TEDS 26: A longitudinal genetic approach to understanding the development and intergenerational transmission of common mental health conditions

我们年轻人抑郁和焦虑的统计数据令人震惊。超过三分之一的人经历过这些情况，而且比率正在上升，特别是在年轻女性中。焦虑和抑郁症是高度衰弱，扰乱教育，降低正常的工作能力，并显着增加自杀风险。尽管如此，每人每年花费不到2英镑用于研究了解它们。焦虑和抑郁与身体健康状况也有非常复杂的关系，越来越多的证据表明存在双向影响，以及具有特定身体健康状况的抑郁症亚型。这种复杂的情况由于仍然围绕着这些疾病的耻辱而变得更加糟糕，因此许多人不寻求帮助，或者即使他们这样做，他们也是出于身体而不是心理上的担忧。这种背景意味着我们对焦虑和抑郁如何发展的了解远远少于我们需要的，谁是最危险的，这些条件何时以及如何影响身体健康问题，以及哪些因素推动寻求治疗和更多的一般卫生服务使用。此外，尽管几个世纪以来我们都知道焦虑和抑郁“在家庭中运行”，但我们对哪些因素导致患有焦虑或抑郁的父母的孩子自己发展这种状况知之甚少。这个问题对许多经历焦虑和抑郁的年轻人至关重要。我们的总体目标是改变我们预测谁在20多岁时有焦虑和/或抑郁风险的能力，以及我们对相关特征如何从一代传递到下一代的理解。我们的研究结果将使我们能够具体说明谁和何时进行干预，以破坏这些条件的发展和代际循环。为了实现这一目标，我们将与双胞胎早期发展研究（TEDS）的参与者进行三组新的数据收集。TEDS从1994年至1996年在英格兰和威尔士出生的双胞胎出生时就开始跟踪，评估了一系列广泛的情感，行为，认知和语言措施。全基因组遗传数据也可获得。大约有10，000个家庭仍然活跃在研究中，其中约65%的家庭在每一波数据收集中都做出了一致的回应。当他们接近25岁时，双胞胎开始生孩子，这为他们和他们的后代提供了一个令人兴奋和独特的机会。首先，我们将在26岁时使用在线评估收集有关当前心理健康状况的信息。这将使我们能够利用所有先前的信息来建立模型，以确定在成年早期发展心理健康状况的风险最大的群体，这些群体可以从早期预防工作中受益。其次，我们将把TEDS双胞胎的常规医疗记录信息与我们的数据集连接起来，这些数据集是在25年的时间里建立起来的。这将提供额外的外部独立信息，包括关于心理健康状况、身体健康状况和医疗服务使用情况的信息，所有这些信息都有助于完善风险模型。第三，我们将招募和评估TEDS参与者的子女，这将允许在基因和环境的相对贡献之外估计父母对子女和子女对父母的影响。我们将利用这项工作来推动新一波的预防试验，建立在我们设计的风险模型基础上。此外，我们将继续鼓励国际研究人员访问TEDS数据资源，以解决我们核心关注范围以外的问题。

The statistics for depression and anxiety in our young people are shocking. Over one-third experience these conditions and rates are rising, particularly in young women. Anxiety and depressive disorders are highly debilitating, disrupt education, reduce normal work capacity and dramatically increase suicide risk. Despite this, <£2 is spent per person per year on research into understanding them. Anxiety and depression also have very complex relationships with physical health conditions, with growing evidence for bidirectional effects, and putative sub-types of depression with specific physical health profiles. This complex picture is made even worse by the stigma which still surrounds these conditions, so many people do not seek help, or if they do, they do so for physical rather than psychological concerns. This backdrop means we know much less than we need to about how anxiety and depression develop, who is most at risk, when and how these conditions influence and are influenced by physical health concerns, and which factors drive treatment seeking and more general health service use. Furthermore, despite having known for centuries that anxiety and depression "run in families" we know very little about which factors lead to the child of a parent with anxiety or depression developing that condition themselves. This question is of key importance to many young people experiencing anxiety and depression.Our overarching aim is to transform our ability to predict who is at risk of anxiety and/or depression in their mid-twenties and our understanding of how related traits are transmitted from one generation to the next. Our findings will allow us to specify for whom and when to intervene to disrupt the development and intergenerational cycle of these conditions. To address this aim, we will undertake three sets of new data collection with participants of the Twins Early Development Study (TEDS). TEDS has followed twins born in England and Wales in 1994-1996 from birth, assessing a wide array of emotional, behavioural, cognitive and language measures. Genome-wide genetic data are also available. Approximately 10,000 families are still active in the study, of whom ~65% consistently respond at each wave of data collection. As they approach their mid-twenties the twins are starting to have children, providing an exciting and unique opportunity to re-engage them and their offspring. First, we will collect information about current mental health conditions using online assessment at age 26. This will allow us to utilise all our prior information to build models that identify groups at the greatest risk of developing mental health conditions in young adulthood, who could benefit from early prevention efforts. Second, we will connect information from TEDS twins' routine medical records to our dataset, built up over 25 years. This will offer additional external, independent information, including on mental health conditions, physical health conditions and use of medical services, all of which can help refine models of risk. Third, we will recruit and assess the children of TEDS participants, which will allow estimation, beyond the relative contributions of genes and environment, of parent-to-child and child-to-parent effects. We will use this work to drive a new wave of prevention trials, built on the risk models we devise. Furthermore, we will continue to encourage researchers internationally to access the TEDS data resource to address questions beyond our core focus.