Sleep to Reduce Incident Depression Effectively (STRIDE): study protocol for a randomized controlled trial comparing stepped-care cognitive-behavioral therapy for insomnia versus sleep education control to prevent major depression

BACKGROUND: Prevention of major depressive disorder (MDD) is a public health priority. Strategies targeting individuals at elevated risk for MDD may guide effective preventive care. Insomnia is a reliable precursor to depression, preceding half of all incident and relapse cases. Thus, insomnia may serve as a useful entry point for preventing MDD. Cognitive-behavioral therapy for insomnia (CBT-I) is recommended as the first-line treatment for insomnia, but widespread implementation is limited by a shortage of trained specialists. Innovative stepped-care approaches rooted in primary care can increase access to CBT-I and reduce rates of MDD. METHODS/DESIGN: We propose a large-scale stepped-care clinical trial in the primary care setting that utilizes a sequential, multiple assignment, randomized trial (SMART) design to determine the effectiveness of dCBT-I alone and in combination with clinician-led CBT-I for insomnia and the prevention of MDD incidence and relapse. Specifically, our care model uses digital CBT-I (dCBT-I) as a first-line intervention to increase care access and reduce the need for specialist resources. Our proposal also adds clinician-led CBT-I for patients who do not remit with first-line intervention and need a more personalized approach from specialty care. We will evaluate negative repetitive thinking as a potential treatment mechanism by which dCBT-I and CBT-I benefit insomnia and depression outcomes. DISCUSSION: This project will test a highly scalable model of sleep care in a large primary care system to determine the potential for wide dissemination and implementation to address the high volume of population need for safe and effective insomnia treatment and associated prevention of depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT03322774. Registered on October 26, 2017

Objective sleep disturbance is associated with poor response to cognitive and behavioral treatments for insomnia in postmenopausal women

STUDY OBJECTIVES: To determine whether insomnia patients with objective sleep disturbance are less responsive to cognitive and behavioral treatments than those without objective sleep disturbance, characterize effects of insomnia therapy on objective sleep, and determine whether reductions in nocturnal cognitive arousal correspond to changes in objective sleep. METHODS: Secondary analysis of a single-site, randomized controlled trial. 113 postmenopausal women (56.40 ± 5.34 years) with menopause-related insomnia disorder were randomized to three treatment conditions: cognitive-behavioral therapy for insomnia (CBTI), sleep restriction therapy (SRT), or sleep education control. Primary outcomes were the Insomnia Severity Index (ISI) and polysomnography (PSG) sleep parameters and were collected at pretreatment, posttreatment, and six-month follow-up. RESULTS: Patients with lower pretreatment PSG sleep efficiency had lower rates of insomnia remission after active treatment relative to those with higher sleep efficiency (37.8% vs 61.8%). Neither CBTI and SRT produced clinically meaningful effects on PSG sleep. Exploratory analyses revealed that reductions in nocturnal cognitive arousal were associated with decreases in PSG sleep latency, but not wake after sleep onset. CONCLUSIONS: Our findings support an emerging literature suggesting that insomnia patients with objective sleep disturbance may have blunted response to insomnia therapy. Research is needed to enhance treatments to better improve insomnia in patients with objective sleep disturbance. A lack of observed CBTI and SRT effects on PSG sleep suggests that these therapies may be presently ill-designed to improve objective sleep. Nocturnal cognitive arousal may represent an entry point to improve objective sleep latency in insomnia. NAME: Behavioral Treatment of Menopausal Insomnia: Sleep and Daytime Outcomes. URL: clinicaltrials.gov. Registration: NCT01933295

Improved resilience following digital cognitive behavioral therapy for insomnia protects against insomnia and depression one year later

BACKGROUND: While the negative consequences of insomnia are well-documented, a strengths-based understanding of how sleep can increase health promotion is still emerging and much-needed. Correlational evidence has connected sleep and insomnia to resilience; however, this relationship has not yet been experimentally tested. This study examined resilience as a mediator of treatment outcomes in a randomized clinical trial with insomnia patients. METHODS: Participants were randomized to either digital cognitive behavioral therapy for insomnia (dCBT-I; n = 358) or sleep education control (n = 300), and assessed at pre-treatment, post-treatment, and 1-year follow-up. A structural equation modeling framework was utilized to test resilience as a mediator of insomnia and depression. Risk for insomnia and depression was also tested in the model, operationalized as a latent factor with sleep reactivity, stress, and rumination as indicators (aligned with the 3-P model). Sensitivity analyses tested the impact of change in resilience on the insomnia relapse and incident depression at 1-year follow-up. RESULTS: dCBT-I resulted in greater improvements in resilience compared to the sleep education control. Furthermore, improved resilience following dCBT-I lowered latent risk, which was further associated with reduced insomnia and depression at 1-year follow-up. Sensitivity analyses indicated that each point improvement in resilience following treatment reduced the odds of insomnia relapse and incident depression 1 year later by 76% and 65%, respectively. CONCLUSIONS: Improved resilience is likely a contributing mechanism to treatment gains following insomnia therapy, which may then reduce longer-term risk for insomnia relapse and depression

Predicting circadian misalignment with wearable technology: Validation of wrist-worn actigraphy and photometry in night shift workers

STUDY OBJECTIVES: A critical barrier to successful treatment of circadian misalignment in shift workers is determining circadian phase in a clinical or field setting. Light and movement data collected passively from wrist actigraphy can generate predictions of circadian phase via mathematical models; however, these models have largely been tested in non-shift working adults. This study tested the feasibility and accuracy of actigraphy in predicting dim light melatonin onset (DLMO) in fixed-night shift workers. METHODS: A sample of 45 night shift workers wore wrist actigraphs before completing DLMO in the laboratory (17.0 days ± 10.3 SD). DLMO was assessed via 24 hourly saliva samples in dim light (&10 lux). Data from actigraphy were provided as input to a mathematical model to generate predictions of circadian phase. Agreement was assessed and compared to average sleep timing on non-workdays as a proxy of DLMO. Model code and a prototype assessment tool are available open source. RESULTS: Model predictions of DLMO showed good concordance with in-lab DLMO, with a Lin\u27s concordance coefficient of 0.70, which was twice as high as agreement using average sleep timing as a proxy of DLMO. The absolute mean error of the predictions was 2.88 hours, with 76% and 91% of the predictions falling with 2 and 4 hours, respectively. CONCLUSION: This study is the first to demonstrate the use of wrist actigraphy-based estimates of circadian phase as a clinically useful and valid alternative to in-lab measurement of DLMO in fixed night shift workers. Future research should explore how additional predictors may impact accuracy

Mother-to-Infant Bonding is Associated with Maternal Insomnia, Snoring, Cognitive Arousal, and Infant Sleep Problems and Colic

Objective: Emerging evidence links maternal and infant sleep problems to impairments in the mother-to-infant bond, but the independence and directionality of these associations remain unclear. The present study characterized concurrent and prospective effects of maternal sleep disturbances and poor infant sleep on the mother-infant relationship. As common sequalae of problematic sleep, nocturnal cognitive hyperarousal and daytime sleepiness were investigated as facilitating mechanisms. Participants: Sixty-seven pregnant women enrolled in a prospective study on maternal sleep. Methods: Sociodemographic information and clinical symptoms were measured prenatally then weekly across the first two postpartum months. Women reported insomnia symptoms, sleep duration, snoring, daytime sleepiness, nocturnal cognitive arousal (broadly focused and perinatal-specific), perseverative thinking, depression, infant colic, infant sleep quality, and mother-infant relationship quality. Mixed effects models were conducted to test hypotheses. Results: Prenatal snoring and weak maternal-fetal attachment augured poorer postpartum bonding. Poor infant sleep was associated with increased odds for maternal insomnia and short sleep. Impairments in the mother-to-infant bond were linked to maternal insomnia, nocturnal perinatal-focused rumination, daytime sleepiness, depression, and poor infant sleep. Postnatal insomnia predicted future decreases in mother-infant relationship quality, and nocturnal cognitive hyperarousal partially mediated this association. Conclusions: Both maternal and infant sleep problems were associated with poorer mother-to-infant bonding, independent of the effects of maternal depression and infant colic. Perseverative thinking at night, particularly on infant-related concerns, was linked to impaired bonding, rejection and anger, and infant-focused anxiety. Improving maternal and infant sleep, and reducing maternal cognitive arousal, may improve the maternal-to-infant bond

Racial discrimination as a mediator of racial disparities in insomnia disorder

STUDY OBJECTIVES: Racial and ethnic minorities are more likely to suffer from insomnia that is more severe; however, few studies have examined mechanisms by which racial disparities in severity of insomnia disorder may arise. One potential mechanism for disparities in insomnia severity is perceived discrimination. This study tested discrimination as a mediator in the relationship between race and insomnia. METHODS: Participants were recruited from communities in the Detroit metropolitan area and were diagnosed with insomnia disorder using the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition). The final sample included 1,458 individuals. Insomnia symptom severity was assessed via the Insomnia Severity Index and self-reported racial discrimination was evaluated using a single item. Racial discrimination was tested as a mediator in the relationship between race and insomnia symptom severity. Individuals were categroized as either White or a racial minority (i.e., non White individuals), with sensitivity analyses examining Black individuals and non-Black racial minority groups. RESULTS: Consistent with our hypothesis, racial discrimination was a significant mediator accounting for 57.3% of the relationship between race and insomnia symptom severity. Sensitivity analyses indicated that the indirect effect of racial discrimination was stronger in the non-Black racial minority group compared to Black individuals. CONCLUSIONS: These results provide support that racial discrimination is likely an important mechanism by which racial and ethnic sleep disparities exist. Implications for prevention, intervention, and treatment of insomnia in racial minorities to reduce health disparities are discussed

Cognitive-behavioral therapy for insomnia prevents and alleviates suicidal ideation: Insomnia remission is a suicidolytic mechanism

STUDY OBJECTIVES: Insomnia is associated with elevated levels of suicidal thoughts and behaviors. Emerging evidence suggests that cognitive behavioral therapy for insomnia (CBTI) may reduce suicidal ideation (SI). However, the role of digital therapeutics in both the alleviation and prevention of SI remains unclear, and treatment mechanisms facilitating SI reductions have not been clearly identified. METHOD: 658 adults with DSM-5 insomnia disorder enrolled into a single-site randomized controlled trial evaluating the efficacy of digital CBTI relative to attention control. Outcomes were measured at pretreatment, posttreatment, and 1-year follow-up. RESULTS: Before treatment, 126 patients endorsed SI (19.1% prevalence). Among those with baseline SI, CBTI patients reported lower SI rates at posttreatment (30.0% vs 54.5%, p=.005) and 1-year follow-up (29.6% vs 46.8%, p=.042) relative to control. PRODCLIN analysis estimated that half of suicidolytic effects of CBTI were mediated through insomnia remission. Among those without baseline SI, CBTI did not directly prevent new onset SI. However, insomnia remitters reported lower rates of new onset SI at posttreatment relative to non-remitters (1.5% vs 6.5%, p=.009). Mediation analysis supported a significant indirect effect wherein CBTI increased likelihood of insomnia remission, which was associated with SI prevention (αβ=-3.13=5, 95%CI=-5.28, -0.96). CONCLUSION: Digital CBTI reduces insomnia symptoms, which promotes SI alleviation and prevention. For non-suicidal patients, digital CBTI may serve as a highly accessible monotherapy for improving sleep, thereby reducing risk for SI. For suicidal patients, digital CBTI may be appropriately administered as an adjunct treatment to support mainline intervention more directly targeting suicidogenic thoughts