Melbourne School of Psychological Sciences - Theses

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    Predicting and improving the use of CPAP therapy in individuals with obstructive sleep apnoea
    Tolson, Julie Ann ( 2023-02)
    Obstructive sleep apnoea (OSA) is a common chronic sleep disorder characterised by the repetitive narrowing or collapse of the upper airway during sleep. Consequences of untreated OSA include fragmented sleep, intermittent hypoxia, memory deficits, increased risk of cardiovascular events and workplace accidents, and changes in mood, particularly depression. Comorbid depression is highly prevalent in OSA samples, and it is difficult to diagnose one condition in the presence of the other due to symptom overlap. Continuous positive airway pressure (CPAP) is the treatment of choice for moderate to severe OSA. However, CPAP use is suboptimal in many individuals. As such, there remains a significant burden of OSA on the individual and the healthcare system. The work presented in this thesis was part of a larger randomised controlled trial, the CPAP for OSA and Depression (COSAD) trial. The three experimental studies reported herein (Chapters 3-5) stemmed from the COSAD study design. Patients recently diagnosed with OSA and referred to the Austin Health sleep laboratory for CPAP implementation were recruited for this trial. Study 1 examined predictors of CPAP use up to 4 months post CPAP initiation. Predictors included patient and disease characteristics, sex, age, BMI, OSA severity, psychological variables (anxiety and depression), behaviour change variables (decisional balance and processes of change, and self-efficacy, which is comprised of 3 constructs; risk perception, outcome expectancies and CPAP self-efficacy), the first week of CPAP use, and wait time to CPAP initiation. A delay of 95 days to CPAP initiation was not associated with any differences in CPAP use at 1 week, 1 month and 4 months. Female sex, processes of change and self-efficacy were associated with CPAP use at 1 week. Average nightly CPAP use at 1 week was associated with CPAP use at 1 month and 4 months. No other patient or disease characteristics or psychological variables were associated with CPAP use up to 4 months. Study 2 investigated the effect of treating OSA with CPAP therapy on mood and sleepiness. Mood, including depression, anxiety and stress, were measured at baseline and 4 months and were compared between an intervention group (participants underwent 4 months of CPAP therapy for OSA) and a waitlist control group (participants were not treated for OSA). Stress improved in females with 4 months of CPAP therapy compared to females in the control group. Sleepiness, but not mood, improved after 4 months of CPAP therapy compared to control. Study 3 investigated the effect of a multi-dimensional intervention on CPAP use and self-efficacy compared to treatment as usual. CPAP use and self-efficacy improved in the intervention group compared to treatment as usual across the 4-month trial. These findings support previous work that early CPAP use predicts subsequent CPAP use, that CPAP use improves daytime sleepiness and that an intervention can increase CPAP use. Furthermore, this work has advanced the field by demonstrating that a delay to CPAP initiation may not effect subsequent CPAP use. Additionally, there may be sex differences in stress symptoms when treating OSA with CPAP therapy. Implications for future studies include the importance of the early period of CPAP use and the effect of wait time to therapy initiation on subsequent CPAP use.
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    Empathy during childhood; an investigation of associations with anxiety and depressive symptoms, and brain structure and function
    Bray, Katherine Olivia ( 2021)
    This thesis investigated the associations between empathy and internalising (i.e., depressive and anxiety) symptoms, and the underlying structural, and functional connectivity neural correlates of empathy in late childhood. Background: Empathy refers to the understanding and sharing of others’ emotions, is a multidimensional construct, and includes cognitive and affective components. Empathy is important for social functioning, and alterations in empathy have been demonstrated in many developmental/psychiatric disorders. Studies in adults have demonstrated that both cognitive and affective empathy are associated with internalising symptoms. Studies in adults have also examined the neural underpinnings of empathy, implicating two major functional brain networks: the Default Mode Network (DMN) has been implicated in cognitive empathy, while the Salience Network (SN) has been implicated in affective empathy. These findings have mostly resulted from investigating brain activity during empathy tasks (i.e., in functional Magnetic Resonance Imaging [fMRI] studies). Less research has examined the associations between trait empathy, and brain structure or intrinsic functional connectivity. Few studies have investigated these associations between empathy and either internalising symptoms or the neural correlates in young people, particularly children. Investigating associations between empathy, mental health, and brain structure and function during childhood is beneficial to begin to build a comprehensive picture of the development of empathy components and the neural correlates of empathy across the lifespan. Based on previous research in adults and preliminary work in children, we hypothesised that higher levels of empathic distress and lower levels of cognitive empathy would be associated with higher depressive and anxiety symptoms (particularly social anxiety symptoms). We also hypothesised that children’s cognitive and affective empathy would be associated with individual differences in brain structure and function within areas related to the DMN and the SN, respectively. Methods: Participants were 9- and 10-year-old children, a subset from the second wave of the Families and Childhood Transitions Study (FACTS), a longitudinal, community-based cohort study. Sample size across the empirical chapters of the thesis differed depending on measures completed and quality of brain images (study 1 n =127, study 2 n = 125, study 3 n = 112). Self-report measures of empathy (cognitive empathy, affective empathy: affective sharing, empathic concern, empathic distress) and internalising (anxiety and depressive) symptoms were administered, as well as a task-based measure of cognitive empathy. To investigate associations between empathy and internalising symptoms (study 1), canonical correlation analysis (CCA), a multivariate technique, was employed. Participants underwent MRI of the brain where T1-weighted structural images and resting-state functional sequences were collected. Grey matter volume, cortical thickness (study 2), seed-to-whole-brain and dual regression resting-state functional connectivity (study 3) were examined. Results: Study 1: CCA demonstrated that components of affective empathy, specifically affective sharing and empathic distress, were associated with internalising (particularly social anxiety) symptoms. Cognitive empathy was not associated with internalising symptoms. Study 2: In region of interest analyses, individual differences in affective and cognitive empathy were related to grey matter volume in the insula and the precuneus. Although these associations were of similar strength to those found in previous research, they did not survive correction for multiple comparisons. While no associations were detected between grey matter volume and empathy in exploratory whole-brain analysis, associations were found between empathic concern and cortical thickness in the right precentral gyrus. Study 3: Seed-to-whole-brain resting-state functional connectivity analyses demonstrated that both affective sharing and empathic distress were associated with decreased connectivity between key hubs of the DMN (precuneus and temporal parietal junction) and other widespread areas in the brain. Analyses of resting-state networks demonstrated that cognitive empathy was associated with both increased and decreased connectivity between dorsal and lateral regions of the DMN and regions outside of the DMN, including the pre- and postcentral gyrus, and the cerebellum. Affective empathy was associated with increased connectivity between the anterior SN and the pre- and postcentral gyrus. These relationships did not survive strict correction for multiple comparisons. Conclusions: Findings suggested that children who share others’ emotions strongly are more likely to experience anxiety, particularly of a social nature. This study also provided preliminary evidence that individual differences in self-reported empathy in children may be related to certain aspects of brain structure and functional connectivity. Overall, we observed less clear dissociations between the neural correlates of affective versus cognitive empathy, and more widely spread involvement from other brain areas. This potentially indicates reduced maturation and specialisation of the systems underlying affective versus cognitive empathy in this age group. However, more research is required to demonstrate reproducibility of the findings. More research investigating the mental health associations and neurobiological correlates of empathy in children is needed, particularly of a longitudinal nature, to track these changes across development. One limitation of our study is that the majority of our findings were based around self-report measures of empathy, which may not accurately reflect empathic ability.
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    Bugs and Brains: The Gut and Mental Health Study Characterising the gut microbiota in anxiety, depression, irritable bowel syndrome, and their comorbidity
    Simpson, Carra Aven ( 2021)
    Background: The community of microorganisms inhabiting the gastrointestinal tract, collectively known as the gut microbiota, is intimately involved in the maintenance of host health. Comprehensive characterisation of the gut microbiota may enable us to better understand conditions whose pathophysiologies remain poorly understood, including internalising mental health disorders (anxiety and depressive disorders) and irritable bowel syndrome (IBS). While existing research has sought to characterise the gut microbiota in these conditions, the two systematic reviews included within this thesis reveal that studies have failed to consider essential confounders, including age, dietary intake, medication use, biological sex, and body mass index. The inadequate consideration of IBS and internalising disorder co-occurrence was also highlighted. Accordingly, this thesis aimed to investigate the gut microbiota in medication-free females with either IBS or an internalising disorder, as well as females with comorbid IBS and anxiety/depression, whilst controlling for key covariates (age, dietary intake, body mass index). Study 1 aimed to compare the gut microbiota of females with IBS relative to controls, as well as compare microbial composition between the three major IBS subtypes (IBS-diarrhoea, IBS-constipation, IBS-mixed). Study 2 aimed to characterise the gut microbiota of females with an internalising mental health disorder relative to controls. Study 3 aimed to compare and contrast the gut microbiota of females with comorbid IBS and an internalising disorder to controls, as well as to participants with IBS or an internalising disorder separately. Method: This thesis includes 162 females, recruited as part of the Bugs and Brains Study, who belonged to one of four groups: i) 42 controls; ii) 36 participants with an internalising disorder (depressive/anxiety disorder), but no IBS; iii) 42 participants with IBS, but no internalising disorder and iv) 42 participants with both an internalising disorder and IBS. Participants completed comprehensive questionnaires, attended a clinical mental health interview, collected a stool sample, and had their anthropometrics measured within a 1-month period. The gut microbiota was estimated using 16S rRNA gene sequencing on an Illumina MiSeq platform (V4 hypervariable region). Sequences were pre-processed using QIIME2 and following the DADA2 denoising pipeline to produce amplicon sequence variants (ASVs). ASVs were taxonomically assigned against the SILVA database (v.138). Data analysis was performed using R (v.1.3.1073), with the packages phyloseq and picante (alpha diversity), vegan (beta diversity), ANCOM-BC and MaAsLin2 (differential abundance), and randomForest (random forests). Results: Comprehensive multivariate analyses revealed key similarities with regards to the gut microbiota in IBS and anxiety/depression relative to controls. Females with IBS or an internalising disorder tended to be enriched in bacterial species associated with inflammation (e.g., Proteobacteria, Parabacteroides, Alistipes), and participants with either condition harboured a lower relative abundance of immunoregulatory SCFA-producing bacteria relative to controls (e.g., Barnesiella, Bacteroides eggerthii, Lachnospira, Faecalibacterium). Moreover, both the anxiety/depression and IBS groups had higher relative abundances of species known to degrade the essential amino acid tryptophan (i.e., Alistipes). While similar findings were observed in participants with comorbid anxiety/depression and IBS, the gut microbiota composition in this group was heterogeneous, and alterations were not more pronounced than those observed in participants with either disorder separately. Of note, higher abundances of mucin-degrading bacterial taxa were observed in IBS-C and IBS-M relative to controls and the IBS-D group (e.g., Akkermansia muciniphila), suggesting this alteration may be a unique to constipation. Conclusion: This thesis presents a comprehensive characterisation of the gut microbiota in females with IBS, an internalising mental health disorder, and their comorbidity. Similar alterations in the gut microbiota composition relative to controls were identified in these conditions and were not driven by their comorbidity, as participants in the IBS group had no lifetime history of a mental health disorder, and participants in the anxiety/depression group had no lifetime history of IBS. The included studies have great strength in highlighting these findings independent of key confounding factors, including age, dietary intake, BMI, and host sex. Participants in this study were also medication-free and without relevant medical comorbidities. While these studies are well placed to examine the cross-sectional associations between gut bacteria with IBS and internalising disorders, future research should seek to integrate functional analyses and examine other microbial members of the gut microbiota. Longitudinal research designs that combine taxonomic and functional investigations will elucidate the true complexity of gut microbe interactions with host mental health and gastrointestinal functioning.
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    Psychological outcomes of those experiencing early pregnancy loss
    Bendavid, Jessie ( 2019)
    Early Pregnancy Loss (EPL), a loss occurring before 14 weeks gestation, is a relatively common event, occurring in about 20% of pregnancies. Although many women and their partners do not experience psychological difficulties associated with this loss, a significant minority experience intense and sustained grief, depression and anxiety symptoms. Reliable prevalence rates of serious psychological consequences for women are not well established, and those of partners are largely unknown. Furthermore, it is unclear what factors increase the risk for developing serious psychological symptoms. A range of potential risk factors have been identified, but remain under-researched and have not been rigorously studied. According to Cognitive Behavioural Theory, it is possible that cognitions surrounding the loss may be a particularly relevant risk factor. Yet this topic has rarely been examined and the studies that have are characterised by major methodological shortcomings. Importantly, partners are rarely included in these studies. This study aimed to determine prevalence rates for grief depression and anxiety over the first three and a half months after EPL. It also investigated cognitions after EPL through the Common-Sense Model of Illness Representation, and their link with grief, depression and anxiety symptoms. This study included 28 male partners and 68 women diagnosed with EPL who attended the Early Pregnancy Assessment Service at the Royal Women’s Hospital in Melbourne, Australia. Participants completed self-report measures two weeks (T1), and three months (T2) post-loss. These included the Perinatal Grief Scale, the Centre for Epidemiological Studies-Depression scale, the State Trait Anxiety Inventory, and the Illness Perception Questionnaire-Revised. Results showed that the prevalence of grief, depression and anxiety symptoms for women at T1 were 20.6%, 54.4%, and 52.9%, respectively. For partners, the prevalence rates were 0% for grief, 32.1% for depression, and 25% for anxiety. These rates decreased by T2. Illness perceptions were found to significantly predict grief, depression and anxiety. Unexpectedly, it was often better perceptions of the loss that predicted worse psychological outcomes. These findings provide new information about the experience of EPL and suggest that critical timing for assessment and treatment would be within the first 3 months after EPL. Treatment options, particularly in terms of grief theories presented in the introduction, are discussed. Considering the surprising results and that this is the first study to examine illness perceptions among this sample, replication of these results is needed.
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    The SENSE Study (Sleep and Education: learning New Skills Early): long-term outcomes of a randomised controlled trial of a cognitive-behavioural and mindfulness-based group sleep intervention to prevent depression and improve anxiety in at-risk adolescents
    Raniti, Monika Bianca ( 2019)
    Objective: Depression is one of the most common and debilitating mental health problems and its incidence dramatically increases during adolescence. Accumulating evidence suggests that adolescent depression can be prevented with psychosocial interventions, but there is still insufficient evidence to support their widespread implementation. Notably, there is a need for randomised controlled trials of novel interventions that are delivered to community-based adolescents identified to be at-risk for developing depression (i.e., targeted prevention) rather than the general adolescent population (i.e., universal prevention). Improving sleep represents a promising and innovative therapeutic target for the prevention of adolescent depression. Not only are sleep problems, including insufficient and poor-quality sleep, common during adolescence, they also tend to precipitate the onset of depression. Further, sleep interventions may be especially effective if they are delivered to adolescents experiencing anxiety. Anxiety, particularly generalised anxiety, and sleep problems often co-occur, and anxiety is also a risk factor for the development of depression. Evidence from a small but growing number of studies indicates that multicomponent cognitive-behavioural and mindfulness-based sleep interventions can improve sleep in adolescent samples. However, few studies have investigated depression and anxiety outcomes, particularly using randomised controlled designs, active control comparison conditions, extended follow-up periods, a multi-method assessment of sleep (i.e., subjective and objective measures) and mental health (i.e., diagnosis and symptoms) outcomes, and in community-based samples. Notably, no randomised controlled trial has investigated whether a sleep intervention can prevent the first onset of major depressive disorder (MDD) in adolescents. The current study was designed to address these gaps in the literature. The primary aim of the study was to investigate the long-term efficacy of a seven-week cognitive-behavioural and mindfulness-based group sleep intervention for the targeted prevention of first onset MDD and improvement of depressive symptoms over a two-year follow-up period in community-based adolescents experiencing concurrent high levels of anxiety symptoms and sleep problems (i.e., ‘at-risk’ for depression). Given the association between sleep and anxiety, notably generalised anxiety disorder (GAD), and dearth of adolescent sleep intervention studies investigating anxiety outcomes, the secondary and exploratory aim of the study was to investigate the long-term efficacy of the sleep intervention for preventing the incidence of GAD and improving anxiety symptoms over a two-year follow-up period. Importantly, the study aimed to demonstrate that any beneficial effects to depression and/or anxiety outcomes occurred via the putative mechanism of improvements to subjective and objective indices of sleep. As best can be determined, the research reported in this thesis represents the only attempt to date to prevent first onset MDD by improving sleep in an adolescent sample, and the only randomised controlled trial of an adolescent sleep intervention to examine anxiety outcomes over a two-year follow-up period. It was predicted that, compared to adolescents allocated to the active control (study skills) intervention, adolescents allocated to the sleep treatment intervention would: show greater improvements in subjective and objective indices of sleep (i.e., reduced sleep onset latency, increased total sleep time, better overall sleep quality, and reduced weekday bedtime intra-individual variability and weekday-to-weekend bedtime shift) immediately following the intervention and over the two-year follow-up period; be less likely to develop first onset MDD during, and would report lower levels of depressive symptoms at, the two-year follow-up (primary outcomes); and would be less likely to develop new onset GAD during, and would report lower levels of anxiety symptoms at, the two-year follow-up (secondary outcomes). Further, it was predicted that any beneficial long-term effects for depression and anxiety outcomes (i.e., lower incidence of MDD or GAD and/or reduction in depressive and anxiety symptoms) would be significantly mediated by improvements in sleep associated with the sleep treatment intervention (i.e., sleep improvements immediately post-intervention and/or over the two-year follow-up period). Methods: Participant recruitment and eligibility assessments occurred from January 2013 to June 2014. A school-based screening (n = 1491) was conducted at 23 secondary schools (14 Government, 4 Catholic, 5 Independent) in metropolitan Melbourne, Australia, to identify community-based adolescents with high levels of self-reported sleeping problems (score > 4 on the Pittsburgh Sleep Quality Index; PSQI) and anxiety symptoms (score > 32 males/ > 38 female on the Spence Children’s Anxiety Scale; SCAS). Consenting participants who met screening criteria (n = 218) completed semi-structured diagnostic clinical interview (Kiddie-Schedule for Affective Disorders and Schizophrenia for school-age children-Present and Lifetime version; K-SADS-PL) at the University of Melbourne, primarily to exclude individuals (n = 30) with a lifetime history of MDD, consistent with the study’s aim to prevent first onset depression. Eligible participants (n = 144) were randomised (1:1 allocation on an individual basis, and conditions were balanced for age, gender and presence or absence of current anxiety disorder at baseline) to either a seven-week, face-to-face, multicomponent cognitive-behavioural and mindfulness-based group sleep improvement treatment intervention (Sleep SENSE; n = 71) or an attention-matched active control study skills intervention (Study SENSE; n = 73). The Sleep SENSE intervention aimed to address common sleep problems including insufficient sleep duration, prolonged sleep onset, and variability in sleep timing, and included anxiety management components to assist with managing anxiety during the pre-sleep period. Mental health and sleep were assessed using: the K-SADS-PL (for MDD and GAD diagnosis); the Center for Epidemiologic Studies-Depression scale (CES-D; depressive symptoms); the SCAS (anxiety symptoms); the PSQI (self-reported sleep onset latency, total sleep time, overall sleep quality); and week-long actigraphy with sleep diary (objective sleep onset latency, total sleep time, weekday bedtime intra-individual variability, and weekday-to-weekend bedtime shift). Assessments occurred on three occasions–pre-intervention, post-intervention, and two-years after the completion of the intervention. All outcome assessments were administered by researchers who were blind to participants’ intervention assignment. Statistical analyses: All analyses used a modified intention-to-treat approach. Specifically, the final analysed sample (n = 122, sleep treatment n = 62, control intervention n = 60; 60% female; M age = 14.5 years, SD = 0.95, range 12.04 to 16.31 years) included participants who were eligible for and started the interventions, including those who dropped out of the interventions or were lost to follow-up (n = 13) but excluded participants who were identified as ineligible after randomisation (n = 2) and those who were randomised but never started the interventions (sleep treatment n = 10, control intervention n = 10). Latent growth curve modelling with multiple mediation analysis was used to test the effect of condition (i.e., sleep treatment or control intervention) on the long-term depression (i.e., presence or absence of MDD diagnosis, and severity of depressive symptoms) and anxiety (i.e., presence or absence of GAD diagnosis, and severity of anxiety symptoms) outcomes via improvements in the seven sleep variables immediately post-intervention (i.e., ‘initial status’ which was centred at the post-intervention time point) and over the two-year follow-up period (i.e., average linear ‘rate of change’ scaled to represent change per year). That is, the latent growth process of a sleep variable (i.e., the latent variables of initial status and rate of change) was used the mediator in the tested models. In total, 28 separate models were estimated using Mplus (Version 7) software using maximum likelihood estimation with robust standard errors. Results: Regarding the primary outcomes, there was no statistical evidence that the sleep treatment intervention improved subjective or objective indices of sleep immediately post-intervention or over the two-year follow-up period, or significantly predicted the presence or absence of major depressive disorder during, or reductions in depressive symptoms at, the two-year follow-up, relative to the active control intervention. Regarding the secondary outcome, the sleep treatment intervention did not significantly predict reductions on anxiety symptoms at two-year follow-up. However, the sleep treatment intervention significantly reduced the conditional odds of having GAD during the two-year follow-up period by a factor of seven on average, relative to the active control intervention, although confidence intervals suggested a small effect. There were no statistically significant indirect effects in any of the model investigated. Regardless of condition, participants’ subjective (B = -1.77, 95% CI [-3.47, -0.07]) and objective (B = -4.53, 95% CI [-7.96, -1.10]) sleep onset latency and subjective total sleep time (B = -0.18, 95% CI [-0.31, -0.05]) decreased over time, and weekday bedtime intra-individual variability increased over time (B = 7.99, 95% CI [2.11, 13.86]). In addition, poorer subjective sleep quality (B = 1.46, 95% CI [0.38, 2.54]) and less objective total sleep time (B = -3.31, 95% CI [-6.33, -0.28]) immediately post-intervention predicted depressive symptoms at two-year follow-up, and reductions in weekday bedtime intra-individual variability over time were associated with a decreased likelihood of GAD during the two-year follow-up (B = -0.52, 95% CI [-0.86, -0.18]). Conclusions: Together, the findings do not support the long-term efficacy of a targeted multicomponent cognitive-behavioural and mindfulness-based group sleep intervention for the improvement of sleep problems and prevention of first onset major depressive disorder in a community-based sample of at-risk adolescents. However, they tentatively suggest that anxiety may be more responsive to the sleep intervention than depression. In the context of a robust study design, the findings are hypothesis-generating and raise important considerations for the design of future clinical trials investigating the role of adolescent sleep interventions on emerging psychopathology. Funding: Australian National Health and Medical Research Council Grant (APP1027076). Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN12612001177842; prospectively registered on 6th November 2012).