Melbourne School of Psychological Sciences - Theses
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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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ItemEmotional self-awareness and depressive symptoms: an investigation of an early intervention mobile phone self-monitoring program for adolescents( 2012)Up to 30% of adolescents experience depressive symptoms before 18 years of age and are at risk of developing severe recurrent depression. There is, however, a lack of appropriate treatments available for these young people. Self-monitoring is often used in therapy to increase awareness about mood and distress, and is likely to decrease depressive symptoms. Furthermore, self-monitoring has potential as an early intervention tool for young people at risk of depression, particularly when mobile phones are used as a medium. Using both qualitative and quantitative methods, this thesis investigates the concept of emotional self-awareness (ESA) and its mediating role in the relationship between self-monitoring and depressive symptoms. To this end, several studies were conducted. First, a systematic literature review examining the benefits of ESA was conducted. A review of 50 publications found five common themes throughout the literature regarding ESA: (a) becoming aware of an emotional experience; (b) the ability to define and distinguish specific feelings; (c) identifying the contextual factors surrounding emotions; (d) communication of emotional knowledge; and (e) analysing emotional events to make decisions. Second, a post-hoc qualitative study examined secondary school students’ general feedback about ESA after self-monitoring. Spontaneous feedback from 20% of participants reported at least one ESA theme after completion of the self-monitoring program. Third, following from the post-hoc study, in-depth qualitative interviews were conducted with 37 young people after self-monitoring, specifically targeting ESA. This study provided rich descriptive detail about the themes of ESA from young people’s perspectives. Fourth, a preliminary measure of ESA was developed and tested with 22 young people with subclinical depressive symptoms, recruited from two general practitioners in a rural setting. This small-scale mixed-methods study combined an in-depth qualitative interview and a quantitative measure of ESA. Young people with high scores on the ESA measure had a different qualitative experience than those with low scores. Last, a randomised controlled trial examined the effects of self-monitoring on depressive symptoms when mediated by ESA. Young people with mild or more depressive symptoms were recruited from primary care settings and randomised into an intervention group (n = 68) or an attention-comparison group (n = 46). Mediation analysis demonstrated that self-monitoring significantly increased ESA in the intervention group when compared with the comparison group and that an increase in ESA significantly decreased depressive symptoms. Furthermore, there was a medium size of indirect effect (κ2 = 0.44) for depressive symptoms per week indirectly through ESA when compared with the comparison group. In summary, a useful model of ESA was developed in this thesis and tested across the studies suggesting that self-monitoring can increase ESA, which in turn, decreases depressive symptoms. Mobile phones are well suited to early intervention programs, providing an alternative to watchful waiting. Mobile phone self-monitoring programs should be considered as a first-step low-cost early intervention for young people who are at-risk of mental health problems. Self-monitoring has the advantages of helping young people increase their ESA while gaining more information about their mental health symptoms, which can also direct them to suitable interventions.
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ItemThe role of positive affect and depressive illness in the structural development of the neural reward system during adolescence( 2012)Disturbances in positive affect are a primary feature of depressive disorders. The relationship between positive affect and depression has long been described in the personality and temperament literature, and, consistent with the definition of temperament, a biological basis for this relationship has been proposed. Over the past two decades a growing body of evidence suggests an association between neurological systems hypothesised to support the experience of positive affect, particularly the dopaminergic reward system, and depression. Interestingly, neurodevelopmental research has shown that the development of the dopaminergic system undergoes significant remodelling during adolescence, a period of life that, relative to childhood, is associated with a marked increase in risk for developing a depressive illness. These coincident effects have led researchers to postulate that brain development during this period of life may be related to both normal and abnormal changes in positive affectivity observed in adolescence; however there have been very few clear expositions of the particular mechanisms involved in determining healthy or pathological outcomes. To date there have been very few empirical investigations of the relationships between positive affect, brain development and depression. This study aimed to address this shortcoming by prospectively describing structural brain development in key subcortical regions of the dopaminergic reward system (i.e., nucleus accumbens, hippocampus, pallidum, caudate, putamen) in a group of adolescents at high and low risk (determined by childhood temperament) of developing depression. Volumetric change was the chosen variable of interest firstly because it can be meaningful described longitudinally, and secondly, because there is a gap in current knowledge about how the aforementioned structures change volumetrically during this period of life. After a review of the literature, a model was proposed that described how dysregulated positive affect might contribute to abnormal brain development in the dopaminergic reward system during adolescence. Subsequently, three key aims for this investigation were described. The first aim was to further clarify normal structural development, and it was hypothesised that all regions of interest would undergo significant volumetric change consistent with previous descriptions (Study 1). Secondly, it was hypothesised that temperamental positive affect measured prior to adolescence would predict differences in brain development in reward related regions (Study 2). Finally, it was hypothesised that the experience of depression during early to middle adolescence would be associated with deviant brain development relative to healthy controls during this period of life (Study 3), and that this pattern of development would be similar to that described for individuals with low positive affect (i.e., patterns described in Study 2). The current study longitudinally investigated a community sample from metropolitan Melbourne, Australia, of 89 adolescents at ages 12 and 16 years that were selected based on high/low risk for depressive illness. Children with a prior history of depressive illness were excluded, allowing for a prospective investigation into the onset of depression during adolescence. Structural MRI data, cognitive ability, depressive symptoms and lifetime clinical diagnoses were obtained at both assessments. Temperamental measures of positive affect were obtained at the baseline assessment. MRI imaging analysis was conducted using Freesurfer (v 4.5; longitudinal stream) to obtain subcortical brain volumes from both time points. In Study 1, the overarching hypothesis that each of the ROIs would undergo significant change was generally supported, and some novel findings regarding sex differences and hemisphere effects were observed. In Study 2, lower levels of positive affect were associated with smaller left hippocampal volumes. Developmentally, positive affect moderated development of the right hippocampus and right caudate, whereby lower levels of positive affect were associated with smaller changes in volume over time (i.e., less plasticity) relative to higher levels of positive affect. In Study 3, the experience of depressive illness in early adolescence was associated with deviant brain development, relative to healthy adolescents, in the left (both sexes) and right (females only) caudate and the left (both sexes) and right (females only) putamen. Furthermore, independent of time, depressed males had smaller left hippocampal volumes. There was some support for the hypothesis that the deviant development associated with depression was similar to that associated with temperamentally low positive affect, although the effects associated with depression were more widely distributed across the subcortical regions and moderated by sex. These findings were contextualised within the current literature and possible explanations for these findings were reviewed. It was concluded that brain development during adolescence is influenced by the experience of positive affect, and it was suggested that this might be a biological mechanism that further explains the prospective relationship between temperament and depressive illness during adolescence. Furthermore, the alterations to brain development trajectories associated with the experience of depression may act like a biological scar, which could contribute to the high risk of recurrence associated with adolescent onset depression. The finding of developmental effects, as well as the difficulty of integrating some of the findings with the existing adult and child literature from cross-sectional investigations, strongly emphasised the importance of taking a developmental perspective when studying the relationships between brain structure and depression. Finally, conceptual challenges regarding an evolving definition of positive affect (i.e., one that draws upon psychological and neurobiological perspectives), as well as clinical implications arising from this study, particularly relating to early intervention strategies targeting low positive affectivity, were discussed. Throughout the final chapter several suggestions for future research are discussed.
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ItemDepression and immunity in adolescents: early precursors to disease?( 2012)Inflammation and immune dysfunction have been proposed to be mechanisms relevant to clinical depression. However, research on this topic is limited by the paucity of lifespan and longitudinal studies, making it difficult to address causality. This project aimed to examine inflammatory and depressive measures in adolescents from the community using both cross-sectional and prospective longitudinal designs. Experiment 1 was a cross-sectional, two-group study of 13 clinically depressed adolescents aged 13-18 years (11 females), and 13 age- and sex-matched healthy controls, both recruited from the community. Sixteen cytokines were measured in saliva and serum. Depressed adolescents displayed significantly elevated levels of C-reactive protein (CRP), Haptoglobin, Serum Amyloid P (SAP), and Alpha-2-macroglobulin (A2M) in saliva compared to controls, but not in serum, or for any other cytokine. Depressed adolescents also did not display a higher ratio of T helper cell 1- to T helper cell 2-type cytokines compared to controls. Experiment 2 was a prospective study of 67 adolescents (27 females) followed from 12-18 years of age and recruited from the community. Self-report depressive symptoms measured by the Center for Epidemiological Studies Depression Scale (CES-D) and Axis-I psychopathology measured by The Schedule for Affective Disorder and Schizophrenia for School-age Children (KSADS) were measured at four phases, and four salivary acute-phase proteins (CRP, Haptoglobin, SAP, and A2M) were measured at Phase II. Temperamental negative emotionality (NEM) was also assessed at age 12. Results showed that elevated CRP was significantly correlated with elevated CES-D scores cross-sectionally, but no inflammatory markers predicted the onset of a depressive illness or an increase in depressive symptoms over time. There was a significant Sex x CRP interaction effect on CES-D measured at Phase I, II, and IV, with a relationship between CRP and CES-D only apparent for females. Examining only females demonstrated significant associations between CRP and CES-D at all four phases, including CES-D measured two years prior to inflammation, suggesting that for females, depressive symptoms may precede elevated levels of CRP, however, further longitudinal research is required that measures inflammation at more than one time point. At Phase II, there were significant interactions of NEM temperament x CRP on CES-D, with a relationship between CRP and CES-D only for those with a high NEM score. Post-hoc analyses showed that body mass index (BMI) was also a significant moderator of the relationship between CRP and CES-D at Phase II, with a stronger association for participants with a higher BMI score. Measures of early-life stress and childhood trauma were not associated with inflammatory markers. These results suggest that salivary CRP is a marker of adolescent depression, but levels of this inflammatory marker do not predict the development of depressive illness. The results, along with other research, suggest that depressive symptoms may be a risk factor for chronic inflammation and associated medical diseases, especially for females. Furthermore, obesity may be another consequence of depression which can lead to this observed elevated inflammation. Finally, sex hormones should be considered in models of depression, obesity, and inflammation.
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ItemMood and anxiety outcomes in adolescents born with extremely low birthweight or extremely preterm: prevalence and neuroanatomy( 2012)Preterm birth is associated with poor outcome in a range of domains, which can persist into adolescence and beyond. This may include poor mental health outcomes, and particularly, anxiety and depressive symptoms. To date, studies of mood and anxiety outcomes in preterm groups have mainly used dimensional measures of symptoms; only a handful employ clinical diagnostic instruments and these largely focus on recent symptoms. Our understanding of the prevalence of clinically diagnosable disorders is consequently limited, particularly in late adolescence and for those born since 1990. Prematurity at birth can also have a significant and longstanding impact on brain development. An extended medial network, including the hippocampus, amygdala, and medial prefrontal cortex, is implicated in emotion regulation, as well as clinical mood and anxiety disorders. Hippocampus, amygdala, and prefrontal structure may be altered in preterm samples, but potential relationships between these brain regions and emotional outcomes are yet to be explored in preterm survivors. This study aimed to address these limitations in the current literature by i) characterising mood and anxiety outcomes in adolescents born extremely low birthweight or extremely preterm (ELBW/EP), ii) characterising the structure of regions in the extended medial network, and iii) investigating the relationships between these outcomes and brain structure. A number of specific hypotheses arose from this research question. Firstly, it was expected that the ELBW/EP group would report more recent symptoms, more frequently meet diagnostic criteria for current or past disorder, and more strongly endorse personality traits associated with anxiety and depression than a normal birthweight (>2500g; NBW), full-term (>36 weeks; FT) control group. Secondly, it was expected that ELBW/EP participants may have smaller hippocampus, amygdala, and ventromedial prefrontal cortex volumes, and thinner ventromedial prefrontal cortices, than NBW participants. Finally, it was predicted that structural reductions in these regions of interest would be associated with greater mood and anxiety symptoms, and a history of clinically diagnosable disorder, in ELBW/EP and NBW participants. This study assessed 215 ELBW/EP and 157 NBW adolescents who were born in 1991 and 1992 in the state of Victoria, Australia. Participants from a prospective geographical cohort were followed up at age 18 and completed measures of mood and anxiety symptoms and disorders (including questionnaires and a structured clinical interview), as well as personality traits. Participants also underwent structural MRI scanning, and cortical and subcortical brain volumes were generated using FreeSurfer (v5.0). Unexpectedly, there was no elevation in clinically relevant recent or lifetime history of depression or anxiety in the ELBW/EP group. Although mood and anxiety disorders were more prevalent in females overall, there was no interaction between group and gender. The ELBW/EP group had disproportionately smaller bilateral hippocampus volumes and left amygdala volumes than controls, and the ventromedial prefrontal cortex was proportionately larger and thicker in the ELBW/EP group than the NBW group. Recent mood and anxiety symptoms were not well predicted by any of the neuroanatomical variables of interest. Despite this, lifetime history of a mood or anxiety disorder was associated with smaller left vmPFC volumes. Further analyses indicated this pattern was apparent in those with a history of anxiety disorder but not mood disorder. Group did not moderate these findings. Assessment of ELBW/EP adolescents’ self-reported mood and anxiety outcomes revealed an encouraging picture. Although extremely low birthweight or extreme prematurity was associated with altered structure of regions in the extended medial network, these alterations appeared to have limited relationship with outcomes. These findings contribute to the literature by examining older adolescent mood and anxiety outcomes and using high field-strength neuroimaging. The implications for preterm survivors and the relevance of brain structure to mood and anxiety outcomes in this age group are considered.