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

本博士的主要重点是研究通过早期生活事件影响成年期身心健康结果的机制。关于这一主题的研究历史悠久，研究表明童年不良事件与晚年一系列结果之间存在显著关联，包括心血管疾病（Su et al, 2015; Anderson et al, 2018）和抑郁症（Poole et al, 2017; Liu, 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，心血管疾病估计在全球造成1760万人死亡，是全球头号死亡原因。同样，在世界卫生组织最近的一份报告中（世卫组织，2017年），抑郁症被报告为导致残疾的主要原因，估计全球患病率为4.4%。鉴于早期生活事件可能对这些疾病产生强烈影响，了解这种关系所涉及的潜在机制对于解决这些全球健康风险是必要的。目的1：探讨童年母亲分离对成人身心健康结果的影响，并探讨皮质醇在这一关系中的潜在中介作用。母亲分离与皮质醇的关系是直接作用，还是受到分离发生后的行为和社会因素的影响？母亲分离对成人身心健康结果的影响是否因性别而异？目的2：探讨唾液皮质醇与白厅II期抑郁症无关的原因。到目前为止，我计划在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研究。这是一项始于1985年的英国纵向研究，收集了10308名在伦敦公务员办公室工作的英国公务员的数据（Marmot & Brunner, 2005）。从那时起，这项研究又收集了11个阶段的数据。白厅二期研究特别适合于调查这个项目的研究目的和目标，原因有很多。首先，它包含关于幼儿期事件的信息，包括母亲分离。与其他一些大规模调查相比，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离的措施。其次，它包含了贯穿整个成人生活过程的许多社会心理和社会经济措施。这些措施将是必要的，以便进行足够的途径模型，并解决在目标中讨论的研究问题，该研究试图确定童年时母亲分离对成人皮质醇水平的影响是直接的，还是由分离期后发生的社会和行为因素介导。最后，白厅II研究包含了广泛的临床测量和事件。这包括对皮质醇的两种测量；头发和唾液。前者在第11阶段（2012-13）测量一次，而后者在第7阶段（2002-2004）和第9阶段（2007-2009）分别测量两次。该研究还测量了抑郁症，并包含心血管疾病死亡率的记录。因此，可用的数据措施将使我能够调查上面一节中概述的每个目的和目标。

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.