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，在平民和妇女中有一种隐藏的创伤后应激障碍流行病。女性经历创伤后应激障碍的几率 男性的比例（11%对5%），但这种性别差异的原因在很大程度上尚不清楚。人们早就 怀疑性激素在发展中起着重要作用--也可能是保护-- PTSD和其他心理健康障碍。该项目将提供有史以来最大的性激素研究 对创伤后应激障碍以及抑郁症和焦虑症的相关心理健康结果的影响。而 过去的研究受样本量小的限制，结果不确定，本次调查将使用 一个大约50万参与者的大规模样本，回答关于两个众所周知的性别的问题， 激素（睾酮和雌二醇）和三种精神疾病（创伤后应激障碍、抑郁和焦虑 疾病）。这些变量是在英国生物银行测量的，我们已经被授权访问数据 研究性激素对心理健康结果的影响， 激素水平和精神疾病。这项工作的完成将揭示精神疾病的发病率 健康障碍随着睾酮和雌二醇水平的变化而变化。这可能是因为荷尔蒙的水平 太高和太低都是有问题的。考虑到这一现实，我们将使用复杂的回归， 机器学习技术，因此我们将能够检测线性和非线性关系， 性激素和创伤后应激障碍抑郁症和焦虑症之间的联系样本量和研究设计 这是迄今为止进行的最有力的研究，结果将推广到各种各样的人。 人口数量。除了上述结果外，我们还将进一步探讨遗传效应的潜在影响。 性激素和精神疾病之间的关系为了做到这一点，我们将进行全基因组 睾酮和雌二醇的相关性研究（GWAS）。然后我们将对 睾酮和雌二醇，产生性激素水平的遗传代理，可用于研究 哪些性激素还没有被测量过最后，我们将测试遗传基因之间的共享遗传效应。 对性激素的影响和对精神疾病的遗传影响，以便更好地了解病因 这些常见的，使人衰弱的，治疗不足的心理健康疾病。综上所述各项 研究结果将提供与目前正在测试的临床试验相关的关键基础知识 睾酮和雌二醇用于治疗创伤后应激障碍、抑郁症和焦虑症。这些结果也将 为开发新的治疗和预防策略提供可操作的发现。

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.