The role of genes and environment in anxiety spectrum disorders

描述（由申请人提供）：焦虑症在人群中非常普遍，并带来严重的痛苦和损害。只有中等比例的焦虑症患者对目前的治疗有充分的反应，与其他精神综合征相比，焦虑症的研究相对不足。探索其遗传决定因素将有助于阐明其原因并指导预防和新治疗的研究。研究已经记录了遗传因素（可能与抑郁症和焦虑气质共同）和暴露于环境压力源在焦虑症发展中的作用。然而，大多数分子遗传学研究并没有在分析中考虑到这些因素。在这个项目中，我们将从全基因组关联分析中仔细选择10-15个候选焦虑障碍易感基因，并根据其他人类和啮齿动物遗传研究的证据进行加权。我们将在几个大型、独立的受试者样本中测试这些基因和环境风险因素（如童年逆境和压力生活事件）在焦虑谱表型中的作用的主要和相互作用。

DESCRIPTION (provided by applicant): Anxiety disorders are highly prevalent in the population and carry a significant burden of distress and impairment. Only a moderate proportion of patients with anxiety disorders respond adequately to current treatments, and anxiety disorders are relatively understudied compared to other psychiatric syndromes. Exploring their genetic determinants will help elucidate their causes and guide research for prevention and new treatments. Research has documented roles for both genetic factors, likely shared with depressive disorders and anxious temperament, and exposure to environmental stressors in the development of anxiety disorders. Yet most molecular genetic studies have not taken these factors into account in their analyses. In this project, we will carefully select 10-15 candidate anxiety disorder susceptibility genes from genome-wide association analyses weighted by evidence from other human and rodent genetic studies. We will test the main and interactive effects of these genes and environmental risk factors such as childhood adversity and stressful life events for their role in anxiety spectrum phenotypes in several large, independent samples of subjects. PUBLIC HEALTH RELEVANCE: The anxiety disorders are quite common, chronic, and disabling. Many patients with these conditions either poorly tolerate or do not adequately respond to standard treatments. Both genetic factors and exposure to environmental stress contribute to their development. The identification of the genes that play a role in their susceptibility will provide new clues to their causes and, hopefully, new directions for prevention and treatment research.