Psychiatry - Theses

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    Associations between early adversity, brain development, and mental health during adolescence
    Rakesh, Divyangana ( 2022)
    Early adverse experiences, like childhood maltreatment and socioeconomic disadvantage, are associated with lifelong consequences for mental health. However, the underlying neurobiological mechanisms of these associations are yet to be characterized. It has been suggested that adverse experiences may shape mental health via alterations in neurodevelopment. The aim of this thesis was to investigate how childhood maltreatment and socioeconomic disadvantage (which are both highly prevalent in the general community and are strong predictors of poor mental health outcomes), influence brain development during childhood and adolescence, and how those changes, in turn, contribute to mental health outcomes. An additional aim of the thesis was to examine environmental and psychological factors that may buffer the effects of adversity on brain development and mental health. This thesis used structural magnetic resonance imaging and resting state functional magnetic resonance imaging data from two studies, the Orygen Adolescent Development Study, and the Adolescent Brain Cognitive Development Study, in order to comprehensively characterize associations between childhood maltreatment, socioeconomic status (SES), and brain structure and functional connectivity as well as mental health. In the first and second study we investigated associations between childhood maltreatment (as well as specific dimensions of maltreatment) and longitudinal development of functional connectivity during adolescence, and showed that total maltreatment, abuse, and neglect, are associated with deviations in typical patterns of functional connectivity development. We also showed that these alterations in functional connectivity development are associated with mental health outcomes. Next, in the third study, we systematically synthesized the association between SES and brain structure, function, and connectivity, and showed that while there were some consistencies in findings, results were often mixed (especially at the level of individual SES indices). In the fourth and fifth study, we focused specifically on neighborhood disadvantage given that our review (third study) identified this to be a relatively unexplored SES indicator. In the fourth study, we showed that neighborhood disadvantage is associated with longitudinal alterations in brain-predicted-age trajectory, which was found to be moderated by temperamental effortful control. In the sixth study, we demonstrated cross-sectional alterations in functional connectivity as a function of disadvantage. We also showed that some of these alterations were associated with poor mental health. However, some associations between neighborhood disadvantage and functional connectivity were found to be moderated by positive parenting and favorable school environments. Finally, in studies six and seven, we demonstrate the independent and interactive effects of different SES indicators on brain structure and connectivity. We show that household income moderated the association between neighborhood disadvantage/low parent educational attainment and connectivity/brain structure. Overall, the findings of this thesis build knowledge around the impact of early adverse experiences on brain structure and functional connectivity, as well as mental health, during childhood and adolescence. Using whole-brain approaches, longitudinal data, and large samples, we were able to demonstrate that both childhood maltreatment and low SES are associated with widespread alterations in brain structure and function. These findings bring us one step closer to understanding the neurobiological pathways through which adversity ‘gets under the skin’ and impacts children’s mental health and wellbeing, and opens up exciting avenues for future research.