Identifikation of epigenetic and cerebral markers linking early life adversities and adult anxiety disorder

识别早期生活逆境和成年焦虑症之间的表观遗传和大脑标记

• 批准号: 298908449
• 负责人: Professor Dr. Andreas Jochen Fallgatter
• 金额: --
• 依托单位: Universitätsklinik für Psychiatrie und Psychotherapie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/298908449?language=en
• 关键词: Identifikation; epigenetic; cerebral; markers; linking

Anxiety disorders are the most common group of mental disorders with a twelve-month prevalence of 14% in the European population. The aetiology of anxiety is influenced by genetic (heritability estimates: 30 - 68%) as well as environmental factors. The contribution of early life adversities to pathopysiological processes which lead to an increased risk for anxiety disorders later in life has been consistently described, but the underlying biological mechanisms are still poorly understood. Evidence is emerging, that epigenetic processes might play a role in the physiological responses linking early life adversities and anxiety disorders. It has been demonstrated that both, anxiety disorders and early life adversities, are associated with distinct alterations of the brain. In contrast to numerous genetic imaging studies performed to date, the influence of epigenetic processes on cerebral connectivity as well as activation patterns and more importantly their potential mediating function between early life adversities and the occurrence of anxiety disorders remains to be elucidated. The aims of the proposed research project are therefore to i) identify peripheral epigenetic biomarkers which could predict the occurrence of anxiety disorders in individuals previously subjected to early life adversities and to ii) evaluate the cerebral correlates of epigenetic influences of early life adversities on the occurrence of anxiety disorders and their potential function as mediators between epigenetic biomarkers and anxiety disorders. We intend to investigate early life adversity-responsive genes in a large cross-sectional cohort of adult anxiety disorder patients and healthy control individuals to identify whether those genes qualify as epigenetic biomarkers of anxiety disorders. Furthermore, in an imaging epigenetics approach, we aim to investigate the influence of the epigenetic regulation of those genes on brain properties to localize cerebral mediators of epigenetic-driven effects of early life adversities on the development of anxiety disorders. The current approach will lead to a better understanding of the neurobiological mechanisms leading from early life adversities to adult anxiety disorders. Moreover, deeper insights into the epigenetic regulation of anxiety disorders could open new avenues in diagnoses, treatment, and prevention and a panel of peripheral biomarkers could be used to identify individuals at risk for anxiety disorders early after the exposure to early life adversities which in turn might contribute to the prevention of disease onset as protective strategies could be applied promptly.

焦虑症是最常见的精神障碍，在欧洲人群中的12个月患病率为14%。焦虑的病因学受遗传（遗传率估计：30 - 68%）和环境因素的影响。早期生活逆境对病理生理过程的贡献导致晚年焦虑症的风险增加，这一点一直被描述，但其潜在的生物学机制仍然知之甚少。有证据表明，表观遗传过程可能在连接早期生活逆境和焦虑症的生理反应中发挥作用。已经证明，焦虑症和早期生活逆境都与大脑的不同变化有关。与迄今为止进行的众多遗传成像研究相反，表观遗传过程对大脑连接以及激活模式的影响，更重要的是其在早期生活逆境和焦虑症发生之间的潜在介导功能仍有待阐明。因此，拟议的研究项目的目的是i）确定外周表观遗传生物标志物，可以预测早期生活逆境的个体中焦虑症的发生，以及ii）评估早期生活逆境对焦虑症发生的表观遗传影响的大脑相关性及其作为表观遗传生物标志物和焦虑症之间的中介的潜在功能。我们打算在一个大型的成人焦虑症患者和健康对照人群的横断面队列中研究早期生活中的不良反应基因，以确定这些基因是否有资格作为焦虑症的表观遗传生物标志物。此外，在成像表观遗传学方法中，我们的目标是研究这些基因的表观遗传调节对大脑特性的影响，以定位早期生活逆境对焦虑症发展的表观遗传驱动影响的大脑介质。目前的方法将导致更好地理解从早期生活逆境到成人焦虑症的神经生物学机制。此外，更深入地了解焦虑症的表观遗传调控可以为诊断，治疗和预防开辟新的途径，并且一组外周生物标志物可以用于在暴露于早期生活逆境后早期识别处于焦虑症风险中的个体，这反过来可能有助于预防疾病发作，因为可以及时应用保护策略。