Gottschalk Michael G, Domschke Katharina, Schiele Miriam A
Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Center for Basics in NeuroModulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Front Psychiatry. 2020 Mar 20;11:163. doi: 10.3389/fpsyt.2020.00163. eCollection 2020.
Susceptibility and resilience to mental disorders result from a complex choreography of gene-environment interactions with epigenetics at the intersection of external psychological stressors and internal biological systems. Increasing awareness of the growing disease burden influenced by daily life stress ("daily hassles"), work-related stress, and low socioeconomic status (SES) has resulted in a novel interest into their underlying molecular signatures. This review offers a brief outline of psychiatric epigenetics and a comprehensive overview of recent findings exploring the relationship of various occupational stressors and DNA methylation in epigenome-wide association studies (EWAS) and in candidate gene studies including the serotonin transporter (; LPR), melatonin receptor 1A (), brain-derived neurotrophic factor (), tyrosine hydroxylase (), and the protein family of DNA methyltransferases (). Conceptual and methodological challenges of epigenetic investigations with a special focus on gene-environment interactions are highlighted and discussed. The findings are integrated into a pathophysiological framework featuring epigenetic plasticity factors and work-related stress as a possible central detrimental component targetable by workplace interventions. Finally, the potential of dynamic epigenetic biomarkers of treatment response to pharmacotherapy or psychotherapy is expanded upon.
精神障碍的易感性和恢复力源于基因与环境在外部心理应激源和内部生物系统交叉点上通过表观遗传学进行的复杂相互作用。人们越来越意识到日常生活压力（“日常琐事”）、工作相关压力和低社会经济地位（SES）对疾病负担增长的影响，这引发了对其潜在分子特征的新兴趣。本综述简要概述了精神疾病表观遗传学，并全面综述了近期在全表观基因组关联研究（EWAS）以及候选基因研究（包括血清素转运体（；LPR）、褪黑素受体1A（）、脑源性神经营养因子（）、酪氨酸羟化酶（）以及DNA甲基转移酶蛋白家族（））中探索各种职业应激源与DNA甲基化关系的研究结果。文中强调并讨论了表观遗传学研究在概念和方法上的挑战，特别关注基因与环境的相互作用。研究结果被整合到一个病理生理框架中，该框架以表观遗传可塑性因素和工作相关压力作为工作场所干预可能针对的核心有害成分。最后，还阐述了治疗反应的动态表观遗传生物标志物在药物治疗或心理治疗中的潜力。
