Melbourne School of Psychological Sciences - Theses
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ItemThe role of biological stress and inflammation in sleep and mental health: a longitudinal perspective among at-risk adolescentsLandau, Elizabeth Rebecca ( 2018)Objective: A healthy functioning body relies in part on a delicate balance between the immune and neuroendocrine (or immuno-endocrine) systems. Sleep disturbance, anxiety, and depression have each been associated with disruptions to the immuno-endocrine system. Recent literature also suggests that dysregulations of the immuno-endocrine system may precipitate sleep disturbance and mental health issues, suggesting a bi-directional role for immuno-endocrine functioning in sleep and mental health. Poor sleep, mental ill-health, and disturbed immuno-endocrine functioning have each been linked to a range of psychosocial, psychiatric, and medical comorbidities including risk for stroke, diabetes, and cardiovascular disease, greater medical expenses, increased substance use, disruptions to interpersonal relationships, poorer vocational outcomes, increased family violence, and more chronic mental and physical health conditions throughout the lifespan. While associations between sleep, mental health, and immuno-endocrine functioning are well- established in adults, less is known about immuno-endocrine functioning in the context of adolescent sleep and mental health, despite high prevalence rates of poor sleep, anxiety, and depression among youth. Further, targeted, preventative treatment interventions for adolescents at-risk of poor sleep, anxiety, and depression may buffer against the progression of mental health issues, as well as immuno-endocrine system dysregulation. However, no study to date has investigated the longitudinal impact of an early-intervention, psychological treatment intervention on biomarkers of immuno-endocrine health in a sample of at-risk-for- depression adolescents. Further, no study with youth has investigated the potential mechanistic role of immuno-endocrine dysregulation in common disease progressions from anxiety issues to depression onset, poor sleep issues to anxiety onset, or poor sleep issues to depression onset. Therefore, the aims of the current thesis were to investigate these gaps in the literature. Method: As part of a larger, multi-center and comprehensive ‘Sleep and Education: learning New Skills Early’ (SENSE) Study, the current thesis investigated the immuno-endocrine functioning of at-risk adolescent participants (n=122, 73 female) in the SENSE Study. The SENSE Study was a two-year, early intervention, randomized-control trial (RCT) researching the impact of a seven-week cognitive-behavioral and mindfulness-based intervention for adolescents who endorsed sleep disturbances and/or anxiety symptoms, known risk factors for the development of depression. The overarching aim of the SENSE Study was to investigate whether a multicomponent sleep intervention, which combined operant conditioning, stimulus control, sleep hygiene psychoeducation, cognitive therapy, and mindfulness-based techniques, would serve as a preventative measure for at-risk adolescents against the development of depression two years post-intervention. Participants were recruited from schools within the Melbourne metropolitan area and invited to participate if they endorsed elevated anxiety and/or poor sleep symptoms, and had no prior history of major depression. At baseline (Time 1; T1) participants (aged 12 to 16 years, mean aged 12.71 years) provided saliva samples across two consecutive days and completed a range of sleep and mood assessments including semi- structured mental health clinical diagnostic interviews, self-report questionnaires, and wrist- actigraphy (an objective measurement of sleep). Participants were randomized into either a seven-week sleep treatment intervention (n=63) or an active study skills control intervention (n=59). Participants completed the same assessments (excepting saliva sample collection) at post-intervention (Time 2; T2), and were assessed again (including saliva sample collection) at two-years post-intervention (Time 3; T3) when participants were aged between 14 and 18 years (mean aged 16.82 years). Thus, immuno-endocrine data was collected at T1 and T3. The current thesis investigated several cross-sectional and longitudinal associations among measures of sleep and mental health with diurnal levels of salivary C-reactive protein (CRP) and cortisol, biomarkers representative of overall systemic functioning of the immune system (CRP) and the neuroendocrine system (cortisol). This project was also the first to use the cortisol to CRP ratio as a measure of inter-system immuno-endocrine organization in the context of sleep and mental health among a sample of youth and in a longitudinal setting. First, for cross-sectional analyses, it was predicted that greater sleep disturbance and mental health issues would be associated with greater disruptions to the immuno-endocrine system (as indexed by higher morning and evening levels of CRP, lower morning and higher evening levels of cortisol, and less homeostatic cortisol to CRP ratio levels). Second, it was predicted that compared to participants in the control intervention, participants in the treatment intervention would display healthier immuno-endocrine functioning at two-year follow-up. Third, it was predicted that dysregulated immuno-endocrine functioning would aid in the progression of 1) anxiety issues to depression onset, 2) poor sleep issues to anxiety onset, and 3) poor sleep issues to depression onset. Finally, it was predicted that sex would be a moderator in all analyses. Results: First, cross-sectional multivariate regression analyses indicated that participants who self-reported longer sleep onset latency (the period of time attempting to fall asleep) at T1 had more blunted morning cortisol levels at T1, even when controlling for common covariates used in the literature. Sex did not moderate this relationship. Second, one-way analyses of covariance (ANCOVA) were conducted to investigate treatment effects on salivary levels of CRP and cortisol, which revealed no statistically significant effects of treatment conditions on biomarkers measured at T3. Two-way ANCOVAs investigating the effect of treatment and sex were also not significant. Third, longitudinal analyses revealed that participants with greater bedtime variability at T1 were less likely to experience depressive symptoms at T2, and more likely to experience a clinical anxiety episode by T3, although levels of CRP and cortisol did not mediate these paths. Finally, participants with an anxiety disorder at T1 were 4.58 times at risk of developing a depressive disorder by T3, although levels of CRP and cortisol did not mediate this path. Sex did not moderate any longitudinal analysis. However, a higher T1 cortisol to CRP ratio (indicative of elevated levels of cortisol relative to attenuated levels of CRP) significantly predicted the onset of a first-ever depressive disorder by T3, even when controlling for T1 depressive symptoms. Conclusion: The current study adds to the literature on links between sleep, mental health, and immuno-endocrine functioning in youth, a relatively new area of research. Results highlight important methodological considerations that future treatment studies should incorporate, considerations which may encourage benefits to the adolescent immuno-endocrine system. The continuation of immuno-endocrine biomarker assessment among youth populations will advance the knowledge of the potential biological underpinnings of sleep disturbance and poor mental health. Refinement of treatment interventions may pave the way for such underlying mechanisms to be harnessed and recruited along the path to treatment outcome goals. Moreover, that perceived sleep onset latency but not objective sleep onset latency was associated with more blunted cortisol levels suggests that interventions designed to target negative or inaccurate assessments of sleep may buffer against neuroendocrine health consequences. Lastly, the finding that adolescents with a more disorganized immuno- endocrine system (i.e., a higher cortisol to CRP ratio) were more at risk of developing depression is novel, and suggests that the cortisol to CRP ratio could serve as a disease risk biomarker for first-onset depression. Early identification of individuals at high risk of depression may prevent medical and psychiatric comorbidities throughout the lifespan.
ItemThe SENSE study (Sleep and Education: learning New Skills Early): postintervention effects of a randomised controlled trial of a cognitive-behavioural and mindfulness-based group sleep improvement intervention among at-risk adolescentsBlake, Matthew John ( 2016)Objective: There is growing recognition that many adolescents obtain insufficient and/or poor quality sleep. Sleep problems are also a major risk factor for the emergence of mental health problems in adolescence. However, few studies have examined disturbed sleep as a potential mechanism in the treatment and prevention of mental health problems among adolescents. Adolescent sleep problems can be treated using a range of approaches. School-based sleep education programs, which are typically delivered to whole school classes, have been shown to have little impact on sleep behaviour or mental health. Cognitive-behavioural and mindfulness-based sleep programs, which are typically delivered to at-risk or already symptomatic adolescents, have been shown to be more effective in improving sleep and emotional distress, but studies evaluating their effectiveness have been limited in several ways, including small sample sizes and inadequate/lack of control groups. We conducted a systematic review and meta-analysis examining the efficacy of cognitive-behavioural sleep interventions among adolescents. Searches of PubMed, PsycINFO, CENTRAL, EMBASE, and MEDLINE were performed from inception to 1 May 2016. Eight trials were selected (n=234, mean age=15.24 years; female=63.18%). Main outcomes were subjective (sleep diary/questionnaire) and objective (actigraphy) total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), and wake after sleep onset (WASO). There was a small number of randomised controlled trials (RCTs; n=3), and a high risk of bias across the RCTs; therefore within sleep condition meta-analyses were examined. At post-intervention, subjective TST improved by 29.47 minutes (95% CI = 17.18, 41.75), SOL by 21.44 minutes (95% CI = -30.78, -12.11), SE by 5.34% (95% CI = 2.64, 8.04), and WASO by a medium effect size (d = 0.59 [95% CI = 0.36, 0.82). Objective SOL improved by 16.15 minutes (95% CI = -26.13, -6.17), and SE by 2.82% (95% CI = 0.58, 5.07). Global sleep quality, daytime sleepiness, depression, and anxiety also improved. Gains were generally maintained over time. Our meta-analysis provides preliminary evidence that cognitive-behavioural sleep interventions are an effective treatment for adolescent sleep problems, producing clinically meaningful responses within active treatment conditions. Their efficacy is maintained over time, and results in significant alleviation of sleep problems and improvement in functional outcomes. However, further large-scale, high-quality RCTs are needed to confirm these findings. The aim of this thesis was to investigate the post-intervention effects of a cognitive-behavioural/mindfulness-based group sleep intervention on sleep, mental health, and cognitive style among at-risk adolescents. The study went beyond simply measuring treatment outcomes to also evaluate mechanisms of change. Based on the behavioural, cognitive, hyperarousal, and transdiagnostic models of insomnia, a number of specific mediators were hypothesised to account for therapeutic change in cognitive-behavioural and mindfulness-based sleep interventions for adolescents, including earlier bedtimes, more consistent bedtimes, increased sleep hygiene awareness, and decreased dysfunctional beliefs and attitudes about sleep, worry, rumination, pre-sleep arousal, anxiety, and depression. Method: A RCT was conducted across Victorian secondary schools in Melbourne, Australia. Adolescents (aged 12-17 years) were recruited using a two-stage procedure, consisting of an in-school screening (n=1491) followed by a diagnostic interview for those meeting screening criteria (n=218), to identify students with high levels of anxiety and sleeping difficulties, but without past or current major depressive disorder (n=144). Eligible participants were randomised into either a sleep improvement intervention (‘Sleep SENSE’) or an active control ‘study skills’ intervention (‘Study SENSE’). One hundred twenty three participants began the interventions (Female=60%; Mean Age=14.48, SD=0.95), with 60 in the sleep condition and 63 in the control condition. All participants were required to complete a battery of mood, sleep and cognitive style questionnaires, seven-days of wrist actigraphy (an objective measurement of sleep), and sleep diary entry at pre-and-post intervention. Results: The sleep intervention condition was associated with significantly greater improvements in subjective sleep (global sleep quality, sleep onset latency, daytime sleepiness), objective sleep onset latency, anxiety, pre-sleep arousal, and sleep knowledge compared with the control intervention condition, with small-medium effect sizes. Parallel multiple mediation models showed that there were bidirectional relationships between improvements in subjective sleep quality and pre-sleep arousal/global anxiety. Conclusion: The SENSE study is an efficacy trial of a selective group-based sleep intervention for the treatment and prevention of sleep and mental health problems among at-risk adolescents experiencing both sleep and anxiety disturbance. The study provides evidence, using a methodologically rigorous design, including an active control comparison condition, that a multi-component group sleep intervention that includes cognitive-behavioural and mindfulness-based therapies, can improve wakefulness in bed variables, daytime dysfunction, anxiety, pre-sleep arousal, and sleep knowledge among at-risk adolescents. The results also provide evidence that pre-sleep arousal and anxiety are particularly important for adolescents’ perceived sleep quality, and should be key targets for new treatments of adolescent sleep problems. Public Health Significance: Given the high prevalence of adolescent sleep and internalising problems, the implications of an effective adolescent sleep intervention for clinical practice and public policy are potentially significant. However, changing sleep behaviour, especially objective measures of sleep, in this age group, has been challenging. This thesis shows that the Sleep-SENSE program can improve objective and subjective indices of sleep, as well as anxiety symptoms, when compared to an active control intervention. The results also showed that reductions in pre-sleep hyperarousal represent a key psychophysiological mechanism for therapeutic improvements in subjective sleep problems among anxious adolescents, and that cognitive behavioural and mindfulness-based sleep interventions should be directed towards adolescents with vulnerability for hyperarousal. Sleep SENSE is one of the only interventions demonstrated to be efficacious in improving sleep and mental health amongst vulnerable adolescents. Furthermore, the program is likely to be cost-effective - it involves a simple screening process and a group intervention format - and could be disseminated to a wide range of clinical and non-clinical settings in primary care, mental health, adolescent health and sleep medicine, and may assist in the treatment and prevention of adolescent sleep and mental health problems. The intervention also lends itself to flexible modes of delivery (e.g., non-specialist practitioners, group settings, individual settings, school-based, internet and other e-health modes of delivery), further enhancing its translational potential.
ItemGetting to the heart of teen depression: the relationship between depression and cardiovascular risk in adolescents during wakefulness and sleepWaloszek, Joanna Maria ( 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.