Sex hormones and post-traumatic stress disorder (PTSD)

项目摘要 在美国，未经治疗的创伤后应激障碍（PTSD）负担是导致 军事和民用部门的医疗保健预算，以及更好的治疗和预防方法， needed.幸运的是，近年来军人对创伤后应激障碍的认识有所提高，然而， 创伤后应激障碍在平民和妇女中有着隐蔽的流行。女性经历创伤后应激障碍的几率是男性的两倍。 男性的比例（11%对5%），但这种性别差异的原因在很大程度上是未知的。人们一直怀疑 性激素在创伤后应激障碍和其他疾病的发展中起着重要作用， 心理健康障碍该项目将提供有史以来最大的性激素对创伤后应激障碍的影响的研究， 抑郁症和焦虑症的相关心理健康结果。而过去的研究 由于样本量小且结果不确定，本研究将使用 约500，000名参与者回答有关两种众所周知的性激素（睾酮和 雌二醇）和三种精神疾病（创伤后应激障碍、抑郁症和焦虑症）。这些变量 在英国生物银行测量，我们已经获准访问数据，研究性激素的影响， 研究性激素水平和心理健康的遗传效应 紊乱这项工作的完成将揭示精神健康障碍的发生率是否随睾丸激素的变化而变化。 和雌二醇水平。这可能是这样的情况下，激素水平过高和过低， 有问题鉴于这一现实，我们将使用复杂的回归和机器学习技术， 因此，我们将能够检测性激素和创伤后应激障碍之间的线性和非线性关系， 抑郁症和焦虑症。样本量和研究设计使其成为最强大的研究 迄今为止进行的研究，其结果将推广到不同的人群。除了结果之外， 如上所述，我们将进一步探讨性激素和 心理健康障碍为了做到这一点，我们将进行全基因组关联研究（GWAS）， 睾酮和雌二醇。然后，我们将对睾酮和雌二醇进行多基因评分， 性激素水平的替代物，可用于未测量性激素的研究。 最后，我们将测试遗传对性激素的影响和遗传对 精神疾病，以更好地了解这些常见的，衰弱的，不充分的病因， 治疗精神疾病综合起来，这些发现将提供关键的基础知识， 与目前测试睾酮和雌二醇治疗创伤后应激障碍的临床试验相关， 抑郁症和焦虑症。这些结果还将为制定 新的治疗和预防策略。

Project Summary The untreated burden of post-traumatic stress disorder (PTSD) in the United States is a massive contributor to healthcare budgets in both the military and civilian sectors, and better treatment and prevention methods are needed. Fortunately, awareness of PTSD among military service members has grown in recent years, and yet, there is a hidden epidemic of PTSD among civilians and women. Women experience PTSD at about twice the rate of men (11% vs. 5%), but the causes for this sex difference are largely unknown. It has long been suspected that sex hormones play a major role in development of – and also potentially protection from – PTSD and other mental health disorders. This project will provide the largest ever study of sex hormone effects on PTSD and the related mental health outcomes of depression and anxiety disorders. Whereas studies in the past were limited by small sample sizes and results were inconclusive, this investigation will use a massive sample size of approximately 500,000 participants to answer questions about two well-known sex hormones (testosterone and estradiol) and three psychiatric outcomes (PTSD, depression, and anxiety disorders). These variables were measured in the UK Biobank, and we have been granted access to the data to study sex hormone effects on mental health outcomes and to study genetic effects underlying both sex hormone levels and mental health disorders. The completion of this work will reveal whether rates of mental health disorders vary with testosterone and estradiol levels. It may be the case that levels of hormones that are both too high and too low are problematic. Given this reality, we will use sophisticated regression and machine learning techniques, and therefore we will be able to detect linear and non-linear relationships between sex hormones and PTSD, depression, and anxiety disorders. The sample size and study design make this the most powerful study conducted to date, and the results will be generalizable to diverse populations. In addition to the outcomes mentioned above, we will further explore genetic effects underlying relationships between sex hormones and mental health disorders. To do this, we will conduct genome-wide association studies (GWAS) of both testosterone and estradiol. We will then make polygenic scores for testosterone and estradiol, yielding genetic proxies of sex hormone levels which can be used in studies in which sex hormones have not been measured. Finally, we will test for shared genetic effects between genetic effects on sex hormones and genetic effects on psychiatric disorders in order to better understand the etiology of these common, debilitating, and inadequately treated mental health disorders. Taken together, these findings will provide critical foundational knowledge relevant to clinical trials which are currently testing testosterone and estradiol as treatments for PTSD, depression, and anxiety disorders. These results will also provide actionable findings for the development of novel treatment and prevention strategies.