Insomnia Disorder Research Articles

Orexin Receptor Antagonists for the Prevention and Treatment of Alzheimer's Disease and Associated Sleep Disorders.

Orexins/hypocretins are neuropeptides produced by the hypothalamic neurons, binding two G-protein coupled receptors (orexin 1 and orexin 2 receptors) and playing a critical role in regulating arousal, wakefulness, and various physiological functions. Given the high prevalence of sleep disturbances in Alzheimer's disease (AD) and their reported involvement in AD pathophysiology, the orexin system is hypothesized to contribute to the disease pathogenesis. Specifically, recent evidence suggests that orexin's influence may extend beyond sleep regulation, potentially affecting amyloid-β and tau pathologies. Dual orexin receptor antagonists (DORAs), namely suvorexant, lemborexant, and daridorexant, demonstrated efficacy in treating chronic insomnia disorder across diverse clinical populations. Considering their stabilizing effects on sleep parameters and emerging evidence of a possible neuroprotective role, these agents represent a promising strategy for AD management. This leading article reviews the potential use of orexin receptor antagonists in AD, particularly focusing on their effect in modulating disease-associated sleep disturbances and clinical outcomes. Overall, clinical studies support the use of DORAs to enhance sleep quality in patients with AD with comorbid sleep and circadian sleep-wake rhythm disorders. Preliminary results also suggest that these compounds might influence AD pathology, potentially affecting disease progression. Conversely, research on selective orexin receptor antagonists in AD is currently limited. Further investigation is needed to explore orexin antagonism not only as a symptomatic treatment for sleep disturbances, but also for its broader implications in modifying AD neurodegeneration, emphasizing mechanisms of action and long-term outcomes.

Effect of Trailokya Vijya Vati in Various Disease – A Review

Introduction: One of the strongest traditional medicines is Trailokya Vijaya Vati, which contains vijaya as one of its main constituents. “Trailokya Vijaya Vati” means “victory over the outer three worlds” in literal translation. According to Ayurveda, the medication is considered a “Aashukari” or drug that offers immediate comfort since it directly affects motor neurons, or “Vaat-Vaahini Naadi.” Because of this, it offers prompt relief from conditions involving different kinds of pain. Materials and Methods: Information on trailokya vijya vati in various disease was gathered from the Laghutrayi, the Brihattrayi and its commentaries, and other Ayurvedic and modern texts. Results: The binary preparation known as Trailokya Vijaya Vati, which combines Vijaya sativa with Bambusa arundianaceae, was initially documented in Rasa Vigyana, a modern Ayurvedic Alchemy and Pharmaceutics treatise. Discussion: Apasmara (seizure disorders), Rajahkashtajanya Shoola (dysmenorrhea and related symptoms), Rajayakshma (tuberculosis and similar wasting diseases), Atisara (diarrhea, colitis, IBS, IBDs, etc.), and Shoola (acute and chronic pains emerging from varied pathologies and origins) are just a few of the plethora of health conditions for which this potent formulation is renowned for producing amazing therapeutic effects. Conclusion: Trailokya Vijaya Vati improves general health and well-being by balancing the three doshas (Pitta, Kapha, and Vata) in the body The main constituents in Trailokya Vijaya Vati, a traditional medicine, are Bambusa arundinacea and Vijaya. The Ayurvedic text Rasa Vigyana describes this powerful formulation, which has been shown to have therapeutic effects for a variety of health conditions, such as anxiety, insomnia, seizures, psychological and psychosomatic disorders, dysmenorrhea, diarrhea, tuberculosis, and acute and chronic pain. The medication helps to manage seizures and has a relaxing impact on the brain.[1] Trailokya Vijaya Vati is also effective in relieving neuropathic pain. One kind of persistent pain that results from harm to the nerve system is called neuropathic pain. Trailokya Vijaya Vati’s natural components have the potential to lessen inflammation and ease neuropathic pain. Chemotherapy adverse effects can be effectively mitigated using Trailokya Vijaya Vati. Abdominal pain and renal colic

The Association between Suicidal Ideation and Subtypes of Comorbid Insomnia Disorder in Apneic Individuals.

Background/Objectives: Given the existence of higher suicidality in apneic individuals, this study aimed to determine the potential role played by subtypes of the comorbid insomnia disorder (CID) in the occurrence of suicidal ideation for this specific subpopulation. Methods: To perform our analyses, 1488 apneic individuals were retrospectively extracted from the Sleep Laboratory hospitalization register. Only apneic individuals with suicidal ideation highlighted during the psychiatric interview and/or with a score ≥1 on item G of the Beck Depression Inventory confirmed during the clinical interview were included in the group with suicidal ideation. The likelihood of suicidal ideation associated with CID subtypes was investigated using logistic regression analyses. Results: The prevalence of suicidal ideation was 9.3% in our sample of apneic individuals. After hierarchically introducing the significant confounders for adjustment, multivariate logistic regression analyses demonstrated that unlike short sleep duration alone and CID without short sleep duration, the likelihood of suicidal ideation was only higher for CID with short sleep duration in apneic individuals. Conclusions: Thus, we highlighted in this study that CID with short sleep duration could play a major role in higher suicidality for apneic individuals, which seems to require systematic screening and appropriate treatment of this comorbid sleep disorder to enable better management of suicidal risk in this specific subpopulation.

Aberrant individual large-scale functional network connectivity and topology in chronic insomnia disorder with and without depression

Insomnia is increasingly prevalent with significant associations with depression. Delineating specific neural circuits for chronic insomnia disorder (CID) with and without depressive symptoms is fundamental to develop precision diagnosis and treatment. In this study, we examine static, dynamic and network topology changes of individual large-scale functional network for CID with (CID-D) and without depression to reveal their specific neural underpinnings. Seventeen individual-specific functional brain networks are obtained using a regularized nonnegative matrix factorization technique. Disorders-shared and -specific differences in static and dynamic large-scale functional network connectivities within or between the cognitive control network, dorsal attention network, visual network, limbic network, and default mode network are found for CID and CID-D. Additionally, CID and CID-D groups showed compromised network topological architecture including reduced small-world properties, clustering coefficients and modularity indicating decreased network efficiency and impaired functional segregation. Moreover, the altered neuroimaging indices show significant associations with clinical manifestations and could serve as effective neuromarkers to distinguish among healthy controls, CID and CID-D. Taken together, these findings provide novel insights into the neural basis of CID and CID-D, which may facilitate developing new diagnostic and therapeutic approaches.

Screening for Psychiatric Disorders in Chronic Rhinosinusitis Patients Waiting for Surgery: A Prospective Cross-Sectional Study.

To assess the prevalence of depression, anxiety, insomnia and somatic symptom disorder (SSD) in chronic rhinosinusitis (CRS) patients who were waiting for surgery and to predict these psychiatric disorders using the 22-item Sinonasal Outcome Test (SNOT-22). A prospective cross-sectional study. The rhinology ward at our institution, a tertiary hospital. Adult patients (> 18 years) diagnosed with CRS who were admitted to the rhinology ward for endoscopic sinus surgery and were able to understand and complete the study questionnaires. Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7), Insomnia Severity Index (ISI), Patient Health Questionnaire-15 (PHQ-15) and SNOT-22. Of the 159 participants recruited, 58 were at risk of depression (defined by PHQ-9 > 4, while 25 with PHQ-9 > 9), 49 were at risk of anxiety (defined by GAD-7 > 4, while 25 with GAD-7 > 9), 81 were at risk of insomnia (defined by ISI > 7, while 51 with ISI > 14) and 69 were at risk of SSD (defined by PHQ-15 > 4, while 24 with PHQ-15 > 9). The SNOT-22 score was closely correlated with the scores of psychometric tests and was an independent predictor of these psychiatric disorders. Patients with a high SNOT-22 score (> 30) are likely to be affected by comorbid psychiatric disorders and should be further evaluated by otolaryngologists. Depression, anxiety, insomnia and SSD are prevalent in CRS patients. Otolaryngologists should have a low threshold to ask the patient about psychiatric symptoms, especially for patients with an SNOT-22 score > 30.

Prevalence of sleep disorders and association with various occupations among Indian population aged ≥ 45 years: Insight from Longitudinal Ageing Study in India (LASI)

ABSTRACT Introduction: By scrutinizing the impact of job schedules, workplace culture and stress levels, our study aims to determine the prevalence of sleep disorders among various occupations and its associated factors. The findings promise to enhance the overall well-being, sleep quality and productivity in various occupational settings. Methods: This is an analytical cross-sectional study involving secondary data from the nationally representative Longitudinal Ageing Study in India (LASI Wave I 2017-18) of 35 Indian states and union territories with exception of Sikkim. The study included 59441 Indian volunteers who older than 45 years. Multivariable logistic regression analysis was conducted to study the association of sleep disorders among various occupations while accounting for other associated factors. Results: Prevalence of sleep disorders was higher among the females (12.66%), unemployed (13.34%), ≥ 60-yr age group (13.45%), those who lived in rural areas (12.35%), those who were illiterate (12.80%) and reported themselves to be widowed, separated or divorced (14.54%), people with no health insurance (11.74%), smokers (12.11%), without physical activity (12.67%) and also rated themselves as poor in the self-rated health status (26.77%). Alcohol consumption was not statistically significant factor for sleep disorders. Conclusions: There is an emerging need for targeted screening, prompt detection and early management of insomnia and other sleep disorders among the high-risk groups. Provision of accessible and affordable screening tools, training skills for early diagnosis at primary care level and/or proper referral services to higher centres form the cornerstone for adequate management of sleep disorders.

Prevalence of insomnia and use of sleep aids among adults in Canada

ObjectivesTo estimate the prevalence of insomnia and the use of sleep aids among Canadian adults. MethodsData were derived from a phone interview conducted (April to October 2023) with a stratified, population-based sample of 4037 adults (57.6 % females; mean age 50.6 ± 18.4; range 18–102 years old) living in Canada. Post-stratified survey weights were included in the analysis to ensure the representativity of the adult Canadian population. ResultsThe prevalence estimate of insomnia disorder was 16.3 % (95 % CI 15.1–17.6), with higher rates in females (risk ratio [RR] 1.24, 95 % CI 1.06–1.45), Indigenous peoples (RR 1.77, 95 % CI 1.27–2.47), and individuals with poorer mental or physical health. Overall, 14.7 % of respondents reported having used prescribed sleep medications in the previous 12 months, 28.7 % used natural products or over-the-counter (OTC) sleep aids, 15.6 % used cannabis-derived products and 9.7 % used alcohol for sleep in the last 12 months. Higher proportions of females used prescribed medication (RR 1.79, 95 % CI 1.31–2.43) and natural products or OTC medication (RR 1.41, 95 % CI 1.16–1.71), while more males used cannabis (RR 1.33, 95 % CI 1.03–1.72) and alcohol (RR 1.67, 95 % CI 1.16–2.33) for sleep. Higher proportions of older adults (≥65 years) were taking prescribed medications, while more young adults (18–35 years) used natural products or OTC medications, cannabis, and alcohol as sleep aids. ConclusionsInsomnia is a highly prevalent condition in Canada and there is widespread and increasing use of various medications and substances to cope with this health issue. These findings highlight the need for public health interventions to promote healthy sleep and for wider dissemination of evidence-based treatments for insomnia, such as cognitive behavioral therapy which is the first-line treatment for insomnia in practice guidelines, to reduce sleep health disparities.

Adis Summary of Research: Number, duration, and distribution of wake bouts in patients with insomnia disorder: effect of daridorexant and zolpidem

Adis Summary of Research: Number, duration, and distribution of wake bouts in patients with insomnia disorder: effect of daridorexant and zolpidem

Hyperarousal dynamics reveal an overnight increase boosted by insomnia

Hyperarousal is a key symptom of anxiety, stress-related disorders, and insomnia. However, it has been conceptualized in many different ways, ranging from various physiological markers (e.g. cortisol levels, high-frequency EEG activity) to personality traits, or state assessments of subjective anxiety and tension. This approach resulted in partly inconsistent evidence, complicating unified interpretations. Crucially, no previous studies addressed the likely variability of hyperarousal within and across days, nor the relationship of such variability in hyperarousal with the night-by-night variability in sleep quality characteristic of insomnia.Here, we present a novel data-driven approach to understanding dynamics of state hyperarousal in insomnia. Using ecological momentary assessment, we tracked fluctuations in a wide range of emotions across 9 days in 169 people with insomnia disorders and 38 controls without sleep problems. Exploratory factor analysis identified a hyperarousal factor, comprised of items describing tension and distress. People with insomnia scored significantly higher on this factor than controls at all timepoints. In both groups, the hyperarousal factor score peaked in the morning and waned throughout the day, pointing to a potential contributing role of sleep or other circadian processes. Importantly, the overnight increase in hyperarousal was stronger in people with in insomnia than in controls. Subsequent adaptive LASSO regression analysis revealed a stronger overnight increase in hyperarousal across nights of worse subjective sleep quality.These findings demonstrate the relationship between subjective sleep quality and overnight modulations of hyperarousal. Disorders in which hyperarousal is a predominant complaint might therefore benefit from interventions focused on improving sleep quality.

Lectin YKL-40 Level and Telomere Length are Indicators of Insomnia Disorder.

To explore the relationship between YKL-40 level, telomere length, and different subtypes of insomnia disorder. A total of 145 individuals suffering from insomnia were enrolled and divided into four groups according to the insomniac subtypes: difficulty initiating sleep, early morning awakening, difficulty maintaining sleep, and mixed symptoms. Eighty healthy controls were also collected at the same time. Peripheral leukocyte genomic DNA was extracted, relative telomere lengths were measured using the real-time quantitative polymerase chain reaction method, and YKL-40 levels were determined using enzyme-linked immunoassay. Logistic regression modeling was used to analyze the correlation between different insomnia subtypes, YKL-40 level, and telomere length. People with telomere lengths in the lowest tertile were more likely to have trouble falling asleep (odds ratio (OR) 2.13, 95% confidence interval (CI) 1.22-3.63; p = 0.03) and had a higher frequency of mixed symptoms (OR 1.49, 95% CI 1.30-2.81; p = 0.04). People in the highest tertile of YKL-40 level had an increased chance of waking up early (OR 2.98, 95% CI 1.54-5.33; p = 0.01) and more mixed symptoms (OR 1.47, 95% CI 1.22-2.79; p = 0.02). Furthermore, using receiver operating characteristic curve analysis, the area under the curve of YKL-40 level and telomere length was 0.806 and 0.746, respectively. Telomere length in patients with difficulty initiating sleep and mixed symptoms was significantly shortened and the level of YKL-40 in people who have early morning awakening and mixed symptoms was significantly increased. Our findings provide the first evidence that leukocyte telomere length and YKL-40 level are individually linked to mixed symptoms.

Epidemiology and burden of chronic insomnia disorder in Europe: an analysis of the 2020 National Health and Wellness Survey

Introduction Chronic insomnia disorder (CID) is considered a significant worldwide public health concern; however, its exact burden is unknown. We estimate its prevalence across France, Germany, Italy, Spain, and the United Kingdom, and assess the economic and humanistic burden for a broader insomnia population. Methods This retrospective, cross-sectional, observational study used 2020 National Health and Wellness Survey (NHWS) data. Patients reporting insomnia were characterized to define CID. Health-related quality of life (HRQoL), work productivity, and healthcare resource use (HCRU) outcomes were assessed in four cohorts according to insomnia diagnosis and treatment status and examined using multivariable analyses according to Insomnia Severity Index categories. Results Among 62,319 respondents, 9,035 (21.2%) reported experiencing insomnia over the previous 12 months. CID prevalence rates were 5.5% to 6.7% across the five countries and 6.0% overall. HRQoL outcomes were persistently poorer in cohorts of patients diagnosed with insomnia than those with undiagnosed insomnia. Undiagnosed and treated insomnia patients reported the highest work presenteeism and total work productivity impairment and the highest number of emergency room and hospitalization visits than patients with insomnia (either treated or untreated). After adjusting for covariates, patients with severe insomnia reported significantly worse EQ-5D-5L utility scores, higher absenteeism and presenteeism rates, and more healthcare provider visits over the past 6 months than patients without insomnia (all p < 0.01). Conclusions Our prevalence rates for CID align with published literature. A diagnosis of insomnia, use of sleep medications, and severity of insomnia are associated with poor quality of life, loss of work productivity, and higher HCRU, confirming the high unmet need and substantial humanistic and economic burden of CID.

Exploring Sleep Architecture in Polish Patients with Multiple Sclerosis: A Polysomnography Study.

Sleep disturbances are a prevalent phenomenon in patients with multiple sclerosis (PwMS). The present study employs polysomnography (PSG) to quantify sleep efficiency and architecture in PwMS, aiming to elucidate the relationships between PSG parameters and factors including gender, disability level, brain lesion location, and subjective measures of insomnia, excessive daytime sleepiness (EDS), fatigue, pain, and mood disorders. The study cohort comprised 51 adult PwMS, of whom 31 underwent overnight PSG. The demographic and clinical characteristics, including age, gender, and Expanded Disability Status Scale (EDSS), were collated. The Athens Insomnia Scale, the Epworth Sleepiness Scale, the Fatigue Severity Scale, the Modified Fatigue Impact Scale (MFIS), the Numerical Pain Rating Scale, and the Hospital Anxiety and Depression Scale were employed for the assessment of insomnia, EDS, fatigue, pain, and mood disorders. The brain and spinal cord magnetic resonance imaging (MRI) were evaluated. A reduced sleep efficiency was observed among 30 PwMS (aged 38.9 ± 12.9), with a mean of 80 ± 12%, especially in those with brainstem demyelinating lesions. In those PwMS aberrant sleep onset latency (SOL) and wake after sleep onset were also noted (p < 0.05). The prevalence of sleep fragmentation, as measured by the total arousal index, was greater in male PwMS than in female (p < 0.05). Higher disability according to the EDSS correlated with longer SOL (ρ = 0.48, p < 0.05), and reduced N2 sleep stage correlated with cognitive fatigue according to MFIS (ρ = -0.46, p < 0.05). Age, disease duration, insomnia, EDS, physical fatigue, and mood disorders did not impact PSG parameters. The study demonstrated the disruption of sleep architecture in PwMS, and highlighted the importance of a comprehensive PSG assessment of sleep disturbances in this population.

Increase in short-term and long-term stress-associated mental illness after Jiji earthquake in Taiwan: A twenty-year longitudinal population-based cohort study (1999–2019)

BackgroundEarthquakes have caused profound physical and mental health impacts in human history. The Jiji earthquake, which had a magnitude of 7.6 on the Richter scale, occurred on 21 September 1999 in Taiwan. A close follow-up on the mental health status of affected adults after major natural disasters to construct the short-term and long-term risk and prevalence of stress-associated mental illnesses has not been performed by using the nationwide health databases. MethodsThis population-based cohort study included 468,804 adults affected by Jiji earthquake spanning from 2000 to 2019 who were matched at a 1:4 ratio with unaffected individuals based on age and sex (n = 1,875,216). Employing a subdistribution hazard regression analysis, we assessed the incidence of sleep, anxiety, and depressive disorders after Jiji earthquake. Corrections for multiple comparisons were carried out using the Benjamini–Hochberg procedure. ResultsAffected adults experienced an increased incidence of short-term (approximately twice) stress-associated psychiatric disorders. The risk of the post-traumatic stress disorder (PTSD) is significantly higher in the affected adults (40–64 years: aSHR: 92.0; ≥65 years: aSHR: 96.7, p < 0.0001). Middle-aged (aged 40–64 years) male adults presented with significantly more short-term (< one year) and long-term (up to 20 years) stress-related mental illnesses, i.e., insomnia, anxiety, and depressive disorders, than individuals in the control group. ConclusionsAn earthquake has significant short and long-term effects on sleep quality, anxiety, and depressive disorders in affected adults. Optimal short and long-term close monitoring is needed to deploy medical resources and socioeconomic support to relieve mental stress burdens.

A Retrospective Observational Study to Understand Medication Utilization and Lines of Treatment in Patients With Insomnia Disorder.

A Retrospective Observational Study to Understand Medication Utilization and Lines of Treatment in Patients With Insomnia Disorder.

Restoration of abnormal sleep EEG power in patients with insomnia disorder after 1Hz rTMS over left DLPFC.

Hyperarousal has been a significant pathophysiological theory related to insomnia disorder (ID), characterized by excessive cortical activation and abnormal electroencephalogram (EEG) power during daytime or sleep. However, there is currently insufficient attention to the EEG power during rapid eye movement (REM) sleep and different stages of non-rapid eye movement (NREM) sleep. Additionally, whether the abnormal sleep EEG power in ID patients can be restored by repetitive transcranial magnetic stimulation (rTMS) remains unclear. Data of 26 ID patients and 26 healthy controls (HCs) were included in the current observational study. The comparisons of relative power between patients and HCs at baseline in each band of each sleep stage and the changes in patients before and after rTMS treatment were performed. The correlations between relative power and behavioral measures of the patients were also investigated. Abnormalities in sleep EEG relative power in the delta, beta and gamma bands of the patients were observed in NREM2, NREM3 and REM sleep. Correlations were identified between relative power and behavioral measures in ID group, primarily encompassing sleep efficiency, sleep onset latency and depression scores. Post-treatment improvements in relative power of the delta and beta band were observed in NREM2 sleep. The relative power of sleep EEG exhibited a significant correlation with sleep measures in ID patients, and demonstrated notable differences from HCs across the delta, beta, and gamma frequency bands. Furthermore, our findings suggest that rTMS treatment may partially ameliorate relative power abnormalities in patients with ID.

Incidence of psychiatric disorders after total knee or hip arthroplasty by anesthesia type: A nationwide cohort study

BackgroundEvidence is lacking of an association between anesthetic choice and the risk of psychiatric disorders. Therefore, this study aimed to examine the impact of regional anesthesia (R/A) versus general anesthesia (G/A) on the occurrence of psychiatric disorders in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA). MethodsData for this population-based cohort study were sourced from the National Health Insurance Service of South Korea. The study included adult patients who underwent TKA or THA between January 1, 2016, and December 31, 2021. The endpoint was the diagnosis of postoperative psychiatric disorders within 1 year postoperative. ResultsThis study included 411,967 patients who underwent THA or TKA. Among them, 290,476 (70.5 %) underwent THA or TKA under R/A (R/A group), while 121,491 (29.5 %) underwent THA or TKA under G/A (G/A group). In multivariate logistic regression, the R/A group had an 8 % lower incidence of postoperative psychiatric disorders (odds ratio [OR], 0.92; 95 % confidence interval [CI], 0.90–0.94; P < 0.001) than the G/A group. Specifically, a lower incidence of postoperative psychiatric disorder for depression (OR, 0.89; 95 % CI, 0.86–0.92; P < 0.001), bipolar disorder (OR, 0.88; 95 % CI, 0.83–0.94; P < 0.001), anxiety disorder (OR, 0.95; 95 % CI, 0.92–0.98; P = 0.001), and insomnia disorder (OR, 0.95; 95 % CI, 0.80–1.11; P = 0.496) was observed in the R/A versus G/A group. ConclusionsAmong these South Korean patients who underwent TKA or THA, the R/A group had a lower incidence of postoperative psychiatric disorders than the G/A group.

Effects of mindfulness-based music listening on conflict control in young adults with insomnia disorder: behavioral and event-related potential evidence.

Insomnia Disorder (ID) has become the second most prevalent mental disorder, with significant negative effects on daytime cognitive functions. Previous studies suggested that mindfulness-based music listening (MBML) can effectively improve conflict control and attentional processing in healthy adults. However, the behavioral and neurophysiological characteristics of MBML in young adults with ID remain unclear. To explore the behavioral and neurophysiological characteristics of MBML in regulating negative emotions among young Chinese adults with ID, 60 young adults with ID were asked to complete an emotion-word Stroop task under three mood states while recording event-related potentials (ERPs). Task and questionnaire results showed that (1) negative emotion induced by the negative simulated video significantly suppressed the attentional processing of emotional faces and words in the conflict control task among young people with ID, (2) MBML reduced cognitive and physical arousal levels, enhanced positive mood, and improved attentional control abilities in young adults with ID. The ERP results showed that a greater N3 effect and the smaller P3 and late positive component (LPC) effects reflected that MBML effectively regulated negative emotions induced by the negative simulated video and attentional processing abilities for conflict control in young adults with ID. Maintaining mindfulness while listening to music may enhance positive emotional experiences and improve cognitive ability, and exhibit larger N3 effects and smaller P3 and LPC effects in the electrophysiology mechanism, with a reduction in the hyperarousal level in young adults with insomnia disorders.

Nurse-Supported Self-Directed Cognitive Behavioral Therapy for Insomnia

Cognitive behavioral therapy for insomnia (CBTi) is the standard of care for treating insomnia disorder, but access is limited. Alternative approaches are needed to expand access to the standard of care. To examine the effectiveness of a nurse-supported, self-directed behavioral insomnia intervention for decreasing insomnia severity and improving sleep outcomes among veterans, a population with considerable mental health comorbidity. This randomized clinical trial included 178 patients with insomnia disorder who were recruited from a Veterans Affairs hospital (Durham VA Healthcare System) from September 2019 to April 2022 and randomized following baseline assessment; follow-ups were conducted at 8 weeks (primary end point) and 6 months. Data analysis was primarily conducted during the summer of 2023 and concluded in May 2024. Six weekly phone calls from a nurse interventionist plus assigned treatment manual readings covering CBTi treatment components. The health education manual focused on health topics but not sleep. The primary outcome was the Insomnia Severity Index (score range, 0-28; remission <8; differential improvement of 3 points targeted) score assessed at 8 weeks postrandomization. Secondary outcomes were sleep outcomes, depression, fatigue, treatment response, and remission. Of 178 study participants, the mean (SD) age was 55.1 (13.2) years, and 128 (71.9%) identified as men. At 8 weeks, Insomnia Severity Index scores decreased by an estimated mean (SE) of 5.7 (0.51) points in the intervention group and 2.0 (0.47) points in the control group, a differential mean improvement of 3.7 points (95% CI, -5.0 to -2.4; P < .001). Differences were sustained at 6 months (mean, -2.8; 95% CI, -4.4 to -1.3; P < .001). The intervention also resulted in greater improvements at 8 weeks postrandomization in diary sleep onset latency, wake after sleep onset, and sleep efficiency and actigraphy sleep efficiency; these differences were sustained at 6 months. At 8 weeks, depression and fatigue were significantly reduced, and the odds of treatment response and remission were greater in the intervention group compared with controls. This randomized clinical trial found that despite greater prevalence of mental health conditions and sleep difficulties among veterans, a nurse-supported self-directed CBTi was more effective than health education control for reducing insomnia severity and improving sleep outcomes. Although less effective than therapist-delivered CBTi, findings were comparable with other trials using modified CBTi protocols. ClinicalTrials.gov Identifier: NCT03727438.

The Abnormal N-Acetylaspartate to Creatine Ratio of the Right Putamen is Linked to Wakefulness in Patients with Insomnia Disorder.

Converging evidence implicates the putamen in sleep-wake regulation. However, its role remains unclear. We hypothesized that metabolic abnormalities in the putamen are linked to insomnia disorder, which has not been previously addressed, and investigated putaminal N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) in patients with insomnia disorder compared to healthy controls. In the present study, the concentrations of NAA, Cho, and Cr in the putamen of 23 patients with insomnia disorder and 18 healthy controls were determined using proton magnetic resonance spectroscopy. Sociodemographic, psychometric, and polysomnography data were obtained from all participants. We found that the mean NAA/Cr ratio of the right putamen was significantly greater in the insomnia group compared to the control group and also greater than the left putamen within the insomnia group. The NAA/Cr ratio of the right putamen distinguished insomnia disorder from normal sleep with 78.3% sensitivity and 61.1% specificity. Furthermore, this ratio positively correlated with both objective and subjective insomnia severity and sleep quality. Our findings provide critical evidence for the dysfunctional putaminal metabolism of NAA/Cr in insomnia disorder, suggesting that the abnormal NAA/Cr ratio of the right putamen is linked to wakefulness in patients with insomnia disorder and may serve as a potential biomarker of insomnia disorder.

Beta-Myrcene as a Sedative-Hypnotic Component from Lavender Essential Oil in DL-4-Chlorophenylalanine-Induced-Insomnia Mice.

With the increasing prevalence of insomnia-related diseases, the effective treatment of insomnia has become an important health research topic. Lavender (Lavandula angustifolia Mill.) essential oil (LEO) is a commonly used medicine for the treatment of insomnia and neurological disorders. However, neither the active components nor its sedative-hypnotic mechanism have been fully discovered. This study aimed to screen the main active terpenes and discover the possible mechanism of LEO through network pharmacology in the treatment of insomnia-related diseases, as well as to verify our hypothesis in insomnia mice. The results showed that, in LEO's 15 potential active ingredients, beta-myrcene had strong sedative-hypnotic effects through the serotonergic synaptic pathway according to the network pharmacological prediction. Further, PCPA(DL-4-chlorophenylalanine)-induced insomnia mice were treated with beta-myrcene for one day or seven days. The quiet state of insomnia mice was increased effectively, and the hypnotic effect was enhanced by anaobarbital sodium by prolonging sleep duration, decreasing sleep latency, and increasing the rate of falling asleep. Beta-myrcene reduced the damage to hypothalamic neuron cells induced by PCPA and increased neurotransmitter levels of GABA, 5-HT, and Glu in the serum and hypothalamus of insomnia mice. Meanwhile, beta-myrcene exerted an improvement in insomnia by upregulating relevant genes and protein expression in the serotonergic synaptic pathway. These results support the merit of the sedative-hypnotic activity of LEO. Beta-myrcene, a terpene in LEO, may be the main source of its sedative-hypnotic properties. It may serve as a good potential compound in future clinical studies on coping with insomnia.