Depression and adverse childhood experiences: Interplay between psychosocial, biological, and genetic factors across the life course

Student thesis: Doctoral ThesisDoctor of Philosophy


Adverse childhood experiences (ACEs), such as abuse and family dysfunction, are among the most potent psychosocial risk factors for depression. Stress-induced dysregulation of the hypothalamic-pituitary-adrenal (HPA)-axis and inflammatory systems might underlie the psychobiological impact of ACEs on depression. However, the evidence for the role of these biological mechanisms is weak owing to a limited availability of longitudinal data and other methodological issues. Furthermore, it remains unclear whether genetic influences could contribute to these relationships. This PhD consists of six studies seeking to elucidate the neuroendocrine, inflammatory, and gene-environment mechanisms through which ACEs might influence the risk of depression across the life course. Studies 1-4 focused on older adults, using data from the English Longitudinal Study of Ageing. Study 1 showed that older adults affected by ACEs exhibited chronically elevated systemic inflammation. In contrast, ACEs were unrelated to hair cortisol. Study 2 revealed that higher inflammation and cortisol levels were associated with persistent depressive symptoms over time. These relationships were stronger with somatic than with cognitive-affective symptoms. Study 3 demonstrated that ACEs were related to depression partly via elevated inflammation. Study 4 further showed that ACEs and polygenic susceptibility were independently and interactively associated with depression and inflammation. Studies 5-6 focused on young people, using data from the Twins Early Development Study and the Avon Longitudinal Study of Parents and Children. In Study 5, ACEs were associated with elevated depressive symptoms in young adulthood partly through lower salivary cortisol levels in adolescence, independently of genetic factors. Study 6 demonstrated that ACEs across different early-life periods (prenatal period, childhood, and adolescence) were associated with elevated depressive symptoms in young adulthood. In contrast, the associations of ACEs and depression with early-life inflammation were weak. These findings offer novel insights into the biological embedding of ACEs and can stimulate new mental health interventions.
Date of Award2021
Original languageEnglish
Awarding Institution
  • King's College London

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