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

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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.