Efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction for Depression Symptoms and Sleep-Wake Disruption in Older and Younger Adults: Secondary Age-Stratified Analysis of a Randomized Controlled Trial.

OBJECTIVE: Perform a secondary analysis examining the efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for depression symptom responses, and explore changes in potential target mechanisms. DESIGN: Secondary analysis of a randomized controlled trial with convenience age subsamples (younger (20-49 year; n = 52) versus and older (50-71 years; n = 35)). SETTING: Community mental health clinics. PARTICIPANTS: Eighty-seven adults with serious mental illness. INTERVENTION: TranS-C versus treatment as usual (TAU). MEASUREMENTS: Outcomes were depression symptoms (Quick Inventory of Depression Symptoms), insomnia symptoms (Insomnia Severity Index), and objective sleep-wake rhythm measures (interdaily stability and relative amplitude). RESULTS: Depression response rates (≥50% symptom reductions) were higher in the TranS-C (35.0%) than the TAU (8.8%) group 6-months postintervention (χ2 = 10.3, p = 0.001). There was a medium effect of TranS-C versus TAU on depression symptoms 6-months postintervention (Cohen's d = -0.40, 95% confidence interval (CI): -0.81, 0.01). In both age groups, there were large treatment effects on insomnia symptoms post-treatment (Cohen's d >0.90). In the older subsample, there were additionally medium treatment effects on post-treatment interdaily stability (Cohen's d = 0.60, 95% CI: -0.11, 1.61). Post-treatment reductions in insomnia symptoms correlated with depression symptom reduction 6-months later in the younger subsample (Spearman rho = 0.59, n = 20, p = 0.008). In older adults, postintervention increases in interdaily stability correlated with depression symptom reductions 6-months later (Spearman rho = -0.52, n = 15, p = 0.049). CONCLUSION: Confirmatory trials are needed, given the low age-specific sample sizes here, to determine if TranS -C's produces durable depression responses by increasing sleep-wake rhythm stability in older adults and improving insomnia symptoms in younger adults. BRIEF ARTICLE SUMMARY: The authors evaluated preliminary efficacy of a behavioral intervention that targets sleep/sleep-wake rhythms, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C), for depression symptoms in people with serious mental illness. TranS-C was associated with higher depression response rates than treatment as usual 6-months postintervention. The degree of depression symptom response 6-months later was related to the degree of treatment phase improvements in interdaily stability (in older adults) and reduction in insomnia severity (in younger adults). A pragmatic nonpharmacologic intervention, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction, has preliminary efficacy for improving sleep-wake factors and depression symptoms.

Circadian rhythms and disorders of the timing of sleep.

The daily alternation between sleep and wakefulness is one of the most dominant features of our lives and is a manifestation of the intrinsic 24 h rhythmicity underlying almost every aspect of our physiology. Circadian rhythms are generated by networks of molecular oscillators in the brain and peripheral tissues that interact with environmental and behavioural cycles to promote the occurrence of sleep during the environmental night. This alignment is often disturbed, however, by contemporary changes to our living environments, work or social schedules, patterns of light exposure, and biological factors, with consequences not only for sleep timing but also for our physical and mental health. Characterised by undesirable or irregular timing of sleep and wakefulness, in this Series paper we critically examine the existing categories of circadian rhythm sleep-wake disorders and the role of the circadian system in their development. We emphasise how not all disruption to daily rhythms is driven solely by an underlying circadian disturbance, and take a broader, dimensional approach to explore how circadian rhythms and sleep homoeostasis interact with behavioural and environmental factors. Very few high-quality epidemiological and intervention studies exist, and wider recognition and treatment of sleep timing disorders are currently hindered by a scarcity of accessible and objective tools for quantifying sleep and circadian physiology and environmental variables. We therefore assess emerging wearable technology, transcriptomics, and mathematical modelling approaches that promise to accelerate the integration of our knowledge in sleep and circadian science into improved human health.

Report from a randomized control trial: improved alignment between circadian biology and sleep-wake behavior as a mechanism of depression symptom improvement in evening-type adolescents with depressive symptoms.

STUDY OBJECTIVES: An evening circadian preference is common among adolescents. It is characterized by a behavioral predilection for later sleep and wake timing and is associated with higher rates of Major Depressive Disorder (MDD). The present study aims to (a) test the effectiveness of a cognitive behavioral sleep intervention (Transdiagnostic Sleep and Circadian Intervention; TranS-C) in a sample of adolescents with an evening circadian preference and clinically significant depressive symptoms and (b) evaluate improved alignment between circadian biology and sleep-wake behavior as a potential mechanism in the relationship between sleep and depression symptom improvement. METHODS: Adolescents with an evening circadian preference and clinically significant depressive symptoms were randomized to receive TranS-C (n = 24) or a psychoeducation condition (PE; n = 18). Alignment between circadian biology and sleep-wake behavior was measured using objective biological measurement. Measures of sleep and circadian rhythm were taken at pre- and posttreatment, and depression symptoms were measured at pre- and posttreatment and 6- and 12-month follow-up. RESULTS: Mixed effects modeling revealed that compared with an active control condition, TranS-C resulted in a significant reduction in MDD severity at 12-month follow-up. A MacArthur mediation analysis conducted to explore alignment between circadian biology and sleep-wake behavior as a mediator of depression severity reduction through 12-month follow-up revealed a significant interaction between change in alignment between circadian biology and sleep-wake behavior and treatment arm, indicating that improved alignment between circadian biology and sleep-wake behavior at posttreatment was associated with improvements in depression outcomes at 12-month follow-up under the treatment condition. CONCLUSIONS: These results provide novel evidence for improved alignment between circadian biology and sleep-wake behavior as a specific mechanism of depression improvement, provide key clues into the complex relationship between sleep and depression, and have significant clinical implications for adolescents with depression.

Digital cognitive behaviour therapy for insomnia in individuals with self-reported insomnia and chronic fatigue: A secondary analysis of a large scale randomized controlled trial.

Insomnia is associated with fatigue, but it is unclear whether response to cognitive behaviour therapy for insomnia is altered in individuals with co-occurring symptoms of insomnia and chronic fatigue. This is a secondary analysis using data from 1717 participants with self-reported insomnia in a community-based randomized controlled trial of digital cognitive behaviour therapy for insomnia compared with patient education. We employed baseline ratings of the Chalder Fatigue Questionnaire to identify participants with more or fewer symptoms of self-reported chronic fatigue (chronic fatigue, n = 592; no chronic fatigue, n = 1125). We used linear mixed models with Insomnia Severity Index, Short Form-12 mental health, Short Form-12 physical health, and the Hospital Anxiety and Depression Scale separately as outcome variables. The main covariates were main effects and interactions for time (baseline versus 9-week follow-up), intervention, and chronic fatigue. Participants with chronic fatigue reported significantly greater improvements following digital cognitive behaviour therapy for insomnia compared with patient education on the Insomnia Severity Index (Cohen's d = 1.36, p < 0.001), Short Form-12 mental health (Cohen's d = 0.19, p = 0.029), and Hospital Anxiety and Depression Scale (Cohen's d = 0.18, p = 0.010). There were no significant differences in the effectiveness of digital cognitive behaviour therapy for insomnia between chronic fatigue and no chronic fatigue participants on any outcome. We conclude that in a large community-based sample of adults with insomnia, co-occurring chronic fatigue did not moderate the effectiveness of digital cognitive behaviour therapy for insomnia on any of the tested outcomes. This may further establish digital cognitive behaviour therapy for insomnia as an adjunctive intervention in individuals with physical and mental disorders.

Transdiagnostic Sleep and Circadian Intervention for Adolescents Plus Text Messaging: Randomized Controlled Trial 12-month Follow-up.

OBJECTIVE: The Transdiagnostic Sleep and Circadian Intervention for Youth (TranS-C) was developed to improve sleep and circadian functioning in adolescents. This study examined the 12-month effects for TranS-C compared with psychoeducation (PE). We also investigated whether a text messaging intervention can promote maintenance of treatment effects. METHOD: At the baseline, adolescents (58% female, average age = 14.8 years) with an eveningness chronotype were randomized to TranS-C (n = 89) or PE (n = 87). At 6-month follow-up, participants were randomized to receive text messages that had repeated treatment information (n = 47), text messages that prompted the recall of treatment information (n = 50), or no text messages (n = 47). RESULTS: Relative to PE, TranS-C was associated with a reduced eveningness (b = 2.06, p = .005, d = 0.29) from the baseline to a 12-month follow-up. TranS-C treatment effects, relative to PE, were augmented by receiving text messages, compared to no text messages, for eveningness from baseline to 12-month follow-up (b = 1.38, p = .008, d = 0.28) and from 6- to 12-month follow-up (b = 1.07, p = .046, d = 0.21). Neither TranS-C nor text messages were significantly associated with other primary outcomes. TranS-C and text messages were significantly associated with improvements on selected secondary sleep and health outcomes through follow-up. CONCLUSIONS: For adolescents with an eveningness chronotype, improved sleep and circadian functioning on selected outcomes were maintained over 12 months for TranS-C compared with PE. Text messages boosted the effects of TranS-C through 12-month follow-up.

Therapist training in treating sleep problems: A survey study of clinical practice.

OBJECTIVES: Mental health care clinicians' training in treating sleep problems was investigated. We examined clinicians' (1) prior training in providing treatment for sleep problems, (2) interest in receiving training in treatment for sleep problems, and (3) perceptions of the importance of treating sleep problems and interest in incorporating sleep treatments into their practices. METHODS: An online survey was completed by 137 clinicians. RESULTS: The majority of clinicians (61.31%) reported receiving prior training in treating sleep problems, most commonly in the form of a workshop and after receiving a graduate degree. Most clinicians reported interest in receiving further training in treating sleep problems. Clinicians reported that the majority (66.67%) of their clients experience sleep problems, yet reported that they address sleep with fewer than half of clients. Addressing sleep in treatment was rated as "somewhat" to "very" important and most clinicians indicated further interest in receiving training in treating sleep. CONCLUSIONS: Mental health care clinicians receive limited training in treating sleep problems. As clinicians are interested in gaining further training to address sleep concerns within their clinical practice, training programs and continuing education programs should consider increasing the amount of programming in sleep treatment and assessment.

Digital cognitive behaviour therapy for insomnia (dCBT-I): Chronotype moderation on intervention outcomes.

Using data from 1721 participants in a community-based randomized control trial of digital cognitive behavioural therapy for insomnia compared with patient education, we employed linear mixed modelling analyses to examine whether chronotype moderated the benefits of digital cognitive behavioural therapy for insomnia on self-reported levels of insomnia severity, fatigue and psychological distress. Baseline self-ratings on the reduced version of the Horne-Östberg Morningness-Eveningness Questionnaire were used to categorize the sample into three chronotypes: morning type (n = 345; 20%); intermediate type (n = 843; 49%); and evening type (n = 524; 30%). Insomnia Severity Index, Chalder Fatigue Questionnaire, and Hospital Anxiety and Depression Scale were assessed pre- and post-intervention (9 weeks). For individuals with self-reported morning or intermediate chronotypes, digital cognitive behavioural therapy for insomnia was superior to patient education on all ratings (Insomnia Severity Index, Chalder Fatigue Questionnaire, and Hospital Anxiety and Depression Scale) at follow-up (p-values ≤ 0.05). For individuals with self-reported evening chronotype, digital cognitive behavioural therapy for insomnia was superior to patient education for Insomnia Severity Index and Chalder Fatigue Questionnaire, but not on the Hospital Anxiety and Depression Scale (p = 0.139). There were significant differences in the treatment effects between the three chronotypes on the Insomnia Severity Index (p = 0.023) estimated difference between evening and morning type of -1.70, 95% confidence interval: -2.96 to -0.45, p = 0.008, and estimated difference between evening and intermediate type -1.53, 95% confidence interval: -3.04 to -0.03, p = 0.046. There were no significant differences in the treatment effects between the three chronotypes on the Chalder Fatigue Questionnaire (p = 0.488) or the Hospital Anxiety and Depression Scale (p = 0.536). We conclude that self-reported chronotype moderates the effects of digital cognitive behavioural therapy for insomnia on insomnia severity, but not on psychological distress or fatigue.

Sleep problems among adolescents within child and adolescent mental health services. An epidemiological study with registry linkage.

Sleep problems are prevalent among adolescents, especially among those diagnosed with mental health disorders. There is insufficient knowledge about sleep among adolescents within child and adolescent mental health services (CAMHS) in comparison to the general population. The data are drawn from the youth@hordaland study, a large population-based study conducted in 2012, linked to the Norwegian Patient Registry (NPR) (n = 9077). Psychiatric disorders were based on clinical diagnoses from the NPR, while insomnia, delayed sleep-wake-phase disorder (DSWPD), and other sleep problems/patterns were assessed by self-report questionnaires from youth@hordaland. The prevalence of diagnosed sleep disorders among adolescents seeking mental health services was 0.6%, yielding an estimated prevalence of 0.07% of the population. However, questionnaire-based measurement of insomnia from the youth@hordaland study indicated that insomnia was highly prevalent across disorders in comparison to a reference group of adolescents who were not within mental health care. Insomnia ranged from 29% among adolescents diagnosed with ADHD (PR = 1.79; 95% CI 1.41-2.29) to 48% among adolescents diagnosed with depression (PR = 2.53, 95% CI 2.19-2.92). All diagnostic groups had a mean sleep efficiency below (85%), indicating poor sleep quality. Insomnia, delayed sleep-phase wake disorder, and poor sleep efficiency were confirmed as transdiagnostic sleep problems across psychiatric disorders. In addition, some disorder-specific patterns emerged, such as a higher prevalence of insomnia among adolescents with depression, and DSWPS among adolescents with conduct disorder. This underscores the need for treating sleep problems in CAMHS, and transdiagnostic treatment approaches are warranted.

Sleep problems and depressive symptoms in toddlers and 8-year-old children: A longitudinal study.

Sleep and depression are interlinked throughout the lifespan, but very few studies have examined the directionality of the sleep-depression link in children. The aim of the current study was to prospectively examine the bidirectional association between sleep problems and internalizing problems and depressive symptoms in toddlers and children aged 1.5 and 8 years. Data stem from the large ongoing population-based longitudinal study, the Norwegian Mother, Father and Child Cohort Study, recruited from October 1999 to July 2009. A total of 35,075 children were included. Information on sleep duration, nocturnal awakenings and internalizing problems (Child Behaviour Checklist) was provided by the mothers at 1.5 years, whereas data on sleep duration and depressive symptoms (Short Mood and Feelings Questionnaire) were provided by the mothers when the children were 8 years old. Odds ratios (ORs) were calculated using logistic regression analyses. After accounting for previous internalizing problems, short sleep duration (≤10 hr) and frequent (≥3) nightly awakenings at 1.5 years predicted the development of depressive symptoms at 8 years of age (adjusted OR = 1.28; 95% confidence interval [CI] 1.08-1.51, and adjusted OR = 1.27, 95% CI 1.08-1.50, respectively). Also, internalizing problems at 1.5 years predicted onset of later short sleep duration (adjusted OR = 1.83, 95% CI 1.32-2.54) after accounting for early sleep problems. This prospective study demonstrated a bidirectional association between sleep and internalizing/depressive symptoms from toddlerhood to middle childhood. Intervention studies are needed to examine whether targeting either of these problems at this early age may prevent onset of the other.

The Impact of Television, Electronic Games, and Social Technology Use on Sleep and Health in Adolescents with an Evening Circadian Preference.

There are mixed findings when examining if technology use is harmful for adolescent sleep and health. This study builds on these mixed findings by examining the association between technology use with sleep and health in a high-risk group of adolescents. Adolescents with an evening circadian preference (N = 176; 58% female, mean age = 14.77, age range = 10-18) completed measures over one week. Sleep was measured via actigraphy. Technology use and health were measured using ecological momentary assessment. Technology use was associated with an increase in sleep onset latency; with better emotional, social, cognitive, and physical health; and with worse behavioral health. This study offers support for technology use having some benefits and expands research on technology use to adolescents with an evening circadian preference.

A transdiagnostic sleep and circadian intervention for adolescents: six-month follow-up of a randomized controlled trial.

BACKGROUND: This study examined the 6-month follow-up outcomes of the Transdiagnostic Sleep and Circadian Intervention (TranS-C), compared to Psychoeducation about sleep and health (PE). METHODS: Adolescents (mean [SD] = 14.77 [1.84] years) with eveningness chronotype and "at-risk" in at least one of five health domains were randomized to receive TranS-C (n = 89) or PE (n = 87) at a university-based clinic. Primary outcomes were average weeknight total sleep time and bedtime calculated from sleep diary, a questionnaire measure of circadian preference, and composite risks in five health domains. Secondary outcomes were selected sleep diary indices, sleepiness, and self- and parent-reported sleep, parent-reported risks in five health domains. RESULTS: Relative to PE, TranS-C showed treatment effects through 6-month follow-up on only one primary outcome; namely eveningness circadian preference. TranS-C also showed treatment effects on two sleep and circadian secondary outcomes, including the Pittsburgh Sleep Quality Index and sleep-diary measured weeknight-weekend discrepancy in wakeup time. TranS-C did not show treatment effects on self-report or parent-report composite risks in five health domains. PE showed benefit, relative to TranS-C, from posttreatment to 6-month follow-up for reducing parent-reported behavioral health risk (secondary outcome). CONCLUSIONS: In at-risk adolescents, the evidence supports the TranS-C treatment effects over six months on improving sleep and circadian functioning on selected outcomes but not on reducing risk in five health domains.

Sleep restriction alters children's positive emotional responses, but effects are moderated by anxiety.

BACKGROUND: An abundance of cross-sectional research links inadequate sleep with poor emotional health, but experimental studies in children are rare. Further, the impact of sleep loss is not uniform across individuals and pre-existing anxiety might potentiate the effects of poor sleep on children's emotional functioning. METHODS: A sample of 53 children (7-11 years, M = 9.0; 56% female) completed multimodal, assessments in the laboratory when rested and after two nights of sleep restriction (7 and 6 hr in bed, respectively). Sleep was monitored with polysomnography and actigraphy. Subjective reports of affect and arousal, psychophysiological reactivity and regulation, and objective emotional expression were examined during two emotional processing tasks, including one where children were asked to suppress their emotional responses. RESULTS: After sleep restriction, deleterious alterations were observed in children's affect, emotional arousal, facial expressions, and emotion regulation. These effects were primarily detected in response to positive emotional stimuli. The presence of anxiety symptoms moderated most alterations in emotional processing observed after sleep restriction. CONCLUSIONS: Results suggest inadequate sleep preferentially impacts positive compared to negative emotion in prepubertal children and that pre-existing anxiety symptoms amplify these effects. Implications for children's everyday socioemotional lives and long-term affective risk are highlighted.

Addressing the Challenges of Recruitment and Retention in Sleep and Circadian Clinical Trials.

Objective/Background: Sleep and circadian disorders are prevalent worldwide and frequently comorbid with physical and mental illnesses. Thus, recruiting and retaining samples for sleep and circadian research are high priorities. The aims of this paper are to highlight barriers to recruitment and retention for participants with sleep or circadian dysfunction, and to share strategies used across two randomized controlled trials (RCTs) testing the efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) to address these challenges. Participants: The first RCT recruited 176 adolescents with an evening circadian chronotype, who were at risk in at least one of five health domains: behavioral, cognitive, emotional, physical, and social. The second RCT recruited 121 low-income, racial or ethnic minority adults diagnosed with severe mental illness (SMI) and comorbid sleep or circadian dysfunction. Methods: The current study examined participant, environment, and research factors that impacted recruitment and retention of participants with sleep or circadian dysfunction, and identified strategies to enhance recruitment and retention. Results: Strategies used to recruit participants included community-based recruiting, reducing stigma, and alleviating burdensome sleep data collection. Strategies used to retain participants in our studies included flexible scheduling, mitigating participant barriers, building rapport with participants through empathic and positive interactions, creative problem solving, consulting participant networks, and utilizing incentives and other positive engagement tools. Conclusion: Both at-risk adolescents and low-income, minority adults with comorbid SMI and sleep or circadian dysfunction experience significant barriers to research participation. Recruitment and retention strategies were creatively tailored to meet the unique barriers of these diverse populations.

Psychometric properties of the Insomnia Catastrophizing Scale (ICS) in a large community sample.

The purpose was to investigate the psychometric properties of the Insomnia Catastrophizing Scale (ICS) including factorial validity and internal consistency as well as discriminative and convergent validity. Associations with sleep parameters and daytime impairment are also examined. Drawn from a randomly selected sample of the general population, 1615 participants completed a survey on insomnia-related nighttime and daytime symptoms, health outcomes and psychological processes, including the ICS. A one-factor solution was supported for both the nighttime catastrophizing (11 items) and daytime catastrophizing (6 items) subscales. Both subscales displayed high internal consistencies (α > 0.90) and accounted for 59.1-70.1% of the variance. The insomnia disorder group had significantly higher scores than participants without insomnia on the two subscales and on the individual items. Cutoffs were established for both subscales with acceptable sensitivity and specificity. Both subscales displayed adequate convergent validity with measures indexing worry, cognitive pre-sleep arousal and anxiety. The two subscales were also significantly associated with nighttime and daytime insomnia symptoms. The ICS is a reliable and valid scale for the assessment of insomnia-related catastrophizing. Future research is needed to examine the test-retest reliability and treatment sensitivity of the ICS.

Sleep patterns and insomnia in young adults: A national survey of Norwegian university students.

The aim of this study was to describe sleep patterns and rate of insomnia according to diagnostic criteria in college and university students, as well as to examine potential changes in sleep problems from 2010 to 2018. Data stemmed from a national student health survey from 2018 for higher education in Norway (the SHoT study), which invited all 162,512 fulltime students in Norway. A total of 50,054 students (69.1% women) aged 18-35 years were included, yielding a response rate of 30.8%. Sleep parameters, reported separately for weekdays and weekends, included calculations of bedtime, rise time, sleep duration, sleep-onset latency, wake after sleep onset, sleep need and sleep deficit. Insomnia was defined according to the Diagnostic and Statistical Manual of Mental Disorders (5th edn) criteria. For the trend analysis, we used one item measuring difficulties initiating and/or maintaining sleep, over three time points (2010, 2014 and 2018). The results from 2018 showed large weekday-weekend differences across most sleep parameters. Both male and female students obtained a mean sleep duration in the lower end of the normal range on weekdays (7:24 hr), but met their own sleep need and sleep recommendations at weekends (8:25 hr). The overall prevalence of insomnia was 34.2% in women and 22.2% in men. There was a substantial increase in sleep problems from 2010 (22.6%) to 2018 (30.5%), which was especially pronounced in women. We conclude that sleep problems are both prevalent and increasing among students. This warrants attention as a public health problem in this population.

Sleep, Circadian Rhythms, and Risk Across Health Domains in Adolescents With an Evening Circadian Preference.

Sleep and circadian rhythm changes during adolescence contribute to increased risk across emotional, behavioral, cognitive, social, and physical health domains. This study examines if sleep and dim light melatonin onset (DLMO) are related to greater risk in these 5 health domains. Participants were 163 (93 female, age = 14.7 years) adolescents with an evening circadian preference from a study funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Sleep and circadian measures included weekday total sleep time (TST), bedtime, and shut-eye time assessed via sleep diary, the Children's Morningness-Eveningness Preferences scale, and DLMO. Health domains included self-reported emotional, cognitive, behavioral, social, and physical health. Later DLMO was significantly associated with shorter weekday TST, later weekday bedtime, and later weekday shut-eye time, as well as lower risk in the behavioral domain. At the trend level, later DLMO was related to fewer physical health problems. Earlier DLMO combined with a later bedtime, later shut-eye time, or shorter TST predicted greater risk in the cognitive domain. Later DLMO and shorter TST or a later bedtime predicted worse physical health. DLMO timing was not related to the emotional or social domain. There is evidence that a discrepancy between sleep behaviors and the endogenous circadian rhythm may be related to risk in the cognitive domain for adolescents with an evening circadian preference. Preliminary evidence also indicated that a delayed DLMO and shorter TST or a later bedtime may be related to vulnerability to physical health risk.

Anxiety Treatment and Targeted Sleep Enhancement to Address Sleep Disturbance in Pre/Early Adolescents with Anxiety.

Sleep disturbance is prevalent in anxious youth and prospectively predicts poor emotional adjustment in adolescence. Study 1 examined whether anxiety treatment improves subjective and objective sleep disturbance in anxious youth. Study 2 examined whether a sleep intervention called Sleeping TIGERS can further improve sleep following anxiety treatment. Study 1 examined 133 youth (ages 9-14; 56% female; 11% ethnic/racial minority) with generalized, social, or separation anxiety over the course of anxiety treatment (cognitive behavioral treatment or client-centered treatment). Sleep-related problems (parent-, child-report) and subjective (diary) and objective (actigraphy) sleep patterns were assessed across treatment in an open trial design. Study 2 included 50 youth (ages 9-14; 68% female; 10% ethnic/racial minority) who continued to report sleep-related problems after anxiety treatment and enrolled in an open trial of Sleeping TIGERS. Pre- and postassessments duplicated Study 1 and included the Focal Interview of Sleep to assess sleep disturbance. Study 1 demonstrated small reductions in sleep problems and improvements in subjective sleep patterns (diary) across anxiety treatment, but outcomes were not deemed clinically significant, and 75% of youth stayed above clinical cutoff. Study 2 showed clinically significant, large reductions in sleep problems and small changes in some subjective sleep patterns (diary). Anxiety treatment improves, but does not resolve, sleep disturbance in peri-pubertal youth, which may portend risk for poor emotional adjustment and mental health. The open trial provides preliminary support that Sleeping TIGERS can improve sleep in anxious youth to a clinically significant degree.

Sex, Sleep Deprivation, and the Anxious Brain.

Insufficient sleep is a known trigger of anxiety. Nevertheless, not everyone experiences these effects to the same extent. One determining factor is sex, wherein women experience a greater anxiogenic impact in response to sleep loss than men. However, the underlying brain mechanism(s) governing this sleep-loss-induced anxiety increase, including the markedly different reaction in women and men, is unclear. Here, we tested the hypothesis that structural brain morphology in a discrete network of emotion-relevant regions represents one such explanatory factor. Healthy participants were assessed across sleep-rested and sleep-deprived conditions, with brain structure quantified using gray matter volume measures. Sleep loss triggered greater levels of anxiety in women compared with men. Reduced gray matter volume in the anterior insula and lateral orbitofrontal cortex predicted the anxiogenic impact of sleep loss in women, yet predicted resilience in men, and did so with high discrimination accuracy. In contrast, gray matter volume in ventromedial prefrontal cortex predicted the anxiogenic impact of sleep loss in both men and women. Structural human brain morphology therefore appears to represent one mechanistic pathway (and possible biomarker) determining anxiety vulnerability to sleep loss-a discovery that may help explain the higher prevalence of sleep disruption and anxiety in women.

Proinflammatory Cytokines, Mood, and Sleep in Interepisode Bipolar Disorder and Insomnia: A Pilot Study With Implications for Psychosocial Interventions.

OBJECTIVE: Proinflammatory cytokines are associated with bipolar disorder (BD), but less is known about how cytokines function during the interepisode period. This study examined cytokines, mood symptoms, and sleep in individuals with interepisode BD with complaints of insomnia. We also investigated the effects of a BD-specific modification of cognitive behavior therapy for insomnia (CBTI-BP) on cytokine levels. METHODS: Twenty-two adults with interepisode BD type I and insomnia were drawn from a subset of a National Institute of Mental Health funded study. Participants were randomly allocated to CBTI-BP (n = 11) or psychoeducation (n = 11). Participants completed a sleep diary, rated self-report measures of mania and depression, and provided samples assayed for interleukin (IL)-6 and tumor necrosis factor soluble receptor 2 (sTNF-R2). RESULTS: IL-6 was associated with mania symptoms (rs = 0.44, p = .041) and total sleep time (rs = -0.49, p = .026). IL-6 was related to depression symptoms at the trend level (rs = 0.43, p = .052). sTNF-R2 was not significantly related to mood or sleep measures. From pretreatment to posttreatment, CBTI-BP compared with psychoeducation was associated with a nonsignificant, large effect size decrease in IL-6 (z = -1.61, p = .13, d = -0.78) and a nonsignificant, small-medium effect size decrease in sTNF-R2 (z = -0.79, p = .44, d = -0.38). CONCLUSIONS: These findings provide preliminary evidence that IL-6 is related to mania symptoms and shorter total sleep time in interepisode BD. A treatment that targets sleep in BD could potentially decrease IL-6 although replication is warranted.

Vigilant attention to threat, sleep patterns, and anxiety in peripubertal youth.

BACKGROUND: Vigilant attention to threat is commonly observed in anxiety, undergoes developmental changes in early adolescence, and has been proposed to interfere with sleep initiation and maintenance. We present one of the first studies to use objective measures to examine associations between vigilant attention to threat and difficulties initiating and maintaining sleep in an early adolescent anxious sample. We also explore the moderating role of development (age, puberty) and sex. METHODS: Participants were 66 peripubertal youth (ages 9-14) with a primary anxiety disorder and 24 healthy control subjects. A dot-probe task was used to assess attentional bias to fearful relative to neutral face stimuli. Eye-tracking indexed selective attentional bias to threat, and reaction time bias indexed action readiness to threat. Sleep was assessed via actigraphy (e.g. sleep onset delay, wake after sleep onset, etc.), parent report (Children's Sleep Habits Questionnaire), and child report (Sleep Self-Report). The Pediatric Anxiety Rating Scale assessed anxiety severity. RESULTS: Eye-tracking initial threat fixation bias (ß = .33, p = .001) and threat dwell time bias (ß = .22, p = .041) were positively associated with sleep onset latency. Reaction time bias was positively associated with wake after sleep onset (ß = .24, p = .026) and parent-reported sleep disturbance (ß = .25, p = .019). Anxiety (severity, diagnosis) was not associated with these outcomes. Sex (ß = -.32, p = .036) moderated the relation between initial threat fixation bias and sleep onset latency, with a positive association for males (p = .005), but not for females (p = .289). Age and pubertal status did not moderate effects. CONCLUSIONS: Vigilant attention to threat is related to longer sleep onset and reduced sleep maintenance. These associations are not stronger in early adolescents with anxiety. Implications for early intervention or prevention that targets vigilant attention to threat to impact sleep disturbance, and vice versa, are discussed.