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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.

Lahore, Anarkali, mid-1950s. A distinguished-looking refugee is standing in front of a petition writer in the hope of getting the better of the Pakistani bureaucracy and having a property allotted. A few miles ahead, another refugee, camped in a school, is drafting a letter to the editor of the Pakistan Times. He will hide his identity through the pseudonym ‘desperate'. Both of them belonged to the throng of those muhajirs who, back in 1947, had embarked on a dreadful journey towards what they perceived to be their homeland. Historiographical trends have tended to overlook the everyday experience of the state among those middle-class Partition refugees who resettled in Pakistani Punjab. Focusing mainly on their ‘less fortunate' fellow citizens, these explanations have reproduced that historically-unproven popular narrative that ascribes pain and sufferings only to the economically-backward sectors of the local society. Even more frequently, well-rooted argumentative patterns have superimposed historical and present-day socio-geographical mappings of refugee families onto both urban and rural Punjab. These somehow echo that government rhetoric that, up to the early 1960s, paid lip service to the notion of a ‘biraderi-friendly' rehabilitation. This thesis challenges standard interpretations of the resettlement of Partition refugees in Pakistani Punjab between 1947 and 1962. It argues the universality of the so-called ‘exercise in human misery', and the heterogeneity of the rehabilitation policies. As it sheds light on these latter original contributions to the current knowledge, it questions the ability of the local bureaucracy to establish its own ‘polity', the unsuitability of patronage political systems as an autonomous politological category, and the failure of Pakistan as a state. Individual chapters pursue questions of emotional belonging to spatial and political places, social change, everyday experiences of the state through its institutions, electoral politics, and the deployment of integration/accommodation practices as nation- and state-building processes.