Maternal separation in childhood and the role of biomarkers of stress in its association with mental and physical health

这一博士学位的主要重点是调查早期生活事件影响成年后身心健康结果的机制。关于这一主题的研究已经有了很长的历史，研究表明童年不良事件与后来生活的一系列结果之间存在显著的关联，包括心血管疾病(Su等人，2015；Anderson等人，2018)和抑郁症(Poole等人，2017；刘，2017)。这两种情况不仅对个人的生活，而且对整个社会都有重大影响。根据最新的全球疾病负担(GBD，2016)研究，心血管疾病估计导致全球1760万人死亡，是全球头号死因。同样，在世界卫生组织(WHO，2017)最近的一份报告中，抑郁症被报告为残疾的主要原因，估计全球患病率为4.4%。鉴于早期生活事件对这些情况的强烈影响，有必要了解这种关系中涉及的潜在机制，以应对这些全球健康风险。目标1：调查儿童时期母亲分离对成人身心健康结果的影响，并检查皮质醇在这种关系中的潜在中介作用。母亲分离和皮质醇之间的关系是否直接影响，还是受到分离发生后的行为和社会因素的影响？母亲分离对成年人身心健康结果的影响是否因性别而异？目标2：在白厅II中调查唾液皮质醇与抑郁症无关的原因。我计划在迄今为止讨论的我的博士学位的每个组成部分中使用的主要数据来源将来自白厅II的研究。这是一项始于1985年的英国纵向研究，收集了10308名受雇于伦敦公务员办公室的英国公务员的数据(Marmot&Brunner，2005年)。从那时起，这项研究又收集了11个阶段的数据。怀特霍尔II研究特别适合于调查这个项目的研究目的和目的，原因有很多。首先，它包含了关于儿童早期事件的信息，包括母亲分离。与其他一些大型调查相比，儿童事件的总体数量相对较低。然而，在其他调查中很少发现关于长期产妇分居的措施。其次，它包含了许多贯穿成人生活过程的心理社会和社会经济措施。为了建立足够的途径模型并解决AIMS中讨论的研究问题，这些措施将是必要的。AIMS试图确定儿童时期母亲离异对成年皮质醇水平的影响是直接的，还是由分居期之后发生的社会和行为因素调节的。最后，白厅II研究包含了广泛的临床措施和事件。这包括两种皮质醇：头发和唾液。前者在第十一阶段(2012-13年)测量了一次，但后者在第七阶段(2002-2004年)和第九阶段(2007-2009年)两次不同的场合进行了测量。这项研究还衡量了抑郁症，并包含了心血管死亡率的记录。因此，现有的数据衡量标准将使我能够调查上文部分概述的每一项目的和目标。

The primary focus of this PhD is to investigate the mechanisms through which early life events impact physical and mental health outcomes in adulthood. Research on this topic has a long history and studies have shown significant associations between adverse childhood events and a range of outcomes in later life, including cardiovascular disease (Su et al, 2015; Anderson et al, 2018) and depression (Poole et al, 2017; Liu, 2017). Both of these conditions have a significant impact not only upon the lives of individuals, but society as a whole. According to the latest Global Burden of Disease (GBD, 2016) study, cardiovascular disease was estimated to be responsible for 17.6 million deaths worldwide and is the global number one cause of death. Similarly, in a recent report by the World Health Organisation (WHO, 2017), depression was reported as the leading cause of disability with an estimated global prevalence rate of 4.4%. Given the strong influence that early life events can have on these conditions, an understanding of the underlying mechanisms involved in this relationship is necessary to tackle these global health risks.Aim 1: To investigate the impact of maternal separation in childhood on adult physical and mental health outcomes, and examine the potential mediating role of cortisol in this relation.Is the relationship between maternal separation and cortisol a direct effect, or is it influenced by behavioural and social factors following the occurrence of separation?Does the effect of maternal separation on adult physical and mental health outcomes vary by sex?Aim 2: To investigate the reasons why salivary cortisol is not associated with depression in Whitehall II.The primary data source that I will plan to use in every component of my PhD that has been discussed so far will come from the Whitehall II study. This is a British longitudinal study that began in 1985, collecting data on 10308 British Civil Servants employed in London based civil service offices (Marmot & Brunner, 2005). Since then, the study has collected a further eleven phases of data. The Whitehall II study is particularly suited to investigating the research aims and objectives of this project for a number of reasons.To begin with, it contains information on early childhood events, including maternal separation. The overall amount of childhood events is relatively lower than some other large-scale surveys. However, measures on long term maternal separation are rarely found in other surveys. Secondly, it contains numerous psychosocial and socioeconomic measures across the adult life course. Such measures will be necessary in order to carry out sufficient pathway models and to address the research question discussed in the aims, which tries to determine whether the effect of maternal separation in childhood on adult cortisol levels is direct, or whether it is mediated by social and behavioural factors that occur after the period of separation. Finally, the Whitehall II study contains an extensive range of clinical measures and events. This includes two measures of cortisol; hair and salivary. The former was measured once in phase eleven (2012-13), but the latter is measured on two different occasions at phase seven (2002-2004) and phase nine (2007-2009). The study also measures depression and contains records on cardiovascular mortality. As a result, the available data measures will allow me to investigate each of the aims and objectives outlined in the section above.