Melbourne School of Psychological Sciences - Theses
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ItemAdolescent-onset depression: the interplay between family relationships, brain development and inflammation( 2014)Adolescence is an important life phase in which to explore psychological functioning. The emergence of depression during adolescence has been linked to aspects of both the family environment and brain developmental processes, although few studies have explored these two key variables together to prospectively determine adolescent vulnerability to depression. Consequently, the aim of the present thesis was to determine whether volume change in the pre-frontal cortex (PFC), amygdala and hippocampus partially, but significantly, mediate the effects of maternal behaviours on the onset of depression during adolescence. A secondary aim of this study was to explore a specific mechanism through which these changes in the brain may occur; specifically, systemic inflammation as marked via the production of CReactive Protein (CRP). Overall, it was expected that family interactions charaterised by higher rates and longer durations of Aggressive and Dysphoric maternal behaviours would predict the onset of clinical depression. Moreover, it was hypothesized that such maternal behaviours would predict changes in brain volume previously reported in depressed samples, as well as increased levels of CRP. Lastly, it was anticipated that elevated levels of CRP associated with more hostile maternal behaviours would partially, but significantly, mediate the relationship between parenting and structural brain development. Data from the larger Adolescent Development Study (ADS) were used to explore these aims and hypotheses. The ADS is a prospective longitudinal research study that consists of four waves of data collection, with data for this research project drawing on each of these four data collection time points in the following areas; magnetic resonance imaging (MRI) (T1, T3 and T4), family interaction tasks (T1), diagnostic assessment of mental health (T1 -T4) and saliva samples to measure inflammation (T2). As such, participants in this research comprised a smaller sub-sample of the total ADS sample population. This sub-sample consisted of N = 160 adolescents (females = 80), of which N = 32 (females = 22) received a diagnosis of clinical MDD. Path analysis techniques were used to analyse the data. The findings from the present study confirmed that maternal behaviours and changes in brain volume over time both increase vulnerability to MDD onset during adolescence. However, no evidence was found that changes in brain volume across the ages of 12 to 19 years in the PFC, amygdala or hippocampus mediated the effects of these maternal behaviours on mental health outcomes. Moreover, maternal behaviours were also found to result in detectable changes in brain volume over time, highlighting how even subtle variations in parenting behaviour influences biological development. However, when the immune system was included in these analyses, results suggested that CRP did not mediate the influence of maternal behaviours on these structural changes in the brain. The complexities of these interactions and their implications for our understanding of etiological models of depression during adolescence are considered.
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ItemDevelopment of the prefrontal cortex and its relationship to self-regulatory abilities during adolescence( 2014)Adolescence is a period of significant brain maturational changes in regions associated with self-regulation. While normative patterns of cortical thinning are postulated to underlie adaptive functioning, aberrations of this process are thought to result in poor self-regulatory abilities. This study characterises the development of three regions known to underlie regulatory processes, the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC) and ventrolateral prefrontal cortex (vlPFC), during adolescence. The study also examines the relationship between development of these cortical regions with three aspects of self-regulation: i. temperamental effortful control, ii. proactive and reactive forms of cognitive control, and iii. cognitive reappraisal, an adaptive emotion regulation strategy. Ninety-two adolescents (47 females) were examined longitudinally during early (mean age = 12.67), mid- (mean age = 16.42) and late adolescence (mean age = 18.78). Structural MRI scans were obtained at early and mid-adolescence, and cortical thickness of the regions of interest was measured using a semi-automated software (FreeSurfer). Effortful control (measured using the Early Adolescent Temperament Questionnaire-Revised), and proactive and reactive cognitive control (measured using a modified Stroop task), were also examined at early and mid-adolescence. Finally, cognitive reappraisal was measured at late adolescence using the Emotional Regulation Questionnaire. Linear mixed models were employed to analyse brain development between early and mid-adolescence, including sex and hemisphere effects. Subsequently, general linear and linear mixed models were employed to investigate the relationship between change in cortical thickness and change in effortful control/cognitive control over time. Finally, general linear models were employed to investigate the relationship between change in cortical thickness and use cognitive reappraisal strategies during late adolescence. Sex effects were included in all models. Findings revealed that the ACC, dlPFC and vlPFC exhibited significant reductions in cortical thickness between early and mid-adolescence across both hemispheres and sexes. Greater effortful control across time (i.e., averaged across early and mid-adolescence) was related to greater thinning of the left ACC, dlPFC and vlPFC over time, while greater proactive cognitive control across time was related to greater thinning of the right ACC. In addition, greater thinning of the left dlPFC and vlPFC was related to greater engagement in cognitive reappraisal during late adolescence in females. In relation to the development of self-regulation, greater relative increase in effortful control was related to greater thinning of the left dlPFC at trend level. However, greater relative increase in proactive control was related to less thinning of the right vlPFC, and greater relative increase in reactive control was related to less thinning of the left ACC (the latter in males alone). These findings highlight a complicated and dynamic relationship between cortical and self-regulatory development during adolescence, with different patterns of cortical maturation being advantageous for different forms of self-regulation. The importance of investigating sexual dimorphism in brain-behaviour relationships is also emphasised, as different associations were identified between cortical maturation and self-regulation in males and females. These findings suggest that early to mid-adolescence is a developmentally sensitive period for self-regulation, and provide a foundation for understanding abnormal patterns of brain development, and associated behavioural difficulties and psychopathology.
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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.
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ItemThe neuroendocrine system following preterm birth and its effects on cognitive and brain development at age 7( 2012)Preterm birth is associated with a well-defined pattern of neurodevelopmental impairments which include a range of cognitive deficits, as well as structural brain abnormalities. Further, preterm infants are known to have a transiently altered neuroendocrine system during the first weeks of postnatal life. Although recent studies have focused on characterising long-term neurobehavioural deficits, few have examined potential mechanisms that may, at least partly, explain these poorer outcomes. This study aimed to address this shortcoming by focusing on the postnatal neuroendocrine system and its association with neurodevelopmental outcomes at age 7 in a group of children born very preterm. Postnatal concentrations of three hormones, free thyroxine, cortisol, and growth hormone, were examined using both direct hypothesis testing and exploratory hypothesis-generating approaches. Three direct hypotheses were proposed following review of the literature. Firstly, it was hypothesised that lower postnatal free thyroxine concentrations would be associated with poorer performances on measures of intellect, attention, and visuoperceptual abilities, as well as reductions in grey and white matter volumes at age 7 in children born very preterm. Secondly, it was hypothesised that higher postnatal cortisol concentrations would be associated with poorer performances on tasks of new learning and memory and volumetric reductions in the hippocampi at age 7 in children born very preterm. The final hypothesis predicted that elevated postnatal growth hormone concentrations would be related to deficits in attention and executive functioning and reductions in the prefrontal brain volumes at age 7 in children born very preterm. The current study investigated 83 children born very preterm (gestational age <30 weeks and/or birth weight <1250g), born between June 2002 and December 2003 in Melbourne, Victoria. During the neonatal period, hormone analysis was conducted over eight time points during the first 42 days of life (cord, Day 1, Day 4, Day 7, Day 14, Day 21, Day 28, and Day 42) to characterise the hormone profiles associated with preterm birth. At age 7, the children participated in a cognitive assessment and an MRI scan. A broad neuropsychological battery that assessed six domains of cognition, namely intellect, language, visuoperceptual reasoning, memory, attention and executive functioning, and processing speed, was used to characterise the cognitive profiles of this group of children. MRI imaging analysis was conducted using Freesurfer (v 5.1.0) to obtain cortical and subcortical brain volumes. The results did not confirm the direct hypotheses, although some interesting and novel findings arose. Firstly, elevated free thyroxine concentrations were related to poorer processing speed performances. A similar relationship was observed with elevated cortisol concentrations and decrements in processing speed. Lastly, elevated cortisol concentrations were related to volumetric reductions in subcortical regions, particularly the basal ganglia. Possible explanations for these findings were reviewed, though more research is required to confirm these relationships. Using a critical illness theory of endocrinology, it was concluded that the hormone profile exhibited by this cohort of children born very preterm during the early postnatal period, namely low concentrations of free thyroxine, and elevated concentrations of cortisol and growth hormone, reflected a transient reaction to acute critical illness. Moreover, given the adaptive nature of this acute illness phase, it was concluded that this postnatal hormone profile did not explain the diffuse nature of the neurodevelopmental impairments common to the preterm population.