Insomnia Disorder Research Articles

The joint association of insomnia disorder and lifestyle on the risk of activity-limiting spinal pain: the HUNT Study

ObjectivesTo investigate whether the combination of multiple healthy lifestyle factors modify the well-established association between insomnia disorder and risk of activity-limiting spinal pain. MethodsWe conducted a prospective study of 10,228 individuals who participated in two surveys over ∼11 years and were free of chronic pain in the neck, upper back, and lower back at baseline. Adjusted risk ratios (RRs) were calculated for the risk of activity-limiting chronic spinal pain (i.e., pain that impairs daily activities at work or leisure time) at follow-up associated with the joint association of insomnia disorder and the combination of five lifestyle factors (body mass index, leisure time physical activity, alcohol consumption, diet, and smoking) at baseline. ResultsOur data indicate an additive interaction between insomnia disorder and lifestyle on risk of activity-limiting spinal pain, i.e., compared with participants without insomnia disorder and the best lifestyle score, participants with insomnia disorder and the worst lifestyle score had a RR of activity-limiting spinal pain of 3.57 (95 % CI: 2.65–4.80); participants with insomnia disorder and the best lifestyle score had a RR of 1.56 (95 % CI: 0.97–2.50); and those without insomnia disorder and the worst lifestyle score had a RR of 1.32 (95 % CI: 1.12–1.55). ConclusionsPoor lifestyle behaviour amplifies the adverse effect of insomnia disorder on the risk of activity-limiting chronic spinal pain.

Better characterizing sleep beliefs for personalized sleep health promotion: the French sleep beliefs scale validation study.

The Sleep Beliefs Scale (SBS) is a well-known tool to design and monitor personalized sleep health promotion at an individual and population level. The lack of an established French version limits the development of effective interventions targeting these populations. Thus, the aim of this study was to validate the French version of the SBS in a representative sample of the general population. Quota sampling was used to recruit 1,004 participants (18-65 years, mean age: 43 years, 54% of female) who underwent an online survey to complete the SBS, and to assess sleep schedules, sleep quality and disorders, and mental health. Cronbach's α coefficient, confirmatory factor analysis, item-internal consistency (IIC), and item discriminant validity (IDV) of the SBS were computed to assess internal validity while bivariate associations with sleep schedules, sleep quality and disorders, and mental health were used to assess external convergent and discriminant validity. The mean score on the SBS was 12.3 ± 4.9. Item 19 ("Quiet & Dark") showed the highest rate of correct answers (n = 801, 79.8%), while item 20 ("Recovering sleep") showed the lowest rate of correct answers (n = 246, 24.5%). Overall, the SBS showed satisfactory internal consistency (α = 0.87) and confirmed the three-factor structure proposed by the original study. All items were found consistent (IIC > 0.4) and discriminant (IIC > IDV) except for item 20 ("recovering lost sleep by sleeping for a long time"). Females, older participants, and subjects with short time-in-bed, poor sleep quality, insomnia, and circadian rhythm disorder had higher SBS scores while participants with depressive symptoms had lower SBS scores. We successfully translated and validated the French version of the SBS in a representative sample, making it a reliable instrument for researchers and clinicians to assess and target sleep beliefs. Correct answers vary from 25 to 80% which underlines the importance of continuing sleep health promotion campaigns by targeting poorly understood behaviors. Our findings also shed light on the fickleness of beliefs that are prone to vary within individuals across time, in step with societal changes. Several associated factors were identified, thus contributing to our understanding of sleep beliefs and offering insights for personalized approaches to enhance sleep health and overall well-being.

Factors influencing shared decision-making for insomnia and obstructive sleep apnea treatment among Veterans with mild traumatic brain injury.

We elicited perspectives of clinical stakeholders and Veterans regarding barriers and facilitators to implementing shared decision-making (SDM) for comorbid mild traumatic brain injury (mTBI) and sleep disorders in the Veterans Health Administration. We also compared the perspectives of clinical stakeholders and Veterans regarding determinants of SDM. Semistructured interviews were conducted with 29 clinical stakeholders and 20 Veterans (n = 49). Clinical stakeholders included Veterans Health Administration providers and policymakers involved in the management of mTBI and/or sleep disorders (insomnia disorder, obstructive sleep apnea). Veterans included those with a clinician-confirmed mTBI who received care for insomnia disorder and/or obstructive sleep apnea within the past year. Themes were identified using a descriptive and interpretive approach to qualitative analysis. We compared results across clinical stakeholders and Veterans. Barriers to implementing SDM were identified by both groups at the patient (eg, mTBI sequalae), provider (eg, deprioritization of Veteran preferences), encounter (eg, time constraints), and facility levels (eg, reduced care access). Similarly, both groups identified facilitators at the patient (eg, enhanced trust), provider (eg, effective communication), encounter (eg, decision support), and facility levels (eg, mitigating access barriers). Integrated services and provider discontinuity were factors identified by clinical stakeholders and Veterans alone, respectively. Our study revealed factors shaping the implementation of SDM at the levels of the patient, provider, encounter, and facility. Findings can inform the development of strategies aimed at implementing SDM for comorbid mTBI and sleep disorders, promoting patient-centered care and enhancing clinical outcomes. Kinney AR, Brenner LA, Nance M, etal. Factors influencing shared decision-making for insomnia and obstructive sleep apnea treatment among Veterans with mild traumatic brain injury. J Clin Sleep Med. 2024;20(5):801-812.

Deep transfer learning for automated single-lead EEG sleep staging with channel and population mismatches.

Introduction: Automated sleep staging using deep learning models typically requires training on hundreds of sleep recordings, and pre-training on public databases is therefore common practice. However, suboptimal sleep stage performance may occur from mismatches between source and target datasets, such as differences in population characteristics (e.g., an unrepresented sleep disorder) or sensors (e.g., alternative channel locations for wearable EEG). Methods: We investigated three strategies for training an automated single-channel EEG sleep stager: pre-training (i.e., training on the original source dataset), training-from-scratch (i.e., training on the new target dataset), and fine-tuning (i.e., training on the original source dataset, fine-tuning on the new target dataset). As source dataset, we used the F3-M2 channel of healthy subjects (N = 94). Performance of the different training strategies was evaluated using Cohen's Kappa (κ) in eight smaller target datasets consisting of healthy subjects (N = 60), patients with obstructive sleep apnea (OSA, N = 60), insomnia (N = 60), and REM sleep behavioral disorder (RBD, N = 22), combined with two EEG channels, F3-M2 and F3-F4. Results: No differences in performance between the training strategies was observed in the age-matched F3-M2 datasets, with an average performance across strategies of κ = .83 in healthy, κ = .77 in insomnia, and κ = .74 in OSA subjects. However, in the RBD set, where data availability was limited, fine-tuning was the preferred method (κ = .67), with an average increase in κ of .15 to pre-training and training-from-scratch. In the presence of channel mismatches, targeted training is required, either through training-from-scratch or fine-tuning, increasing performance with κ = .17 on average. Discussion: We found that, when channel and/or population mismatches cause suboptimal sleep staging performance, a fine-tuning approach can yield similar to superior performance compared to building a model from scratch, while requiring a smaller sample size. In contrast to insomnia and OSA, RBD data contains characteristics, either inherent to the pathology or age-related, which apparently demand targeted training.

Cognitive Behavioural Therapy for insomnia decreases the discrepancy between objective and subjective measures of sleep.

Individuals with insomnia disorder often exhibit differences between reported experiences of sleep and objectively measured sleep parameters; however, the implications of this subjective-objective sleep discrepancy during treatment remains unclear. The aim of this study was to investigate the impact of cognitive behavioural therapy for insomnia (CBT-I) on the discrepancy between objective and subjective measures of sleep, and to assess whether changes in clinical variables such as depression, anxiety, fatigue, and beliefs about sleep, were related to changes in discrepancy. Twenty-five participants with insomnia disorder were enrolled in group CBT-I. Sleep measures were continually sampled from baseline until 2 weeks post-treatment with both objective (i.e., actigraphy) and subjective (i.e., sleep diary) methods. The subjective-objective discrepancy significantly decreased from baseline early on in treatment (following the second session) and were maintained at post-treatment for sleep onset latency, wake after sleep onset (WASO) and sleep efficiency (SE). Total sleep time (TST) discrepancy and misperception decreased from baseline to post-treatment. Improvement in depression symptoms, fatigue symptoms, and negative beliefs about sleep were significantly correlated with the decrease in the discrepancy for WASO and SE. These findings suggest that CBT-I resolves the mismatch between objective and subjective sleep parameters early in treatment for adults with insomnia. Sleep misperception improved from underestimating to accurately estimating TST. Improvement of psychological symptoms were related to decrease in sleep discrepancies across treatment. Future research is needed to explore how feedback on objective and subjective sleep discrepancy may impact sleep perception across treatment with CBT-I.

Assessing insomnia after stroke: a diagnostic validation of the Sleep Condition Indicator in self-reported stroke survivors.

Insomnia is common after stroke and is associated with poorer recovery and greater risk of subsequent strokes. Yet, no insomnia measures have been validated in English-speaking individuals affected by stroke. This prospective diagnostic validation study investigated the discriminatory validity and optimal diagnostic cut-off of the Sleep Condition Indicator when screening for Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) insomnia disorder post-stroke. A convenience sample of 180 (60.0% women, mean age=49.61 ± 12.41 years) community-based, adult (≥18 years) self-reported stroke survivors completed an online questionnaire. Diagnosis of DSM-5 insomnia disorder was based on analysis of a detailed sleep history questionnaire. Statistical analyses explored discriminant validity, convergent validity, relationships with demographic and mood variables, and internal consistency. Receiver operating characteristic curves were plotted to assess diagnostic accuracy. Data from the sleep history questionnaire suggested that 75 participants (41.67%) met criteria for DSM-5 insomnia disorder, 33 (18.33%) exhibited symptoms of insomnia but did not meet diagnostic criteria, and 72 (40.0%) had no insomnia symptoms at the time of assessment. The Sleep Condition Indicator (SCI) demonstrated 'excellent' diagnostic accuracy in the detection of insomnia post-stroke, with an area under the curve of 0.86 (95% CI (0.81, 0.91)). The optimal cut-off was determined as being ≤13, yielding a sensitivity of 88.0% and a specificity of 71.43%. The findings of this study demonstrate the SCI to be a valid and reliable method with which to diagnose DSM-5 insomnia disorder and symptoms post-stroke. However, a lower threshold than is used in the general population may be necessary after stroke.

Analysis of the Improvement Sequence in Insomnia Symptoms and Factors Influencing the Treatment Outcomes of Smartphone-Delivered CBT in Patients with Insomnia Disorder.

The effectiveness of medication combined with smartphone-delivered cognitive behavioral therapy for insomnia (CBT-I) has been well verified, but there are few studies on the sequence of remission of insomnia symptoms. This study aims to understand the sequence of symptom improvement and the factors influencing the treatment effectiveness in patients with insomnia. Smartphone-delivered CBT, as a form of Online CBT, allows for training through mobile devices at any time and place. We utilized the Good Sleep 365 app to conduct a survey, involving 2820 patients who met the baseline inclusion criteria. These patients were assessed using a general demographic questionnaire and the Pittsburgh Sleep Quality Index (PSQI) to evaluate general demographic information and insomnia symptoms, and subsequently underwent CBT training using the Good Sleep 365 app. A total of 1179 patients completed follow-ups at 4 weeks, 8 weeks, 16 weeks, and 24 weeks. At 4 weeks and 8 weeks, the descending order of the reduction rates of PSQI components (excluding component 6: use of sleeping medication) was: sleep latency, subjective sleep quality, sleep efficiency, sleep disturbance, sleep maintenance, and daytime dysfunction. At 16 weeks and 24 weeks, the descending order was subjective sleep quality, sleep latency, sleep efficiency, daytime dysfunction, sleep maintenance, and sleep disturbance. There were significant differences in the reduction rates of PSQI components (excluding component 6: use of sleeping medication) both at the same follow-up times and at different follow-up times (all P<0.05). Multivariable logistic regression analysis showed that patients older than 30 years and those with a college degree or above had better treatment outcomes, whereas those with a disease duration of more than three years had worse outcomes. The sequence of symptom improvement in patients with insomnia changes over time, and age, educational level, and duration of disease are factors influencing treatment outcomes.

Volume of the Dentate Gyrus/CA4 Hippocampal subfield mediates the interplay between sleep quality and depressive symptoms

BackgroundEmerging evidence increasingly suggests that poor sleep quality is associated with depressive symptoms. The hippocampus might play a crucial role in the interplay between sleep disturbance and depressive symptomatology, e.g., hippocampal atrophy is typically seen in both insomnia disorder and depression. Thus, examining the role of hippocampal volume in the interplay between poor sleep quality and depressive symptoms in large healthy populations is vital. MethodsWe investigated the association between self-reported sleep quality, depressive symptoms, and hippocampal total and subfields’ volumes in 1603 healthy young adults from the Behavioral Brain Research Project. Mediation analysis explored the mediating role of hippocampal volumes between sleep quality and depressive symptoms. ResultsSelf-reported sleep quality and depressive symptoms were positively correlated. In addition, it negatively related to three hippocampal subfields but not total hippocampal volume. In particular, hippocampal subfield DG and CA4 volumes mediated the interrelationship between poor sleep quality and depressive symptoms. ConclusionsOur findings improved the current understanding of the relationship between sleep disturbance, depressive symptomatology, and hippocampal subfields in healthy populations. Considering the crucial role of DG in hippocampal neurogenesis, our results suggest that poor sleep quality may contribute to depression through a reduction of DG volume leading to impaired neurogenesis which is crucial for the regulation of mood.

Anxiolytic-like effects of the dual orexin receptor antagonist daridorexant in rats

Dual orexin receptor antagonists (DORAs) belong to a novel class of sleep medications that function by blocking the actions of wakefulness-promoting orexin neuropeptides in sleep-wake centers of the brain. Orexins also transmit signals to brain nuclei that regulate emotions and stress responses. The effects of DORAs on anxiety-like reactions requires further exploration. The hyperarousal theory of insomnia suggests an underlying overactivation of the body's stress response systems, and a considerable proportion of insomnia patients suffers from concurrent anxiety disorders. Hence, it is important for physicians to be certain that novel insomnia treatments do not exacerbate, but rather alleviate, patients' anxiety and psychological stress responses. Our aim was to test the effect of the new DORA daridorexant on diverse anxiety- and fear-evoked behavioral and physiological reactions in rats to gain first insight into the drug's potential in humans. Daridorexant, given orally at 10, 30 and 100 mg/kg 1 h before testing, resulted in a dose-dependent reduction of fear-potentiated acoustic startle (FPS) reactions, schedule-induced polydipsia (SIP) and social stress-induced hyperthermia and tachycardia (SIH/T). Furthermore, under non-stressful, basal conditions, daridorexant reduced the heart rate of spontaneously hypertensive rats, which are considered a model of endogenous, sympathetic hyperactivation that can occur in insomnia or anxiety disorders. Daridorexant had no effect on ultrasound-induced, panic-like, defensive behavior (UIDB). We conclude that daridorexant rather attenuated and did not intensify fear/stress responses in rats. It was effective in models that simulate endophenotypes that are specific for post-traumatic stress, obsessive-compulsive, and social anxiety disorder.

The Psychosomatic Health Status of Polish Psychiatric Nurses in Relation to Socio-Demographic Variables

Objective: The main aim of the study was to assess the psychosomatic health status of psychiatric nurses based on sociodemographic variables. Materials and Methods: The research was conducted at the Mazovian Provincial Hospital in Ząbki on a group of 101 individuals working in nursing positions. All participants gave voluntary and free consent to participate in the study. The study obtained approval from the bioethical committee. The health status of the respondents was assessed using a standardized, validated GHQ-28 questionnaire. The level of significance was set at p=0.05. Results: Social dysfunction among participants increased with age and length of employment at the current workplace (p &lt; 0.05). Significantly higher scores (p &lt; 0.05) in this area were observed in individuals in marital relationships and those with higher education. The intensity of anxiety and insomnia was significantly higher (p &lt; 0.05) in individuals in marital relationships, respondents with secondary education, and those with a total work experience exceeding 30 years and over 15 years in the current workplace. The intensity of depressive symptoms was associated with a lack of higher education among respondents. The factor with the greatest impact on somatic symptoms among surveyed nurses (p &lt; 0.05) was age over 50. Conclusions: There is a significant association between the intensity of somatic symptoms, anxiety, insomnia, and functional disorders and the age of participants. There is a significant association between the intensity of anxiety and insomnia symptoms, functional impairments, and the marital status of participants. There is a significant association between the intensity of depressive symptoms, anxiety, insomnia, and social dysfunction and the education level of participants.

A Cross-Sectional Survey on Psychological Health and Influencing Factors Among 2628 Asymptomatic and Mild COVID-19 Patients in Fangcang Shelter Hospital.

The Coronavirus disease 2019 (COVID-19) remains a global public health concern. Many people have been forced to change their lifestyles, which has led to psychological and sleep problem. This study aims to investigate the psychological health problems and factors among patients in the Fangcang Shelter Hospital (FSH) during the COVID-19 pandemic. A Cross-Sectional survey was conducted to investigate the sleep, anxiety, depression and stress disorders of 2628 asymptomatic and mild patients treated in FSH of Zhengzhou, Henan Province, from 30 October to 6 December 2022, by scanning a WeChat two-dimensional code. Sociodemographic data and influencing factors in FSH were collected, Insomnia Severity Index (ISI), 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Impact of Event Scale-Revised (IES-R) were administered. Descriptive statistics, t-tests or analysis of variance, Spearman or Pearson correlation analysis, and multivariate regression analysis were used to explore the relationships between different variables and their impact on psychological health indicators. The proportions of patients with insomnia, depressive disorder, anxiety, and stress disorders were 33.49%, 35.80%, 31.74%, and 43.57%, respectively. Spearman correlation analysis demonstrated that factors such as gender, higher education level, positive nucleic acid test results, longer illness duration, underlying diseases, and extended electronic device use were associated with elevated psychological distress scores. Notably, within FSH, extended exposure to light, a noisy environment, and sleep schedule management significantly impacted the prevalence of insomnia, depression, anxiety, and stress disorders (p<0.01). Multivariable binary logistic regression analysis identified higher education level, light exposure, noisy environment, sleep management, and electronic device usage as the primary risk factors for psychological distress. Patients in FSH face psychological distress influenced by sociodemographic factors, environment, and lifestyle, highlighting the need for integrated psychological support in healthcare, particularly in temporary medical facilities during crises.

Sleep disorders during pregnancy

Pregnancy is associated with a number of physiological changes in a woman's body, which in turn affect the quality and duration of sleep. According to research, insomnia and other sleep disorders are associated with a high risk of adverse pregnancy outcomes, as well as postpartum complications. Understanding the mechanisms of sleep disorders during pregnancy is necessary to form an integrated approach in the management of this group of patients. The appointment of medicinal and non-medicinal therapies, as well as general recommendations for lifestyle correction in order to treat sleep disorders, is focused on the safe and prolific effect of a particular drug on the mother and fetus. This review also examined the safety profile of commonly used groups of drugs for sleep disorders during pregnancy.

Study on Correlation between Hyperarousal and Serum Inflammatory Factors Expression in Patients with Chronic Insomnia Disorder

Study on Correlation between Hyperarousal and Serum Inflammatory Factors Expression in Patients with Chronic Insomnia Disorder

The effect of insomnia on mild cognitive impairment in patients with vascular risks: results of a three-year longitudinal study

To assess the dynamics of sleep parameters based on the analysis of three items of HDRS-17, designed to measure the severity of insomnia, during 36 months of follow-up and their relationship with indicators of the cognitive phenotype in patients with vascular risk factors. The longitudinal study included 51 patients (mean age 57.7±6.2 years, 19 (37.3%) men)) who met the inclusion criteria. All participants underwent a general clinical examination with assessment of vascular risks and neuropsychological testing using the Montreal Cognitive Assessment (MoCA) and HDRS-17 at baseline and after 36 months. During the study, patients received stable basic therapy to prevent modifiable vascular risk factors. Sleeping pills were taken sporadically when there were complaints of problems falling asleep. During the 36-month study, as vascular cognitive impairment progressed from 23.7±2.6 to 22.1±2.4 points on the MoCA scale (p=0.01), mainly due to decreased attention (p=0.01), executive functions (EF) (p=0.01), memory (p=0.02), speech (p=0.02), an increase in sleep disturbances was observed (item 4: 0.8±0.02 to 1.9±0.1 points, p=0.01; point 5: 0.6±0.02 to 1.7±0.1 points, p=0.01) and depression (7.5±0.5 to 13.7±3.0 points, p=0.01) in patients with vascular risks. A strong inverse correlation was revealed between the values of items 4, 5, 6 on the HDRS-17 and the average MoCA-total scores (r=-0.85; r=-0.87; r=-0.8 (p<0.05)), memory index (r=-0.8; r=-0.75; r=-0.81 (p<0.05)), attention index (r=-0.88; r=-0.86; r=-0.83 (p<0.05)), index of executive functions (r=-0.87; r=-0.85; r=-0.8 (p<0.05)), respectively. The progression of cognitive impairment is associated with worsening insomnia disorders and depression in patients with vascular risks.

Examining insomnia disorder and stress generation among individuals who have experienced involuntary job loss

ObjectiveDepressed individuals generate more stressful life events than non-depressed individuals. Like depressive symptoms, the symptoms of insomnia disorder may lead to impaired decision-making, daytime sleepiness, fatigue, and emotion dysregulation, yet the prospective relationship with insomnia disorder and stress generation has not previously been investigated. We hypothesized that insomnia disorder within the first three months of involuntary job loss would lead to an increased number of stressful life events three-months later. MethodsThis project employed a longitudinal design consisting of two timepoints occurring approximately 3 months apart. A sample 136 participants with complete data was sourced from the Assessing Daily Activity Patterns through Occupational Transitions study. Insomnia disorder was diagnosed using the Duke Structured Interview for Sleep Disorders, and the number of stressful life events was assessed using the Life Events and Difficulties Schedule. ResultsA cross-lagged panel analysis utilizing Poisson and logistic regression techniques indicated that insomnia disorder at study baseline predicted an increased number of all stressful life events at follow-up (RR = 1.36, p = .01); conversely, stressful life events at baseline did not predict insomnia disorder (OR = 0.98, p = .87). ConclusionThese results support a stress-generation hypothesis of insomnia disorder. Findings highlight insomnia disorder as a potential target for intervention in the prevention of additional stress exposure among recently unemployed individuals, who have been shown to be at increased risk for adverse health and health disparities.

Effect of Psychological and Medication Therapies for Insomnia on Daytime Functions

Daytime functional impairments are the primary reasons for patients with insomnia to seek treatment, yet little is known about what the optimal treatment is for improving daytime functions and how best to proceed with treatment for patients whose insomnia has not remitted. To compare the efficacy of behavioral therapy (BT) and zolpidem as initial therapies for improving daytime functions among patients with insomnia and evaluate the added value of a second treatment for patients whose insomnia has not remitted. In this sequential multiple-assignment randomized clinical trial conducted at institutions in Canada and the US, 211 adults with chronic insomnia disorder were enrolled between May 1, 2012, and December 31, 2015, and followed up for 12 months. Statistical analyses were performed on an intention-to-treat basis in April and October 2023. Participants were randomly assigned to either BT or zolpidem as first-stage therapy, and those whose insomnia had not remitted received a second-stage psychological therapy (BT or cognitive therapy) or medication therapy (zolpidem or trazodone). Study outcomes were daytime symptoms of insomnia, including mood disturbances, fatigue, functional impairments of insomnia, and scores on the 36-item Short-Form Health Survey (SF-36) physical and mental health components. Among 211 adults with insomnia (132 women [63%]; mean [SD] age, 45.6 [14.9] years), 104 were allocated to BT and 107 to zolpidem at the first stage. First-stage treatment with BT or zolpidem yielded significant and equivalent benefits for most of the daytime outcomes, including depressive symptoms (Beck Depression Inventory-II mean score change, -3.5 [95% CI, -4.7 to -2.3] vs -4.3 [95% CI, -5.7 to -2.9]), fatigue (Multidimensional Fatigue Inventory mean score change, -4.7 [95% CI, -7.3 to -2.2] vs -5.2 [95% CI, -7.9 to -2.5]), functional impairments (Work and Social Adjustment Scale mean score change, -5.0 [95% CI, -6.7 to -3.3] vs -5.1 [95% CI, -7.2 to -2.9]), and mental health (SF-36 mental health subscale mean score change, 3.5 [95% CI, 1.9-5.1] vs 2.5 [95% CI, 0.4-4.5]), while BT produced larger improvements for anxiety symptoms relative to zolpidem (State-Trait Anxiety Inventory mean score change, -4.1 [95% CI, -5.8 to -2.4] vs -1.2 [95% CI, -3.0 to 0.5]; P = .02; Cohen d = 0.55). Second-stage therapy produced additional improvements for the 2 conditions starting with zolpidem at posttreatment in fatigue (Multidimensional Fatigue Inventory mean score change: zolpidem plus BT, -3.8 [95% CI, -7.1 to -0.4]; zolpidem plus trazodone, -3.7 [95% CI, -6.3 to -1.1]), functional impairments (Work and Social Adjustment Scale mean score change: zolpidem plus BT, -3.7 [95% CI, -6.4 to -1.0]; zolpidem plus trazodone, -3.3 [95% CI, -5.9 to -0.7]) and mental health (SF-36 mental health subscale mean score change: zolpidem plus BT, 5.3 [95% CI, 2.7-7.9]; zolpidem plus trazodone, 2.0 [95% CI, 0.1-4.0]). Treatment benefits achieved at posttreatment were well maintained throughout the 12-month follow-up, and additional improvements were noted for patients receiving the BT treatment sequences. In this randomized clinical trial of adults with insomnia disorder, BT and zolpidem produced improvements for various daytime symptoms of insomnia that were no different between treatments. Adding a second treatment offered an added value with further improvements of daytime functions. ClinicalTrials.gov Identifier: NCT01651442.

Differential effects of sleep deprivation on behavior and microglia in a brain-region-specific manner in young and aged male mice

Microglia, resident immune cells in the central nervous system, constantly monitor the state of the surrounding brain activity. The animal model induced by sleep deprivation (SD) is widely used to study the pathophysiological mechanisms of insomnia and bipolar disorder. However, it remains unclear whether SD affects behaviors in young and aged male mice and microglia in various brain regions. In this study, we confirmed brain region-specific changes in microglial density and morphology in the accumbens nucleus (Acb), amygdala (AMY), cerebellum (Cb), corpus callosum (cc), caudate putamen, hippocampus (HIP), hypothalamus (HYP), medial prefrontal cortex (mPFC), and thalamus (TH) of young mice. In addition, the density of microglia in old mice was higher than that in young mice. Compared with young mice, old mice showed a markedly increased microglial size, decreased total length of microglial processes, and decreased maximum length. Importantly, we found that 48-h SD decreased microglial density and morphology in old mice, whereas SD increased microglial density and morphology in most observed brain regions in young mice. SD-induced hyperactivity was observed only in young mice but not in old mice. Moreover, microglial density (HIP, AMY, mPFC, CPu) was significantly positively correlated with behaviors in SD- and vehicle-treated young mice. Contrarily, negative correlations were shown between the microglial density (cc, Cb, TH, HYP, Acb, AMY) and behaviors in vehicle-treated young and old mice. These results suggest that SD dysregulates the homeostatic state of microglia in a region- and age-dependent manner. Microglia may be involved in regulating age-related behavioral responses to SD.

Differences in Anxiety, Insomnia, and Trauma Symptoms in Wildfire Survivors from Australia, Canada, and the United States of America.

Many survivors of wildfires report elevated levels of psychological distress following the trauma of wildfires. However, there is only limited research on the effects of wildfires on mental health. This study examined differences in anxiety, depression, insomnia, sleep quality, nightmares, and post-traumatic stress disorder (PTSD) symptoms following wildfires in Australia, Canada, and the United States of America (USA). One hundred and twenty-six participants from Australia, Canada, and the USA completed an online survey. The sample included 102 (81%) women, 23 (18.3%) men, and one non-binary (0.8%) individual. Participants were aged between 20 and 92 years (M age = 52 years, SD = 14.4). They completed a demographic questionnaire, the Disturbing Dream and Nightmare Severity Index (DDNSI), Generalized Anxiety Disorder Questionnaire (GAD-7), the Insomnia Severity Index (ISI), Patient Health Questionnaire (PHQ-9), the Pittsburgh Sleep Quality Index (PSQI), and PTSD Checklist (PCL-5). Results showed that participants from the USA scored significantly higher on the GAD-7 (p = 0.009), ISI (p = 0.003), and PCL-5 (p = 0.021) than participants from Australia and Canada. The current findings suggest a need for more international collaboration to reduce the severity of mental health conditions in Australia, Canada, and the USA.

Cognitive behavioural therapy for insomnia reduces actigraphy and diary measured sleep discrepancy for individuals with comorbid insomnia and major depressive disorder: A report from the TRIAD study

Objective/BackgroundDiscrepancies between sleep diaries and actigraphy occur among individuals with insomnia. Cognitive behavioural therapy for insomnia (CBT-I) improves insomnia but the impact on discrepancy is unclear. This study examined CBT-I's effects on actigraphy-diary discrepancy and explored sleep-related beliefs and attitudes as a mediator. Patients/MethodsParticipants were 108 (age M±SD = 47.23 ± 12.42, 67.60 % female) adults with insomnia and major depressive disorder from the Treatment of Insomnia and Depression study. They were randomized to 7 sessions of CBT-I or sham Quasi-Desensitization Therapy for Insomnia (DTI), plus 16 weeks of antidepressants. Two weeks of actigraphy and sleep diary were collected at baseline, mid-treatment, end-treatment. Differences between sleep diary and actigraphy total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency (SE) were calculated. Participants completed Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS) at baseline and mid-treatment. ResultsAt baseline, diary (versus actigraphy) TST was shorter (1.1 ± 1.41h), whilst SOL (21.64 ± 41.25min) and WASO (17.45 ± 61.99min) were longer. Mixed effects models using daily data showed that after adjusting for age and sex, participants in the CBT-I group (versus DTI) showed greater reduction in all actigraphy-diary discrepancy domains (all p-values<.01), reductions evident from mid-treatment. Group differences on actigraphy-diary discrepancy reductions in TST, SOL, and SE (not WASO) were mediated by changes in DBAS from baseline to mid-treatment (all p-values<.05). Changes in discrepancy did not mediate insomnia symptom changes (p-values>.39). ConclusionsCBT-I reduced actigraphy-diary discrepancy in individuals with comorbid insomnia and depression; this reduction was associated with improved sleep-related attitudes, a therapeutic target of CBT-I. Clinical trial registrationTRIAD (Treatment of Insomnia and Depression): Improving Depression Outcome by Adding Insomnia Therapy to Antidepressants. Prospectively registered with Clinical Trials (NCT00767624). Support (if any)MH078924, MH078961, MH079256.

Transitioning insomnia patients from zolpidem to lemborexant: A multicenter, open-label study evaluating a next-dose transition approach to insomnia pharmacotherapy

ObjectiveFew clinical studies have assessed real-world abrupt transitioning between insomnia medications. This study assessed strategies for directly transitioning patients from zolpidem tartrate (ZOL) immediate/extended release to the dual orexin receptor antagonist, lemborexant (LEM). MethodsThis randomized, open-label, multicenter study (Study 312; E2006-A001-312) enrolled 53 adults age ≥18 years with insomnia disorder and ≥1-month history of intermittent (3–4 nights/week) or frequent (≥5 nights/week) ZOL use. Subjects recorded their ZOL use in a 3-week Pretreatment Phase, followed by a 2-week Treatment Phase (TRT; Titration) during which ZOL was discontinued. Intermittent ZOL users transitioned to LEM 5 mg (LEM5), Cohort 1, and frequent ZOL users were randomized 1:1 to LEM5, Cohort 2A, or LEM 10 mg (LEM10), Cohort 2B. One dose adjustment was permitted during the TRT. Subjects completing the TRT could continue LEM in the 12-week Extension Phase (EXT). The primary outcome was proportion of subjects who successfully transitioned and remained on LEM at the end of the TRT. ResultsMost subjects (43 [81.1 %]) successfully transitioned to LEM (9 [90 %], 17 [81.0 %], and 17 [77.3 %] in Cohorts 1, 2A, and 2B, respectively). By the end of the EXT, 66.7 % in Cohort 1 and 60.0 % in Cohort 2A up-titrated to LEM10, whereas 41.2 % in Cohort 2B down-titrated to LEM5; 61.0 % were receiving LEM10 at study end. At the end of the TRT, more subjects taking LEM reported that it helped them return to sleep after waking, compared with those taking ZOL (71.7 % vs. 49.1 %). There were no important differences between treatments regarding how subjects reported feeling as they fell asleep. Most of the treatment-emergent adverse events with LEM were mild in severity. ConclusionsMost subjects transitioned successfully to LEM from ZOL (intermittent or frequent use). LEM was well tolerated.