Childhood maltreatment and structural neuroanatomy as risk factors for adolescent onset depression

© 2012 Dr. Anna BarrettThis 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