Melbourne School of Psychological Sciences - Theses
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ItemThe role of candidate gene x environment interactions in eating pathology: an investigation of the 5-HTTLPR polymorphism( 2017)The present thesis with publication aimed to clarify current scientific understanding of candidate gene x environment (GxE) interactions in the eating disorder (ED) field, and to build upon existing findings through specific investigation of adolescent disordered eating and the 5-HTTLPR polymorphism. Study 1 involved a systematic review of published studies of GxE interactions involving 5-HTTLPR in the ED field, followed by four meta-analyses involving the combination of raw data from the original studies. From the four analyses undertaken (investigating the environmental variables traumatic life events, N = 909, sexual and/or physical abuse, N = 1,097, and the psychological variables depression, N = 1,254, and impulsivity, N = 1,122), results supported moderation by 5-HTTLPR in the relationship between sexual and physical abuse and bulimic spectrum pathology, with some support for moderation by 5-HTTLPR in the relationship between traumatic life events and overall EDs. No interactions between 5-HTTLPR and psychological factors were identified. Study 2 aimed to conceptually replicate these results in a large, independent sample drawn from the Australian Temperament Project (N = 650). Results showed no interaction between 5-HTTLPR and psychological factors (depressed mood or emotional control), but revealed a severity-dependent effect whereby there was some evidence of moderation by 5-HTTLPR in the relationship between severe, but not moderate-to-mild, parental physical punishment and adolescent EDI-2 Bulimia scores. The final investigation, Study 3, examined potential direct effects and GxE interactions between parenting and 5-HTTLPR to predict disordered eating from a ‘plasticity’ perspective, across two samples. Study 3a found an association between self-reported parental warmth and lowered EDI-2 Bulimia scores, and between self-reported parental use of physical punishment and greater EDI-2 Drive for Thinness scores (N = 650), however no moderation by 5-HTTLPR was identified. Study 3b aimed to replicate these findings using an observational measure of parenting behaviours, and constituted the largest study of observed parenting behaviours in the ED field (N = 304), as well as the first GxE interaction study in the field to include observational measurement of parenting behaviours. Results showed an association between parental warmth and lower EDI-2 Drive for Thinness scores, but no association between parental hostility and disordered eating, or any GxE interactions. Overall, results across the three studies of the present thesis supported moderation by 5-HTTLPR in the relationship between severe environmental stressors and eating pathology, but not between less severe environmental factors or psychological factors and ED outcomes. These results illustrate the important role of genetic factors in ED aetiology, carry implications for understanding the individual differences in response to potential environmental risk factors for EDs, and can be used to help inform ED prevention initiatives. Outstanding issues in investigation of candidate gene research in the ED field include sample size, publication bias, and multiple testing. Continued collaboration to increase sample sizes and careful selection of environmental and psychological measures is recommend for future GxE investigations, along with a move towards polygenic and genome wide investigative approaches.
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ItemChildhood maltreatment and structural neuroanatomy as risk factors for adolescent onset depression( 2012)This thesis concerns three broad subjects – childhood maltreatment, structural neuroanatomical features in early adolescence, and depressive symptoms in mid-adolescence – with the aim of examining predictive relationships between them. The core focus of the thesis was on investigating relationships between the volumes of key brain structures implicated in emotion regulation, and adolescent onset depression. The measurement of brain structures in a psychiatrically healthy sample of children aged 11-12 years, and the use of these measurements to predict onset of depressive symptoms 2-3 years later, allowed for contribution to theoretical debate about the timing of structural alterations previously associated with depression – specifically, whether observed alterations formed risk factors for depression, or whether they were outcomes of disease-related processes. The evidence of premorbid structural alterations demonstrated by this thesis suggests that there are vulnerability biomarkers for depression, and may assist in better understanding the mechanisms of depressive illness as well as identifying individuals at risk. The secondary focus of the thesis was on retrospectively examining relationships between maltreatment in childhood and structural neuroanatomical features in adolescence, with the aim of identifying effects of childhood adverse experience on brain development. Previous studies have largely utilised adult populations with maltreatment-related psychiatric illness, and therefore have not been able to conclude whether structural alterations following childhood maltreatment only occur in those individuals who later develop psychopathology, or whether these changes occur before the onset of any psychopathology. This thesis investigated whether structural changes were associated with childhood maltreatment in a healthy sample of young adolescents, allowing the separation of early experiential effects from later psychopathological processes. This research also explored whether the volumes of selected brain structures mediated relationships between childhood maltreatment and adolescent onset depression, however no such relationships were detected. As this was an exploratory measure secondary to the key themes of the thesis, and interpretations were constrained by issues of sample size, it is not dealt with in detail. The most robust aspect of this research design was the examination of neurostructural risk factors for depression, and this formed the central content of the thesis. There is also a large extant body of research and literature on depression and brain development, from which to gain a strong theoretical grounding on the role of each brain structure examined in terms of the cognitive and affective processes it is thought to subserve. For this reason, material on the epidemiology and neurobiological models of depression form the first three chapters. An exploration of the emerging body of literature on the relationships between childhood maltreatment and brain development is contained subsequently. Chapter 1 provides an introduction to the epidemiology and selected etiological influences on adolescent depression. Chapter 2 gives an overview of the current understanding of brain development in adolescence, and describes some of the key theoretical models linking brain development to adolescent onset depression. Key structures highlighted in these models were selected for investigation within this thesis, and detailed examination of the evidence and resultant hypotheses for each of five selected structures’ relationships with depression is contained in Chapter 3. The focus then turns to childhood maltreatment as a second major contributor to adolescent onset depression; Chapter 4 summarises research on the prevalence and types of childhood maltreatment and the relationships between childhood maltreatment and adverse outcomes including the development of depression. Chapter 5 reviews literature from the emerging field of developmental traumatology, drawing inferences from the body of work examining neuroendocrinological sequelae of childhood maltreatment and bringing together preliminary findings from a range of sources to form hypotheses regarding potential relationships between childhood maltreatment and the brain structures discussed in previous chapters. Chapter 6 gives detail on the design and methodology of the thesis, and Chapter 7 explains the data analysis used and reports on the results. Interpretation of findings, discussion of strengths and limitations of the research, and implications for future work are contained in Chapter 8.