Treatment effect heterogeneity of cognitive behavioral therapy for insomnia - A meta-analysis.

Investigation of the heterogeneity of the treatment effect (HTE) might guide the optimization of cognitive behavioral therapy for insomnia (CBT-I). This study examined HTE in CBT-I thereby analyzing if treatment setting, control group, different CBT-I components, and patient characteristics drive HTE. Randomized controlled trials investigating CBT-I were included. Bayesian random effect meta-regressions were specified to examine variances between the intervention and control groups regarding post-treatment symptom severity. Subgroup analyses analyzing treatment setting and control groups and covariate analysis analyzing treatment components and patient characteristics were specified. No significant HTE in CBT-I was found for the overall data set, settings and control groups. The covariate analyses yielded significant results for baseline severity and the treatment component relaxation therapy. Thus, this study identified potential causes for HTE in CBT-I for the first time, showing that it might be worthwhile to further examine possibilities for precision medicine in CBT-I.

Chronic insomnia, REM sleep instability and emotional dysregulation: A pathway to anxiety and depression?

The world-wide prevalence of insomnia disorder reaches up to 10% of the adult population. Women are more often afflicted than men, and insomnia disorder is a risk factor for somatic and mental illness, especially depression and anxiety disorders. Persistent hyperarousals at the cognitive, emotional, cortical and/or physiological levels are central to most theories regarding the pathophysiology of insomnia. Of the defining features of insomnia disorder, the discrepancy between minor objective polysomnographic alterations of sleep continuity and substantive subjective impairment in insomnia disorder remains enigmatic. Microstructural alterations, especially in rapid eye movement sleep ("rapid eye movement sleep instability"), might explain this mismatch between subjective and objective findings. As rapid eye movement sleep represents the most highly aroused brain state during sleep, it might be particularly prone to fragmentation in individuals with persistent hyperarousal. In consequence, mentation during rapid eye movement sleep may be toned more as conscious-like wake experience, reflecting pre-sleep concerns. It is suggested that this instability of rapid eye movement sleep is involved in the mismatch between subjective and objective measures of sleep in insomnia disorder. Furthermore, as rapid eye movement sleep has been linked in previous works to emotional processing, rapid eye movement sleep instability could play a central role in the close association between insomnia and depressive and anxiety disorders.

An online behavioral self-help intervention rapidly improves acute insomnia severity and subjective mood during the coronavirus disease-2019 pandemic: a stratified randomized controlled trial.

STUDY OBJECTIVES: Stressful life events, such as the coronavirus disease-2019 (COVID-19) pandemic, can cause acute insomnia. Cognitive behavioral therapy for acute insomnia is effective but is both time and resource-intensive. This study investigated if an online behavioral self-help intervention, which has been successfully used alongside sleep restriction for acute insomnia, reduced insomnia severity and improved mood in acute insomnia. This study also assessed good sleepers to explore if a "sleep vaccination" approach was feasible. METHODS: In this online stratified randomized controlled trial, 344 participants (103 good sleepers and 241 participants with DSM-5 acute insomnia) were randomized to receive the intervention/no intervention (good sleepers) or intervention/intervention after 28 days (poor sleepers). Insomnia severity was assessed using the ISI (primary outcome), and anxiety and depression using the GAD-7/PHQ-9 (secondary outcomes) at baseline, 1 week, 1 month, and 3-month follow-up. RESULTS: In people with acute insomnia, relative to baseline, there were significant reductions in ISI (dz = 1.17), GAD-7 (dz = 0.70), and PHQ-9 (dz = 0.60) scores at 1-week follow-up. ISI, GAD-7, and PHQ-9 scores were significantly lower at all follow-up time points, relative to baseline. Subjective diary-derived sleep continuity was unaffected. No beneficial effects on sleep or mood were observed in good sleepers. CONCLUSIONS: An online behavioral self-help intervention rapidly reduces acute insomnia severity (within 1 week), and benefits mood in people with acute insomnia. These beneficial effects are maintained up to 3 months later. Although the use of the intervention is feasible in good sleepers, their subjective sleep was unaffected. CLINICAL TRIAL REGISTRATION: Testing an early online intervention for the treatment of disturbed sleep during the COVID-19 pandemic; prospectively registered at ISRCTN on 8 April 2020 (identifier: ISRCTN43900695).

Digital cognitive behavioural therapy for insomnia reduces insomnia in nurses suffering from shift work disorder: A randomised-controlled pilot trial.

Insomnia is a primary symptom of shift work disorder, yet it remains undertreated. This randomised-controlled pilot trial examined the efficacy of a digital, guided cognitive behavioural therapy for insomnia adapted to shift work (SleepCare) in nurses with shift work disorder. The hypothesis was that SleepCare reduces insomnia severity compared with a waitlist control condition. A total of 46 unmedicated nurses suffering from shift work disorder with insomnia (age: 39.7 ± 12.1 years; 80.4% female) were randomised to the SleepCare group or the waitlist control group. The primary outcome measure was the Insomnia Severity Index. Other questionnaires on sleep, mental health and occupational functioning, sleep diary data and actigraphy data were analysed as secondary outcomes. Assessments were conducted before (T0), after the intervention/waitlist period (T1), and 6 months after treatment completion (T2). The SleepCare group showed a significant reduction in insomnia severity from T0 to T1 compared with the control condition (ß = -4.73, SE = 1.12, p < 0.001). Significant improvements were observed in sleepiness, dysfunctional beliefs about sleep, pre-sleep arousal, sleep effort, self-reported sleep efficiency and sleep onset latency. No significant effect was found in actigraphy data. Depressive and anxiety symptoms, cognitive irritation and work ability improved significantly. Overall, satisfaction and engagement with the intervention was high. SleepCare improved insomnia severity, sleep, mental health and occupational functioning. This is the first randomised-controlled trial investigating the efficacy of digital cognitive behavioural therapy for insomnia in a population suffering from shift work disorder with insomnia. Future research should further explore these effects with larger sample sizes and active control conditions.

Genome-wide association analysis of composite sleep health scores in 413,904 individuals.

Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, and together may provide a more complete picture of sleep health, while also illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p<8.3e-9), along with 341 previously reported loci (p<5e-08). The heritability of the first three SHS-PCs equals or exceeds that of SHS-ADD (SNP-h2=0.094), while revealing sleep-domain-specific genetic discoveries. Significant loci enrich in multiple brain tissues and in metabolic and neuronal pathways. Post GWAS analyses uncover novel genetic mechanisms underlying sleep health and reveal connections to behavioral, psychological, and cardiometabolic traits.

Towards the neurobiology of insomnia: A systematic review of neuroimaging studies.

Insomnia disorder signifies a major public health concern. The development of neuroimaging techniques has permitted to investigate brain mechanisms at a structural and functional level. The present systematic review aims at shedding light on functional, structural, and metabolic substrates of insomnia disorder by integrating the available published neuroimaging data. The databases PubMed, PsycARTICLES, PsycINFO, CINAHL and Web of Science were searched for case-control studies comparing neuroimaging data from insomnia patients and healthy controls. 85 articles were judged as eligible. For every observed finding of each study, the effect size was calculated from standardised mean differences, statistic parameters and figures, showing a marked heterogeneity that precluded a comprehensive quantitative analysis. From a qualitative point of view, considering the findings of significant group differences in the reported regions across the articles, this review highlights the major involvement of the anterior cingulate cortex, thalamus, insula, precuneus and middle frontal gyrus, thus supporting some central themes in the debate on the neurobiology of and offering interesting insights into the psychophysiology of sleep in this disorder.

Causal Association Between Subtypes of Excessive Daytime Sleepiness and Risk of Cardiovascular Diseases.

BACKGROUND: Excessive daytime sleepiness (EDS), experienced in 10% to 20% of the population, has been associated with cardiovascular disease and death. However, the condition is heterogeneous and is prevalent in individuals having short and long sleep duration. We sought to clarify the relationship between sleep duration subtypes of EDS with cardiovascular outcomes, accounting for these subtypes. METHODS AND RESULTS: We defined 3 sleep duration subtypes of excessive daytime sleepiness: normal (6-9 hours), short (<6 hours), and long (>9 hours), and compared these with a nonsleepy, normal-sleep-duration reference group. We analyzed their associations with incident myocardial infarction (MI) and stroke using medical records of 355 901 UK Biobank participants and performed 2-sample Mendelian randomization for each outcome. Compared with healthy sleep, long-sleep EDS was associated with an 83% increased rate of MI (hazard ratio, 1.83 [95% CI, 1.21-2.77]) during 8.2-year median follow-up, adjusting for multiple health and sociodemographic factors. Mendelian randomization analysis provided supporting evidence of a causal role for a genetic long-sleep EDS subtype in MI (inverse-variance weighted ß=1.995, P=0.001). In contrast, we did not find evidence that other subtypes of EDS were associated with incident MI or any associations with stroke (P>0.05). CONCLUSIONS: Our study suggests the previous evidence linking EDS with increased cardiovascular disease risk may be primarily driven by the effect of its long-sleep subtype on higher risk of MI. Underlying mechanisms remain to be investigated but may involve sleep irregularity and circadian disruption, suggesting a need for novel interventions in this population.

The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023.

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).

The importance and limitations of polysomnography in insomnia disorder-a critical appraisal.

The importance polysomnography (PSG) in the diagnosis and treatment process of insomnia disorder (ID) remains highly disputed. This review summarises the state of the science regarding PSG indications and findings in ID, and the indications to conduct PSG in ID as stated by relevant guidelines. It then highlights the most relevant questions regarding the topic, including the relevance of ID subtyping, to allow an individualised pharmacological or psychotherapeutic treatment approach.

World sleep society international sleep medicine guidelines position statement endorsement of "behavioral and psychological treatments for chronic insomnia disorder in adults: An American Academy of sleep medicine clinical practice guidelines".

This paper summarizes the position statement of the World Sleep Society (WSS) International Guidelines Committee regarding the Clinical Practice Guidelines on the Behavioral and Psychological Treatments for Chronic Insomnia Disorder in Adults prepared by a task force of the American Academy of Sleep Medicine (AASM). The practice guidelines were reviewed for their relevance and applicability to the practice of sleep medicine around the world. The WSS Work Group endorsed the AASM strong recommendation for Multicomponent Cognitive Behavioral Therapy as the treatment of choice for Insomnia Disorder and conditional endorsement for its single-therapy components (sleep restriction, stimulus control, relaxation); use of sleep hygiene education as single therapy was not endorsed due to lack of evidence for its efficacy. The strong recommendation for multicomponent CBT-I applied to patients with chronic insomnia disorder with or without comorbid psychiatric and medical conditions. Main caveats with regard to CBT-I remains the lack of adequately trained therapists and variability in terms of training available in different parts of the world. Unanswered questions about the applicability, availability, accessibility and potential sociodemographic (age, sex, ethnicity, regions) moderators of treatment outcomes were discussed. Despite growing evidence documenting the benefits of digital CBT-I, individual, in-person CBT-I delivered by a trained professional (mental health) provider is regarded as the optimal method to deliver CBT-I.

Associations between sleep health and grey matter volume in the UK Biobank cohort (n = 33 356).

As suggested by previous research, sleep health is assumed to be a key determinant of future morbidity and mortality. In line with this, recent studies have found that poor sleep is associated with impaired cognitive function. However, to date, little is known about brain structural abnormalities underlying this association. Although recent findings link sleep health deficits to specific alterations in grey matter volume, evidence remains inconsistent and reliant on small sample sizes. Addressing this problem, the current preregistered study investigated associations between sleep health and grey matter volume (139 imaging-derived phenotypes) in the UK Biobank cohort (33 356 participants). Drawing on a large sample size and consistent data acquisition, sleep duration, insomnia symptoms, daytime sleepiness, chronotype, sleep medication and sleep apnoea were examined. Our main analyses revealed that long sleep duration was systematically associated with larger grey matter volume of basal ganglia substructures. Insomnia symptoms, sleep medication and sleep apnoea were not associated with any of the 139 imaging-derived phenotypes. Short sleep duration, daytime sleepiness as well as late and early chronotype were associated with solitary imaging-derived phenotypes (no recognizable pattern, small effect sizes). To our knowledge, this is the largest study to test associations between sleep health and grey matter volume. Clinical implications of the association between long sleep duration and larger grey matter volume of basal ganglia are discussed. Insomnia symptoms as operationalized in the UK Biobank do not translate into grey matter volume findings.

Adherence to sleep restriction therapy - An evaluation of existing measures.

Sleep restriction, a key element of cognitive behavioural therapy for insomnia, involves considerable behavioural changes in patients' lives, leading to side-effects like increased daytime sleepiness. Studies on sleep restriction rarely report adherence, and when assessed it is often limited to the average number of therapy sessions attended. This study aims to systematically evaluate different measures of adherence to cognitive behavioural therapy for insomnia and their relationship with treatment outcome. This is a secondary analysis of data from a randomized controlled trial investigating cognitive behavioural therapy for insomnia (Johann et al. (2020) Journal of Sleep Research, 29, e13102). The sample included 23 patients diagnosed with insomnia according to DSM-5 criteria who underwent 8 weeks of cognitive behavioural therapy for insomnia. The following adherence measures based on sleep diary data were used: number of sessions completed; deviations from agreed time in bed; average percentage of patients deviating from bedtime by 15, 30 or 60 min; variability of bedtime and wake-up time; change in time in bed from pre- to post-assessment. Treatment outcome was assessed using the Insomnia Severity Index. Multiple regression models were employed, and insomnia severity was controlled for. Results showed that none of the adherence measures predict insomnia severity. Baseline insomnia severity, dysfunctional thoughts and attitudes about sleep, depression or perfectionism did not predict adherence. The limited variance in the outcome parameter due to most patients benefiting from treatment and the small sample size may explain these findings. Additionally, using objective measures like actigraphy could provide a better understanding of adherence behaviour. Lastly, the presence of perfectionism in patients with insomnia may have mitigated adherence problems in this study.

Convergent abnormality in the subgenual anterior cingulate cortex in insomnia disorder: A revisited neuroimaging meta-analysis of 39 studies.

The neurobiological underpinnings of insomnia disorder (ID) are still poorly understood. A previous meta-analysis conducted by our research group in 2018 revealed no consistent regional alterations based on the limited number of eligible studies. Given the number of studies published during the last few years, we revisited the meta-analysis to provide an update to the field. Following the best-practice guidelines for conducting neuroimaging meta-analyses, we searched several databases (PubMed, Web of Science, and BrainMap) and identified 39 eligible structural and functional studies, reporting coordinates reflecting significant group differences between ID patients and healthy controls. A significant convergent regional alteration in the subgenual anterior cingulate cortex (sgACC) was observed using the activation likelihood estimation algorithm. Behavioural decoding using the BrainMap database indicated that this region is involved in fear-related emotional and cognitive processing. The sgACC showed robust task-based co-activation in meta-analytic connectivity modelling and task-free functional connectivity in a resting-state functional connectivity analysis with the main hubs of the salience and default mode networks, including the posterior cingulate cortex and dorsal ACC, amygdala, hippocampus, and medial prefrontal cortex. Collectively, the findings from this large-scale meta-analysis suggest a critical role of the sgACC in the pathophysiology of ID.

Discriminating Paradoxical and Psychophysiological Insomnia Based on Structural and Functional Brain Images: A Preliminary Machine Learning Study.

Insomnia disorder (ID) is a prevalent mental illness. Several behavioral and neuroimaging studies suggested that ID is a heterogenous condition with various subtypes. However, neurobiological alterations in different subtypes of ID are poorly understood. We aimed to assess whether unimodal and multimodal whole-brain neuroimaging measurements can discriminate two commonly described ID subtypes (i.e., paradoxical and psychophysiological insomnia) from each other and healthy subjects. We obtained T1-weighted images and resting-state fMRI from 34 patients with ID and 48 healthy controls. The outcome measures were grey matter volume, cortical thickness, amplitude of low-frequency fluctuation, degree centrality, and regional homogeneity. Subsequently, we applied support vector machines to classify subjects via unimodal and multimodal measures. The results of the multimodal classification were superior to those of unimodal approaches, i.e., we achieved 81% accuracy in separating psychophysiological vs. control, 87% for paradoxical vs. control, and 89% for paradoxical vs. psychophysiological insomnia. This preliminary study provides evidence that structural and functional brain data can help to distinguish two common subtypes of ID from each other and healthy subjects. These initial findings may stimulate further research to identify the underlying mechanism of each subtype and develop personalized treatments for ID in the future.

Sleep health dimensions and shift work as longitudinal predictors of cognitive performance in the UK Biobank cohort.

STUDY OBJECTIVES: The long-term effects of sleep health and shift work on cognitive performance are unclear. In addition, research has been limited by small sample sizes and short follow-up periods. We conducted one of the largest examinations of the longitudinal influence of sleep health dimensions and shift work on cognitive performance in people of middle and old age using data from the UK Biobank. The hypothesis was that poor sleep health and shift work would predict lower cognitive performance. METHODS: Self-reported sleep duration, daytime sleepiness, insomnia symptoms, chronotype, and shift work status were assessed as predictors at baseline. Cognitive performance was operationalized by a touchscreen test battery at follow-up between 7.4 ±â€…2.2 and 9.0 ±â€…0.9 years after baseline assessment, depending on the specific task. Models were performed for each cognitive domain including relevant confounders (e.g. depression). The alpha level was set at p < 0.01 for all analyzes. RESULTS: The study sample comprised 9394 participants for the reasoning task, 30 072 for the reaction time task, 30 236 for the visual memory task, 2019 for the numeric memory task, and 9476 for the prospective memory task. Shift work without night shifts (ß = -2.0 × 10-1 ± 6.5 × 10-2, p = 0.002) and with night shifts (ß = -1.9 × 10-1 ± 7.2 × 10-2, p = 0.010) predicted a significantly reduced performance in the reasoning task. Short sleep duration (ß = -2.4 × 10-1 ± 7.9 × 10-2, p = 0.003) and shift work without night shifts (ß = -3.9 × 10-1 ± 1.2 × 10-1, p = 0.002) predicted a significantly lower performance in the task probing prospective memory. CONCLUSIONS: Our results suggest that, after controlling for confounding variables, shift work, and short sleep duration are important predictors for cognitive performance in people of middle and old age. Further work is required to examine causal mechanisms of the observed associations.

The Effects of Cognitive Behavioral Therapy for Insomnia on Multidimensional Perfectionism.

Perfectionism is related to insomnia and objective markers of disturbed sleep. This study examined whether multidimensional perfectionism is related to dysfunctional beliefs about sleep, sleep-effort, pre-sleep arousal, and polysomnography-determined markers of sleep among individuals with insomnia. The effects of cognitive behavioral therapy for insomnia (CBT-I) on perfectionism was also examined. This was a secondary analysis of a randomized controlled trial on CBT-I. Forty-three insomnia patients were randomized to treatment (receiving CBT-I) or waitlist control groups. Sleep was recorded using polysomnography at baseline. Participants completed measures of perfectionism, dysfunctional beliefs about sleep, sleep-effort and pre-sleep arousal at baseline and posttreatment. Total perfectionism scores and doubts about action, concern over mistakes and personal standards were each significantly related to increased sleep effort, pre-sleep arousal and dysfunctional beliefs about sleep at baseline. Patients receiving treatment displayed increased total perfectionism scores posttreatment d = .49. In those receiving treatment, levels of organization d = .49 and parental expectations d = .47 were significantly increased posttreatment, relative to baseline. In line with the literature, our results confirm that perfectionism is related to insomnia. Here, insomnia was related to increased sleep effort, pre-sleep arousal and dysfunctional beliefs about sleep. The propensity to maintain a high standard of order and organization may be elevated following CBT-I, considering the treatment protocol expects patients to strictly adhere to a set of clearly defined rules. Levels of parental expectations may be increased following CBT-I since the patient-therapist-relationship may trigger implicit expectations in patients which are reminiscent of their relationship to their parents.

The potential of biomarkers for diagnosing insomnia: Consensus statement of the WFSBP Task Force on Sleep Disorders.

OBJECTIVES: Thus far, the diagnosis of insomnia is based on purely clinical criteria. Although a broad range of altered physiological parameters has been identified in insomniacs, the evidence to establish their diagnostic usefulness is very limited. Purpose of this WFSBP Task Force consensus paper is to systematically evaluate a series of biomarkers as potential diagnostic tools for insomnia. METHODS: A newly created grading system was used for assessing the validity of various measurements in establishing the diagnosis of insomnia; these measurements originated from relevant studies selected and reviewed by experts. RESULTS: The measurements with the highest diagnostic performance were those derived from psychometric instruments. Biological measurements which emerged as potentially useful diagnostic instruments were polysomnography-derived cyclic alternating pattern, actigraphy, and BDNF levels, followed by heart rate around sleep onset, deficient melatonin rhythm, and certain neuroimaging patterns (mainly for the activity of frontal and pre-frontal cortex, hippocampus and basal ganglia); yet, these findings need replication, as well as establishment of commonly accepted methodology and diagnostic cut-off points. Routine polysomnography, EEG spectral analysis, heart rate variability, skin conductance, thermoregulation, oxygen consumption, HPA axis, and inflammation indices were not shown to be of satisfactory diagnostic value. CONCLUSIONS: Apart from psychometric instruments which are confirmed to be the gold standard in diagnosing insomnia, six biomarkers emerge as being potentially useful for this purpose.