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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ItemEnvironment-by-brain development interactions as predictors of adolescent depressive symptoms and psychological well-being: structural brain development as a marker of responsivity to maternal parenting and socioeconomic status( 2019)Background Adolescence is widely reported to be a time of increased risk for depression and lower well-being. Importantly, however, outcomes are heterogeneous, and most adolescents do not develop mental health problems. In order to understand how these differences emerge, both environmental and biological factors have been examined in the literature. Evidence indicates that parenting behaviour, socioeconomic status and neurobiology may contribute and, further, that individual differences in brain development may moderate the extent to which contextual factors influence adolescents. That is, individual differences in brain development may confer ‘responsivity’ to context. Several developmental and evolutionary-developmental models provide frameworks with which to interpret such brain-by-environment interactions, and to describe biological responsivity – these are broadly associated with diathesis-stress and differential susceptibility/biological sensitivity frameworks. Broad PhD aim This thesis aims to investigate whether structural brain development moderates adolescent sensitivity to maternal parenting behaviour in the prediction of adolescent depressive symptoms and psychological well-being. Two empirical studies were completed to address this aim. Study 1 examined whether longitudinal change in brain structure modified adolescent vulnerability or susceptibility to aggressive and positive maternal parenting. Effects were assessed to infer evidence in support of either diathesis-stress or differential susceptibility frameworks. Study 2, in light of evidence that positive parenting protects against adversity, considered whether brain development moderated adolescent sensitivity to positive parenting, and whether this association was more pronounced for adolescents with low-socioeconomic status (SES). Methodology During early adolescence (age 13 years), participants completed observed interactions with their mothers, and the frequency of positive maternal behaviour was coded. At three time points (mean ages 13, 17 and 19 years), participants completed structural magnetic resonance imaging (MRI) scans. During late adolescence (age 19 years), participants completed self-report measures of depressive symptoms and psychological well-being. Two separate analyses (studies) were conducted in predicting late adolescent (age 19) outcomes (depressive symptoms and psychological well-being). For both studies, longitudinal brain development was indexed by changes in cortical thickness of structures within the frontal lobe, and volumetric changes of subcortical structures, from early to late adolescence. Study 1: Regression models analysed interactions between maternal behaviour and longitudinal brain development in the prediction of adolescent outcomes. Indices designed to distinguish between diathesis-stress and differential susceptibility effects were employed. Study 2: Regression models were used to investigate interactions between SES (parental occupation), positive maternal behaviour, and longitudinal brain development in the prediction of adolescent outcomes. Results Study 1: Results supported differential susceptibility, whereby less thinning of frontal regions (the left medial orbitofrontal, rostral middle frontal and superior frontal cortices, and the right pars opercularis) was associated with higher well-being in the context of low levels of aggressive maternal behaviour, and lower well-being in the context of high levels of aggressive maternal behaviour. Study 2: Results indicated that individual differences in structural brain development moderated the extent to which positive parenting impacted adolescents dependent on SES. High levels of positive parenting were associated with reduced depressive symptoms for low-SES adolescents with greater volumetric reduction of the right putamen. Further, low positive parenting was associated with reduced psychological well-being for individuals with greater neurobiological sensitivity, however, patterns of brain development that were associated with sensitivity differed by SES. Specifically, low positive parenting was associated with reduced psychological well-being for individuals with more thinning in the context of low-SES, but for individuals with less thinning in the context of high-SES. Significance Results across studies suggested that structural brain development may be associated with individual differences in how sensitive adolescents are to context. Study 1 indicated that reduced frontal cortical thinning during adolescence increased susceptibility to maternal aggressive behaviour in the prediction of well-being, for better and for worse. This finding is significant because it suggests that neither more or less cortical thinning is consistently good or bad for mental health. Results from Study 2 indicated that, although brain change was associated with responsivity to parenting behaviour, patterns of brain development associated with heightened responsivity to parenting were different for high- and low-SES. These results suggested that responsivity functions in a context dependent fashion and highlights the complex interactions that may occur across biological and multilevel environment factors. Results from these studies suggest that structural brain development may be a marker of responsivity to environmental influence. They also emphasise the importance of examining how brain development moderates the impact of multilevel environmental factors on mental health outcomes. Such study designs may better reflect the social settings in which adolescents develop.