenetic research: clear impact of environmental factors, clinical variation between manic or depressive episodes resulting in possible identification of state and traits biomarkers, documented impact of mood-stabilizers on the epigenome.
Epigenetic is a growing and promising field in BD that may shed light on its pathophysiology or be useful as biomarkers of response to mood-stabilizer.
双相情感障碍（BD）是一种慢性、致残性疾病，其特征为情绪发作交替出现，通过抑郁和躁狂/轻躁狂阶段进行切换。心境稳定剂，特别是锂盐，构成了急性期治疗以及预防复发的基石。BD 的病理生理学和心境稳定剂的作用机制在很大程度上仍然未知，但有一些证据表明存在基因 x 环境相互作用。表观遗传学定义为没有遗传变化的基因表达调控，可能是这些相互作用的分子基础。在这篇文献综述中，我们总结了与 BD 和对心境稳定剂的反应相关的主要表观遗传学发现。
我们搜索了 PubMed 和 Embase 数据库，并根据表观遗传学机制（DNA 甲基化、组蛋白修饰和非编码 RNA）对文章进行了分类。
我们提出了与 BD 或与心境稳定剂相关的不同表观遗传修饰。主要报道的机制是 DNA 甲基化、组蛋白甲基化和乙酰化以及非编码 RNA。总体而言，评估的协调性较差，结果比其他精神障碍（如精神分裂症）更为有限。然而，BD 的性质及其治疗为表观遗传学研究提供了极好的机会：环境因素的明显影响、躁狂或抑郁发作之间的临床差异导致可能识别状态和特征生物标志物，以及心境稳定剂对表观基因组的有记录影响。
表观遗传学是 BD 领域中一个不断发展和有前途的领域，它可能揭示其病理生理学，或作为对心境稳定剂反应的生物标志物有用。
