Melbourne School of Psychological Sciences - Theses
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ItemTuning in to teens: examining the efficacy of an emotion-focused parenting intervention in reducing pre-adolescents’ internalising difficulties( 2014)The transition from childhood to adolescence coincides with an increase in anxiety, a peak in somatic complaints, and a post-pubertal rise in depression by mid-adolescence, particularly for girls. For those affected, internalising difficulties result in considerable stress and impairment for the young person even if symptoms do not reach criteria for clinical diagnosis. Up to 50% of all adult psychological disorders have their onset during adolescence, highlighting the importance of identifying methods of prevention that are evidence-based. Emotional competence has been found to be an important protective factor for healthy social, emotional, and behavioural functioning. Both adolescents and adults with internalising difficulties show deficits in aspects of emotional competence. Research in child development suggests that parents’ emotional competence and emotion socialisation practices are related to children’s emotional functioning, including child internalising difficulties. This research has not yet been translated into intervention or prevention programs targeting parents of adolescents. The current study examined the efficacy of the Tuning in to Teens parenting program in improving emotion socialisation practices in parents of pre-adolescents and in measuring the impact on youth internalising difficulties. Grounded in emotion socialisation theory, this program teaches parents skills in responding to emotions in ways that enhance emotional competence in the young person, while also improving parent-youth communication and connectedness. A group-randomised control design was used where participants were recruited from schools and randomised into intervention and control conditions. Data were collected from 225 parents and 224 youth during the young person’s final year of elementary school (6th grade) and again, 10 months later in their first year of secondary school (7th grade). The thesis includes three studies. Study 1 reports the results of multilevel analyses, which showed participation in Tuning in to Teens resulted in significant improvements in parental emotion socialisation and reductions in youth internalising difficulties for the intervention condition. Study 2 examined moderators and mediators of program outcome. Results showed greater program effects for intervention subgroups with high pre-intervention difficulties. Parental education, income, parental internalising difficulties, parental difficulties in emotion awareness and regulation, and attendance rate did not moderate program effects. Mediation analyses supported emotion socialisation theory and showed parents who participated in the Tuning in to Teens parenting program reported improvements in emotion socialisation, which in turn was related to reductions in youth internalising difficulties. Study 3 investigated the relationship between parent emotion socialisation and youth somatic complaints. The study extended the literature on somatic complaints by being the first to consider parents’ emotional competence and emotion socialisation practices as predictors of youth somatic complaints alongside parents’ own somatic complaints. Results indicated that changes in parents’ awareness and regulation of emotion and emotion socialisation practices resulted in reduced youth somatic complaints. These findings have important implications for current aetiological models of somatic complaints and provide support for using an emotion-focused approach to enhance current treatment models of youth somatic complaints. A significant contribution of this thesis is that it presents the first randomised control trial evaluation of a parenting program that utilises research linking parents’ emotion socialisation with young people’s mental health, applying it in practice with a sample of parents of pre-adolescents. The research findings provide support for emotion socialisation theory and for using an emotion focused parenting program to prevent internalising difficulties in early adolescence.
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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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ItemNeighbourhood disadvantage and internalising symptoms in adolescents: the mediating role of stressful life events, temperament, and maternal aggression( 2013)Purpose of the study: Disadvantaged neighbourhoods are associated with increased risk for anxiety and depression in adolescents. However the mechanisms for this relationship are not fully understood. Using a longitudinal design, I investigated whether several potential mediators, including stressful life events, maternal aggressive, dysphoric and positive behaviour, and adolescent temperament (Surgency, Negative affectivity, Effortful Control, Affiliation), could help explain the relationship between neighbourhood disadvantage and symptoms of anxiety and depression in early- to mid-adolescence. Method: A community sample of 245 adolescents and their parents participated in a range of assessments at baseline (age approximately 12-13 years old), including an observational assessment of parent-adolescent interactions, and a battery of adolescent-rated questionnaires. Neighbourhood disadvantage was assessed by combining Postal Area data collected during this first wave of assessment with a measure of disadvantage called the Socio-Economic Indexes For Areas (SEIFA) developed by the Australian Bureau of Statistics Adolescents were followed-up approximately 4 years later and completed questionnaires assessing depressive and anxious symptoms. Results: Analyses revealed that adolescents from disadvantaged neighbourhoods were more likely to report a greater number of stressful life events, and depressive and anxious symptoms. They were also more likely to score higher on temperament measures of Negative Affectivity, and lower on measures of Surgency and Effortful control. Mothers from disadvantaged neighbourhoods were more likely to display aggressive and dysphoric behaviour for longer periods, and positive behaviour for shorter periods, however no differences were detected in regard to the frequency of these behaviours. Mediational analyses using a bootsrapping approach determined that stressful life events and three temperament dimensions (low Surgency, low Effortful Control, high Negative Affectivity) significantly mediated the relationship between neighbourhood disadvantage and symptoms of anxiety and depression at baseline. Stressful life events and maternal aggression significantly mediated the relationship between neighbourhood disadvantage and change in depressive and anxious symptoms from baseline to follow-up. Conclusion: The research reported in this thesis provides evidence that disadvantaged neighbourhoods differ from less disadvantaged neighbourhoods in several different ways. In addition, various factors were found to partially mediate the relationship between neighbourhood disadvantage and anxiety and depression at different periods during adolescence. Temperament appears to be important earlier in adolescence, maternal affective behaviour seems to be important during mid- to later-adolescence, while stressful life events appear to act throughout adolescence. These findings suggest that the neighbourhood environment is likely to influence adolescents both directly, and indirectly through its effects on more proximal and individual risk factors. It was concluded that prevention and intervention programs targeting a range of risk factors in adolescents from disadvantaged neigbourhoods could be particularly effective at reducing the prevalence of internalising disorders in adolescents.
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ItemGetting to the heart of teen depression: the relationship between depression and cardiovascular risk in adolescents during wakefulness and sleep( 2013)Depression has been identified as an independent cardiovascular risk factor in adults, where its presence results in higher rates of mortality and adverse cardiac events in patients with and without known cardiovascular disease (CVD). Recent literature suggests preclinical signs of cardiovascular risk are also present in adolescents experiencing depressive symptoms, however little is known about the effects of adolescent clinical depression on cardiovascular health. Moreover, no study has investigated the cardiovascular functioning of clinically depressed individuals during sleep, a state which involves cardiovascular changes including the characteristic decrease or ‘dip’ in blood pressure (BP). The aim of this study was to determine whether clinical depression is associated with an increased risk of cardiovascular disease in otherwise healthy adolescents. Experiment One sought to examine cardiovascular functioning during quiet wakefulness. Participants (n = 889, 352 male) aged 12-18 years were recruited from Victorian secondary schools in the general community. Subsequent to completing mood questionnaires and clinical interviews, 50 eligible participants (25 [6 male] clinically depressed, 25 [6 male] control) took part in a morning cardiovascular assessment at the University of Melbourne. Variables assessed included automatic clinical and continuous beat-to-beat finger arterial BP, heart rate (HR), endothelial functioning, pulse transit time (PTT), as well as cholesterol, glucose and glycohaemoglobin levels. In addition, the cumulative risk of present modifiable risk factors such as smoking was calculated according to the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) risk score, which has been shown to predict coronary calcification in young populations. It was predicted that, compared to controls, depressed adolescents would show evidence of a number of early pathophysiological processes. As hypothesised, between-group analyses revealed depressed adolescents had significantly poorer endothelial functioning, which resulted in decreased vasodilation, and shorter PTT suggesting deterioration in vascular integrity and structure. Depressed adolescents also presented with higher fasting glucose and higher triglyceride levels compared with controls. Furthermore, risk score calculations revealed significantly higher PDAY risk scores in the depressed group indicative of increased engagement in unhealthy behaviours and a higher probability of having advanced atherosclerotic lesions. Contrary to predictions however, no significant differences were found in BP or HR measurements. In order to have a more complete understanding of the cardiovascular health of depressed adolescents, Experiment Two was designed to asses BP and HR during sleep. The BP profile at sleep onset was of particular interest as a blunted decline in BP is associated with target organ damage and increased cardiovascular risk. A subgroup of female participants (8 clinically depressed, 10 control) who completed Experiment One also participated in an overnight cardiovascular assessment. Whole-night polysomnography was conducted with continuous beat-to-beat finger arterial BP and HR monitored via Portapres and ECG, respectively. Data were analysed as an average of the first 6 hours of sleep as well as 2-minute epochs of stable sleep averaged within sleep stages. Further analyses of 30-second epochs were averaged across the pre-sleep wakefulness and the first ≥5 minutes of continuous stable Stage 2 in the sleep onset period. Analyses revealed that although no significant group differences in BP or HR were found during morning wakefulness, depressed adolescents presented with higher systolic, diastolic and mean arterial BP across the whole night and across sleep stages. The difference between groups (~11 mmHg) was found to not only be statistically but also clinically significant. Depressed adolescents also displayed a blunted systolic BP decline at sleep onset compared with controls. This heightened nocturnal BP and blunted decline represent early changes in BP regulation and could be a preclinical marker for depressed adolescents at high risk of cardiovascular disease. A number of plausible mechanisms may explain the heightened BP including a failure to shift to parasympathetic dominance during sleep, increased cortisol levels as a result of a dysregulated hypothalamic-pituitary-adrenocortical axis, and limited vasodilation at night due to endothelial dysfunction as found in Experiment One. Although the mechanisms are still unclear, the results suggest that depression has a significant adverse effect on the cardiovascular system in the early stages of life. Given that risk factors are known to continue to adulthood, the heightened nocturnal BP, increased triglyceride and vascular changes may increase risk for future cardiovascular problems such as hypertension. Identification of those at high-risk and intervention should therefore be actioned as early as adolescence as a way to decrease the prevalence and global burden of CVD.
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ItemBrain network correlates of adolescent self-control( 2013)The ability to engage self-control by overcoming automatic habits and impulses is critical to the progression from adolescence to adulthood, and can predict long-term health outcomes. Research into self-control has involved a number of techniques, with the psychology of individual differences and cognitive neuroscience featuring prominently. Despite their diverse perspectives, these two fields have converged recently to suggest that variations in both cognitive and personality-based measures of self-control rely on a common set of functional interactions within and between two canonical large-scale brain systems: The so-called cognitive control (CCN) and default-mode networks (DMN). However, very little is known about how individual differences in self-control during the teenage years relate to the functional activity and connectivity of these networks. This thesis aimed to fill this gap using a series of functional magnetic resonance imaging (fMRI) experiments designed to assess, in detail, the large-scale functional brain networks that support adolescent self-control as defined using both cognitive and questionnaire-based measures. To achieve this, data from the same sample of participants was used in a series of five experiments that progressed in the focus on large-scale brain networks from simple brain mapping, through individual differences analyses of activity and functional connectivity, and then ending with modularity analyses. During each experiment, a specific interest was also to determine the similarities and differences between the task-related versus the resting-state CCN and DMN to determine how self-control networks are engaged during task performance. The main hypothesis was that the task-related activity and functional connectivity of core regions that comprise the CCN and DMN would be most related to individual differences in cognitive and effortful control. Methods: The participants comprised a healthy sample of adolescents (N=73; mean age (SD) =16.5(0.5); 51% female) from a longitudinal study who completed questionnaire measures of effortful control, a temperamental index of self-control capacity in daily life; an fMRI interference control paradigm (the Multi-Source Interference Task; MSIT); and a resting-state fMRI sequence. Using these data, five experiments were then devised to investigate how the task-related activity, task-related functional connectivity, and resting-state functional connectivity of the CCN and DMN support self-control behaviours as measured by self-reported effortful control (ECc), parent-reported effortful control (ECp), MSIT interference effect, and MSIT accuracy. The experiments were designed to build upon each other to comprehensively address the thesis aim. Chapter 6 established the main measures used throughout the thesis related to the sample, and to the behavioural and brain measures related to self-control. The second experimental chapter (Chapter 7) examined how MSIT-related activation and within each region comprising the CCN and DMN correlated with EC and MSIT performance. Chapter 8 then established the functional connectivity parameters for each participant and employed the graph theoretic measure of node strength to investigate correlations between behaviour and the resting-state and task-related functional connectivity of each region. More specific pair-wise functional connectivity relationships between brain regions were then investigated in Chapter 9 in order to identify functional connectivity sub-networks related to each behavioural variable. Finally, Chapter 10 then integrated the results into a broader functional connectivity picture using a data-driven technique to identify how the putative network nodes aggregated into functionally specialized modules. Results: Contrary to the main hypothesis of this thesis, the results indicated that each behavioural measure was related to a different large-scale brain network, which appeared to be specific to the condition under investigation (i.e., task or rest). For example, the MSIT interference effect was associated with a putative visual attention network during task performance but not at rest; MSIT accuracy was mainly associated with the connectivity of default-mode regions; and effortful control was correlated with complex subnetworks where interactions between the CCN and DMN appeared to be most important. The importance of interactions between networks was then emphasised in the modularity analysis, which showed subtle, but behaviourally important, differences in network modular organization between the task and resting-state conditions. Conclusion: Overall, the results of the thesis supported the idea that competitive and cooperative relationships between the cognitive control and default mode networks support adolescent self-control. However, the experiments highlighted the importance of the engagement of different subnetworks for different measurements of self-control, and functional connectivity differences between rest and task conditions that may predict behaviour. Together, these findings emphasise the importance of considering the flexibility of large-scale networks when considering the neural basis of adolescent self-control, rather than a single canonical brain region or circuit.
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ItemSpeaking for themselves: how do adolescents define their quality of life after a traumatic brain injury?( 2013)Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young people (Yeates et al., 2002). The status of quality of life (QoL) in paediatric TBI is mixed. Our recent meta-analysis of paediatric QoL (Di Battista et al., 2012) found that good QoL outcomes are contingent on milder injuries, proxy reporting and early assessment whereas poor outcomes reflect more severe injuries and later assessment. Available paediatric QoL data is largely based on the health-related quality of life (HRQoL) paradigm; where a good outcome is contingent on what one can accomplish or achieve, as assessed by proxies. Information on the subjective well-being (SWB) component of QoL is limited. When estimating the HRQOL in adolescents, the presence of anxiety and depression and the quality of social relationships are important considerations, because adolescents are entrenched in social development during this phase of maturation. The influence of anxiety, depression and loneliness on HRQOL in adolescent survivors of TBI has not been documented. The goal of this study was to explore the adolescent experience of quality of life, anxiety, depression and loneliness after a traumatic brain injury. This study is a mixed-methods assessment of the impact of mood states and loneliness on quality of life (QoL) in adolescents who have survived a traumatic brain injury (TBI). METHOD: mixed method/cohort pilot study (11 adolescents, mild to severe TBI; 9 parents), using self-report (anxiety, depression, HRQoL, loneliness) and proxy-report measures (anxiety, depression and HRQoL) and clinical psychiatric interviews (adolescent only). The adolescent experience of these states is not accurately reflected by parental proxy. Self-reported depression and age at injury were associated with health-related quality of life outcomes, while anxiety was not. Severity of injury was not related to secondary outcomes. Adolescent narratives revealed that having experienced a TBI does not a priori impact upon perceived QoL. The impact of a TBI on QoL could be positive or negative. Post-injury changes in ability were not always attributed to the injury, but rather to a sense of normal age-related changes as identified by the adolescent. Changes as a result of the injury were not always considered important to the adolescent’s view on QoL. Adolescents identified social and inter-personal discrepancies and the emotional consequences of these discrepancies. Ultimately, the individual’s appraisal of their identity from pre to post injury life related to their current sense of well-being. Friendships were very important considerations for post-injury well-being. Processes of post-traumatic growth were identified in the adolescent narrative. The findings of this study are novel and have important implications for both research study design and clinical care settings involving adolescent survivors of a TBI.
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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.