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ItemThe 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 adolescentsRaniti, 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).
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.
ItemSleep, mood, and cognitive vulnerability in adolescents: a naturalistic study over restricted and extended sleep opportunitiesBEI, BEI ( 2013)Introduction: It is well established that for adolescents, school days are associated with sleep restriction, and that insufficient sleep has been linked to mood disturbances. This longitudinal study assessed sleep, mood, and life stress over the school term and vacation periods with restricted and extended sleep opportunities. The relationships between objective and subjective sleep, as well as between sleep and mood were examined. A cognitive model was proposed and tested to assess whether sleep-specific (i.e., dysfunctional beliefs and attitudes about sleep) and global (i.e., dysfunctional attitudes) cognitive vulnerabilities played a role in these relationships. Methods: One-hundred and forty-six adolescents (47.3% male) aged 16.2+/-1.0 years (M+/-SD) from the general community wore an actigraph continuously for four weeks: the last week of a school term (Time-E), the following two-week vacation (Time-V), and the first week of the next term (Time-S). Social demographic information, chronotype, and cognitive vulnerabilities were assessed at Time-E. Subjective sleep, symptoms of depression, anxiety, and life stress were repeatedly measured at Time-E, Time-V, Time-S, and the middle of the subsequent school term. Regression analyses were used to explore the relationship between sleep and mood, and structural equation modelling was used to examine changes of variables over time, as well as the moderating roles of cognitive vulnerabilities. Results: Compared with school days, sleep during the vacation was characterized by later timing, longer duration, lower quality and greater variability. Daily changes in actigraphy- measured sleep over the vacation period showed linear delays in sleep timing throughout the vacation, while changes in time-in-bed were non-significant. The first vacation week was characterized by a linear decrease in total sleep time and sleep quality, and these changes stabilized during the second vacation week. Compared to vacations, school terms were associated with higher symptoms of depression, anxiety, and life stress. Poorer sleep quality, particularly poorer subjective perception of sleep quality, was significantly associated with higher symptoms of depression and anxiety. Sleep- specific cognitive vulnerability moderated the relationship between objective and subjective sleep onset latency during extended but not restricted sleep opportunity. After controlling for life stress, global cognitive vulnerability played different moderating roles in the relationship between subjective sleep and mood over school term and vacation periods. Higher global cognitive vulnerability was associated with a stronger relationship between subjective sleep and symptoms of anxiety (but not depression) during the school term, as well as with a stronger relationship between subjective sleep and symptoms of depression (but not anxiety) during the vacation period. Conclusion: Sleep, mood, and life stress changed markedly over the school term and vacation periods. Changes in sleep over the vacation suggested that the recovery from school- related sleep restriction was completed within two weeks’ extended sleep opportunity, and the average sleep duration over this period suggested that sleep requirements in adolescence may be less than conventionally described in the media and in the scientific literature. Cognitive vulnerabilities played important roles in the relationship between sleep and mood. Adolescents with higher cognitive vulnerability might be more emotionally vulnerable towards school-related sleep restriction. These findings have important implications for future studies, as well as practical implications for policies and interventions designed to improve adolescents’ wellbeing.
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.