Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential

Signal Transduction and Targeted Therapy

Review Article

Biao Yang¹  Canhua Huang²  Gerson Rothschild³  Chuang Wang⁴  J. John Mann⁵  Minlan Yuan⁶  Wei Zhang⁷  Xiangdong Tang⁸  Larry D. Sanford⁹ 

[1] Department of Abdominal Oncology, West China Hospital, Sichuan University, 610041, Chengdu, China;Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, China;Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, 10032, New York, NY, USA;Department of Pharmacology, and Provincial Key Laboratory of Pathophysiology in School of Medicine, Ningbo University, 315211, Ningbo, Zhejiang, China;Department of Psychiatry, Columbia University, 10032, New York, NY, USA;Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, 10032, New York, NY, USA;Department of Radiology, Columbia University, 10032, New York, NY, USA;Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, China;Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, China;West China Biomedical Big Data Center, West China Hospital, Sichuan University, 610041, Chengdu, China;Medical Big Data Center, Sichuan University, 610041, Chengdu, China;Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Mental Health Center, Translational Neuroscience Center, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, China;Sleep Research Laboratory, Center for Integrative Neuroscience and Inflammatory Diseases, Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA, USA;

关键词: ;   

DOI  :  10.1038/s41392-023-01519-z

 received in 2022-11-17, accepted in 2023-05-31,  发布年份 2023

来源: Springer

【 摘 要 】

Major depressive disorder (MDD) is a chronic, generally episodic and debilitating disease that affects an estimated 300 million people worldwide, but its pathogenesis is poorly understood. The heritability estimate of MDD is 30–40%, suggesting that genetics alone do not account for most of the risk of major depression. Another factor known to associate with MDD involves environmental stressors such as childhood adversity and recent life stress. Recent studies have emerged to show that the biological impact of environmental factors in MDD and other stress-related disorders is mediated by a variety of epigenetic modifications. These epigenetic modification alterations contribute to abnormal neuroendocrine responses, neuroplasticity impairment, neurotransmission and neuroglia dysfunction, which are involved in the pathophysiology of MDD. Furthermore, epigenetic marks have been associated with the diagnosis and treatment of MDD. The evaluation of epigenetic modifications holds promise for further understanding of the heterogeneous etiology and complex phenotypes of MDD, and may identify new therapeutic targets. Here, we review preclinical and clinical epigenetic findings, including DNA methylation, histone modification, noncoding RNA, RNA modification, and chromatin remodeling factor in MDD. In addition, we elaborate on the contribution of these epigenetic mechanisms to the pathological trait variability in depression and discuss how such mechanisms can be exploited for therapeutic purposes.

【 授权许可】

CC BY   
© West China Hospital, Sichuan University 2023

【 图 表 】

Fig. 2

Fig. 4

Fig. 1

13690_2023_1147_Article_IEq20.gif

Fig. 2

Fig. 2

Fig. 3