Psychiatry - Theses
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ItemCharacterising relationships between adolescent sleep, brain development and psychopathology( 2023-07)Background. Sleep is critical for cognitive, emotional, behavioural and physiological wellbeing, particularly during the adolescent period. Adolescents experience substantial changes in sleep behaviour, such as delays in timing, decreases in duration, changes in sleep staging and sleep-related preferences. When combined with external psychosocial demands, however, such changes often result in sleep that is chronically insufficient and of poor quality. While the relationship between poor and insufficient sleep and psychopathology is well established, little is known about the role of changes in sleep on long-term mental health outcomes. Further, little work has accounted for the comorbidity of sleep behaviours, and especially the role of comorbid sleep problems, when examining relationships between sleep and psychopathology. In addition, cross-sectional evidence suggests that relationships between sleep and psychopathology may be anchored or mediated by changes in brain structure, and substantial evidence from preclinical studies suggests insufficient and poor sleep may negatively impact the developing brain. However, little prospective work has investigated this hypothesis in humans. The general aim of this thesis was to characterise longitudinal relationships between sleep, psychopathology and brain development across adolescence. Methods. Subjective questionnaires of sleep behaviour and psychopathology, combined with structural magnetic resonance imaging data from two longitudinal studies, was used to examine prospective relationships between sleep, psychopathology and brain structure and development across adolescence. Results. In our first study, we showed that diurnal preference, a sleep-related behaviour that indexes an individual’s preferred timing of sleep, underwent non-linear delays during adolescence. This delay resulted in an overall increase in eveningness preference across the entire sample. In turn, individuals with a greater shift towards eveningness were more likely to experience externalizing psychopathology symptoms, and also evinced an attenuated trajectory of white matter development in late adolescence. In our second study, we observed substantial diversity in the types and patterns of sleep problems experienced by pre-adolescents, which further diversified in the transition into young adolescence. Changes in sleep problems over time were in turn associated with significant changes in psychopathology. In the third study, we identified associations between brain structure, insomnia and psychopathology symptoms, and that these associations showed significant overlap cross-sectionally and prospectively, indicating that similar neural regions are associated with both insomnia and psychopathology. Conclusions. This thesis demonstrates that sleep, psychopathology and brain structure and development are tightly interconnected. Sleep- and sleep-related behaviours were found to predict changes in psychopathology, and may also influence brain development and structure. Further, structural alterations associated with specific sleep behaviours are shared with psychopathology, which may indicate shared neurobiological mechanisms underpinning their established comorbidity. Taken together, findings from this thesis provide further evidence for the critical importance of sleep for adolescent mental health, and also suggest that sleep may also be important for optimal brain development.
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ItemAssociations between early adversity, brain development, and mental health during adolescence( 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.