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

点击翻译按钮获取中文摘要

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.