Sex hormones and post-traumatic stress disorder (PTSD)

项目总结 美国未经治疗的创伤后应激障碍(PTSD)负担是导致 军事和民用部门的保健预算，以及更好的治疗和预防方法 需要的。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，创伤后应激障碍有一种隐藏的流行病。女性经历两次创伤后应激障碍 男性比例(11%比5%)，但这种性别差异的原因在很大程度上还不清楚。一直以来都是 怀疑性激素在该病的发生和潜在的保护作用中起着重要作用。 创伤后应激障碍和其他精神健康障碍。该项目将提供有史以来最大规模的性激素研究。 抑郁症和焦虑症对创伤后应激障碍及相关心理健康结局的影响鉴于 过去的研究受到样本量小的限制，结果不是决定性的，这次调查将使用 由大约500,000名参与者组成的大规模样本来回答关于两个广为人知的性行为的问题 激素(睾酮和雌二醇)和三种精神后果(创伤后应激障碍、抑郁和焦虑 紊乱)。这些变量是在英国生物库中测量的，我们已经获得了访问数据的权限 研究性激素对心理健康结果的影响，并研究两性之间潜在的遗传效应 荷尔蒙水平和精神健康障碍。这项工作的完成将揭示出脑力劳动的比率 健康障碍因睾酮和雌二醇水平不同而不同。情况可能是这样的，荷尔蒙水平 太高和太低都是有问题的。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线性和非线性关系 性激素与创伤后应激障碍、抑郁症和焦虑症之间的关系。样本量和研究设计 使这项研究成为迄今为止进行的最有力的研究，结果将可推广到不同的领域 人口。除了上述结果外，我们还将进一步探讨潜在的遗传效应 性激素与心理健康障碍的关系。为此，我们将在全基因组范围内进行 睾酮和雌二醇的联合研究(GWAS)。然后我们将为以下对象进行多基因评分 睾酮和雌二醇，产生性激素水平的遗传替代物，可用于 哪些性激素还没有被测量过。最后，我们将测试基因之间的共同遗传效应 为了更好地了解精神障碍的病因，性激素和遗传效应在精神障碍中的作用 这些常见的、令人衰弱的和没有得到充分治疗的精神健康疾病。这些加在一起， 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 用于治疗创伤后应激障碍、抑郁症和焦虑症的睾丸素和雌二醇。这些结果也将 为开发新的治疗和预防战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.