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Background: Chronic Insomnia Disorder (CID) is highly prevalent among older adults and impairs cognitive function. Insomnia accelerates the progression of mild cognitive impairment (MCI) and increases the risk of developing dementia. Acupuncture has been demonstrated in improving sleep quality and cognitive function. This study aims to explore the functional brain characteristics of CID with MCI patients and to assess the effects of acupuncture therapy using functional near-infrared spectroscopy (fNIRS). Methods and design: This study is a single-center randomized controlled trial. Participants will be randomly assigned to the manual acupuncture group or the placebo acupuncture group for an 8-week intervention period. fNIRS data will be collected during resting test and working memory test at baseline and at end of the intervention. The primary outcome is the change of the Montreal Cognitive Assessment (MoCA) score, secondary outcomes include the change of Mini-Mental State Examination (MMSE), Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and Apathy Evaluation Scale-Informant (AES-I). Discussion: The results of the study will provide insights into the effects of acupuncture on sleep quality and cognitive performance in CID with MCI patients. By utilizing fNIRS technology, we will elucidate the neural functional characteristic underlying the therapeutic benefits of acupuncture. Clinical trial registration: https://ClinicalTrials.gov, identifier ChiCTR2300076182. [ABSTRACT FROM AUTHOR]

Chronic insomnia disorder (CID) is a multidimensional disease that may influence various levels of brain organization, spanning the macroscopic structural connectome to microscopic gene expression. However, the connection between genomic variations and morphological alterations in CID remains unclear. Here, we investigated brain structural changes in CID patients at the whole‐brain level and whether these link to transcriptional characteristics. Brain structural data from 104 CID patients and 102 matched healthy controls (HC) were acquired to examine cortical structural alterations using morphometric similarity (MS) analysis. Partial least squares (PLS) regression and transcriptome data from the Allen Human Brain Atlas were used to extract genomes related to MS changes. Gene‐category enrichment analysis (GCEA) was used to identify potential molecular mechanisms behind the observed structural changes. We found that CID patients exhibited MS reductions in the parietal and limbic regions, along with enhancements in the temporal and frontal regions compared to HCs (pFDR <.05). Subsequently, PLS and GCEA revealed that these MS alterations were spatially correlated with a set of genes, especially those significantly correlated with excitatory and inhibitory neurons and chronic neuroinflammation. This neuroimaging‐transcriptomic study bridges the gap between cortical structural changes and the molecular mechanisms in CID patients, providing novel insight into the pathophysiology of insomnia and targeted treatments. The association between genomics and brain structural changes in chronic insomnia disorder is not well understood. Imaging transcriptional analysis bridges the gap between cortical structural changes and molecular mechanisms. Integrating neuroimaging and gene expression data, our work indicates that structural changes in chronic insomnia may be related to chronic neuroinflammation and imbalances between excitatory and inhibitory neuronal activities. [ABSTRACT FROM AUTHOR]

Background: As the most common sleep disorder, chronic insomnia disorder (CID) has become a global health burden to the public. However, it remains unclear about the pathogenesis of this disease. Epigenetic changes may provide important insights into the gene-environment interaction in CID. Therefore, this study was conducted to investigate the DNA methylation pattern in CID and reveal the epigenetic mechanism of this disease. Methods: In this study, whole blood DNA was extracted from 8 CID patients (the CID group) and 8 healthy controls (the control group), respectively. Besides, genome-wide DNA methylation was detected by Illumina Human Methylation 850 K Beadchip. Moreover, the sleep quality and insomnia severity were evaluated by the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI), respectively. Results: A total of 369 differentially methylated positions (DMPs) and 23 differentially methylated regions (DMRs) were identified between the CID and control groups. LHX6 was identified as the most important differentially methylated gene (DMG). The Gene Ontology (GO) analysis results corroborated that DMPs were significantly enriched in 105 GO terms, including cell signaling, homogenous cell adhesion of plasma membrane adhesion molecules, nervous system development, cell adhesion, and calcium ion binding. In addition, it was demonstrated that DMPs were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including the hippo signaling pathway, Ras signaling pathway, and vitamin B6 metabolism. The DMR-related GO analysis results revealed the positive regulation of protein kinase activities. Conclusions: DNA methylation plays a critical role in the development of CID, and LHX6 is validated to be an important DMG. [ABSTRACT FROM AUTHOR]

Ke Yu,1 Lan Xia,1 Hui-Hui Chen,1 Tian-Tian Zou,1 Yu Zhang,1 Ping Zhang,1 Ye Yang,1 Ru-Meng Wei,1 Zeng-Feng Su,2 Gui-Hai Chen1 1Department of Neurology (Sleep Disorder), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei (Chaohu), Anhui Province, 238000, People’s Republic of China; 2Department of General Practice, The Affiliated Chaohu Hospital of Anhui Medical University, Hefei (Chaohu), Anhui Province, 238000, People’s Republic of ChinaCorrespondence: Gui-Hai Chen, Department of Neurology (Sleep Disorders), The Affiliated Chaohu Hospital of Anhui Medical University, Hefei (Chaohu), 238000, People’s Republic of China, Email doctorcgh@163.com Zeng-Feng Su, Department of General Practice, The Affiliated Chaohu Hospital of Anhui Medical University, Hefei (Chaohu), 238000, Anhui Province, People’s Republic of China, Email suzengfeng@163.comPurpose: The purpose of this study was to look into the relationship between pre-sleep arousal state, sleep reactivity, and serum levels of neuroendocrine hormones (cortisol, copeptin, and corticotropin-releasing hormone) in patients with chronic insomnia disorders (CID), and whether the effects of sleep reactivity and pre-sleep arousal on insomnia are related to the levels of these neuroendocrine hormones.Patients and Methods: This study included 61 CID patients and 27 healthy controls (HC) whose base data were matched to those of the CID patients. The Pittsburgh Sleep Quality Index(PSQI), Pre-Sleep Arousal Scale (PSAS), and the Ford Insomnia Response to Stress Test (FIRST) were used to evaluate the participants’ sleep, stress, and neuropsychological function. We measured the participants’ serum concentration levels of cortisol, copeptin, and corticotropin-releasing hormone (CRH), using quantitative sandwich enzyme-linked immunosorbent assays.Results: The CID group had significantly greater serum levels of copeptin, CRH, and cortisol, as well as higher FIRST and PSAS scores than the HC group. The partial correlation analysis revealed a substantial and positive association among cortisol, CRH, copeptin PSQI, PSAS, and FIRST after adjusting for sex, age, depression, and cognition. Principal component analysis showed that PSQI, FIRST, and PSAS, as well as cortisol, CRH, and copeptin, were all loaded on factor 1.Conclusion: Patients with CID showed increased sleep reactivity and pre-sleep arousal, which correlated with serum levels of cortisol, copeptin, and CRH. Changes in neuroendocrine hormone levels may influence how pre-sleep arousal and sleep reactivity affect the development of insomnia.Keywords: chronic insomnia disorder, pre-sleep arousal, sleep reactivity, hormones, neuroendocrine

Abstract Background The hypothalamus has been recognized as a core structure in the sleep-wake cycle. However, whether the neuroplasticity of the hypothalamus is involved in the acupuncture treatment of insomnia remains elusive. Methods We recruited 42 patients with chronic insomnia disorder (CID) and 23 matched healthy controls (HCs), with CID patients randomly assigned to receive real acupuncture (RA) or sham acupuncture (SA) for four weeks. Insomnia severity was evaluated using the Pittsburgh Sleep Quality Index (PSQI) score, and the resting-state functional connectivity (rsFC) of the hypothalamus was assessed via functional magnetic resonance imaging (fMRI). Results In the cross-sectional investigation, CID patients showed increased rsFC between the medial hypothalamus (MH) and left lateral orbital frontal cortex (LOFC), and bilateral medial orbital frontal cortex (MOFC) compared to HCs. In the longitudinal experiment, PSQI scores significantly decreased in the RA group (p = 0.03) but not in the SA group. Interestingly, the increased MH-LOFC connectivity was found to be reduced following RA treatment. In addition, the altered rsFC of MH-LOFC significantly correlated with clinical improvement in the RA group (r = -0.692, p = 0.006). Conclusion This randomized neuroimaging study provides preliminary evidence that acupuncture may improve insomnia symptoms by restoring circuits associated with hypothalamic subregions. Trial registration This trial has been registered on the Chinese Clinical Trial Registry ( www.chictr.org.cn ) with the identifier (ChiCTR1800017092). Registered date: 11/07/2018.

Background: The hypothalamus has been recognized as a core structure in the sleep-wake cycle. However, whether the neuroplasticity of the hypothalamus is involved in the acupuncture treatment of insomnia remains elusive. Methods: We recruited 42 patients with chronic insomnia disorder (CID) and 23 matched healthy controls (HCs), with CID patients randomly assigned to receive real acupuncture (RA) or sham acupuncture (SA) for four weeks. Insomnia severity was evaluated using the Pittsburgh Sleep Quality Index (PSQI) score, and the resting-state functional connectivity (rsFC) of the hypothalamus was assessed via functional magnetic resonance imaging (fMRI). Results: In the cross-sectional investigation, CID patients showed increased rsFC between the medial hypothalamus (MH) and left lateral orbital frontal cortex (LOFC), and bilateral medial orbital frontal cortex (MOFC) compared to HCs. In the longitudinal experiment, PSQI scores significantly decreased in the RA group (p = 0.03) but not in the SA group. Interestingly, the increased MH-LOFC connectivity was found to be reduced following RA treatment. In addition, the altered rsFC of MH-LOFC significantly correlated with clinical improvement in the RA group (r = -0.692, p = 0.006). Conclusion: This randomized neuroimaging study provides preliminary evidence that acupuncture may improve insomnia symptoms by restoring circuits associated with hypothalamic subregions. Trial registration: This trial has been registered on the Chinese Clinical Trial Registry (www.chictr.org.cn) with the identifier (ChiCTR1800017092). Registered date: 11/07/2018. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the comparative efficacy and acceptability of cognitive behavioral therapy for insomnia (CBT‐I), pharmacotherapy, and their combination in the long and short terms among adults with chronic insomnia disorder. Methods: We searched multiple databases to December 27, 2023. We included trials in hypnotic‐free adults with chronic insomnia comparing at least two of CBT‐I, pharmacotherapy, or their combination. We assessed the confidence in evidence using CINeMA. The primary outcome was long‐term remission. Secondary outcomes included all‐cause dropout and self‐reported sleep continuity measures in the long term, and the same outcomes in the short term. We performed frequentist random‐effects network meta‐analyses (CRD42024505519). Findings: We identified 13 trials including 823 randomized participants (mean age, 47.8 years; 60% women). CBT‐I was more beneficial than pharmacotherapy in the long term (median duration, 24 weeks [range, 12 to 48 weeks]; remission odds ratio, 1.82 [95% confidence interval (CI), 1.15–2.87]; [certainty of evidence: high]), while there was weaker evidence of benefit of combination against pharmacotherapy (1.71 [95% CI, 0.88–3.30: moderate]) and no clear difference of CBT‐I against combination (1.07 [95% CI, 0.63–1.80: moderate]). CBT‐I was associated with fewer dropouts than pharmacotherapy. Short‐term outcomes favored CBT‐I over pharmacotherapy except total sleep time. Given the average long‐term remission rate in the pharmacotherapy‐initiating arms of 28%, CBT‐I resulted in a long‐term remission rate of 41% (95% CI, 31%–53%) and combination 40% (95% CI, 25%–56%). Interpretation: The current study found that starting with CBT‐I for chronic insomnia leads to better outcomes than pharmacotherapy. Combination may be better than pharmacotherapy alone, but unlikely to be worth the additional burden over CBT‐I alone. [ABSTRACT FROM AUTHOR]

Summary This study investigated the altered neural activation underlying cognitive control under emotional and sleep‐related interference conditions and its role in subjective sleep disturbance in patients with chronic insomnia disorder. In total, 48 patients with chronic insomnia disorder, and 48 age‐, sex‐ and body mass index‐matched controls were included in this study. They completed self‐reported questionnaires to assess subjective sleep and emotional distress. A sleep diary was used to evaluate subjective sleep parameters. All participants performed the emotional Stroop task (three blocks each of negative emotional, sleep‐related, and neutral words) during functional magnetic resonance imaging assessments. We compared brain activation during the emotional Stroop task between the two groups. We also analysed the correlations between altered neural activation and sleep variables. Less neural activation was detected in the right anterior prefrontal cortex of patients with chronic insomnia disorder than in controls when performing the emotional Stroop task with negative emotional words. The decrease in neural activation was negatively correlated with scores on Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Dysfunctional Beliefs and Attitudes about Sleep Scale. In contrast, they were positively correlated with subjective total sleep time and sleep efficiency as reported in sleep diaries. A decrease in right anterior prefrontal cortex activity under the negative emotional words condition of the emotional Stroop task in patients with chronic insomnia disorder suggests a failure of top‐down inhibition of negative emotional stimuli. This failure induces disinhibition of cognitive hyperarousal, manifested as rumination or intrusive worries, and potentially causing subjective sleep disturbances. [ABSTRACT FROM AUTHOR]

BackgroundTo date， pharmacologic therapy is considered the standard first-line treatment for insomnia disorder， but there are still some concerns over the adverse reactions. Repetitive transcranial magnetic stimulation （rTMS） and cognitive behavioral therapy for insomnia （CBT-I） as an alternative to pharmacologic therapy have the advantages of fewer side effects and better patient tolerance in the treatment of chronic insomnia disorder.ObjectiveTo explore the clinical efficacy of rTMS and CBT-I on chronic insomnia disorder， so as to provide a novel therapeutic option for the treatment of chronic insomnia disorder.MethodsA total of 50 patients with chronic insomnia disorder attending the outpatient clinic of Inner Mongolia Autonomous Region Mental Health Center or community hospital from September 21， 2020 to December 16， 2021 and fulfilling the International Classification of Sleep Disorders， third edition （ICSD-3） diagnostic criteria were enrolled. Additionally， 16 age- and sex-matched healthy controls recruited from the community were set as control group. Patients were randomly divided into rTMS group and CBT-I group， 25 cases in each group， and received rTMS or CBT-I intervention for 6 weeks respectively. At enrollment and completion of intervention， patients were subjected to Polysomnography （PSG）， Pittsburgh Sleep Quality Index （PSQI）， Insomnia Severity Index （ISI） and Repeatable Battery for the Assessment of Neuropsychological Status （RBANS）. All participants underwent resting-state functional magnetic resonance imaging （rs-fMRI） scans， and amplitude of low-frequency fluctuation （ALFF） was calculated. The brain regions with statistically different ALFF values between patient group and control group were chosen as regions of interest （ROIs）， and whole-brain seed-based functional connectivity analyses were conducted.ResultsAfter a 6-week intervention in the two groups， the main effect of time was significant for PSQI （F=41.160， P

Introduction: Chronic insomnia disorder (CID) significantly impacts well-being and daily functioning. Daridorexant, a double orexin receptor blocker, has shown efficacy in randomized clinical trials and has been recently approved for the treatment of CID in adult patients. This retrospective observational study aimed to describe real-world data on daridorexant effectiveness and safety in adult patients with CID. Methods: Consecutive patients initiating on-label daridorexant at the Sleep Medicine Centre, University Hospital of Rome Tor Vergata were enrolled. Baseline and 30-day follow-up (FU) evaluations included patients' and CID characteristics, comorbidities, and clinicians' and patients' subjective ratings of changes with the Clinical and Patient Global Impression-Improvement scores (CGI-Is and PGI-Is), as well as Insomnia Severity Index (ISI) scores in a subgroup of patients. Results: Sixty-nine patients initiated 50-mg daily dosage. At FU, 58% of both patients and clinicians rated CID as improved on CGI-Is and PGI-Is, with no differences based on comorbidities, sex, or number of previous medications. No significant predictors of CGI-Is and PGI-Is improvement were identified. At FU, ISI scores (n = 24) significantly decreased from 18.25 ± 3.21 to 12.08 ± 6.12 (Z = 8.000; p < 0.001). Of these, eight patients (33.3%) had absence of insomnia symptoms, and no patients reported a worsening in ISI score categories. Conclusions: This study suggests daridorexant to be effective and safe in real-world CID treatment whether used as a first-ever treatment, switch, or add-on, as reflected by subjective and objective measures and the absence of serious treatment-related adverse events. Future research on larger cohorts should explore daridorexant potential across diverse patient characteristics. [ABSTRACT FROM AUTHOR]

BackgroundChronic Insomnia Disorder (CID) is highly prevalent among older adults and impairs cognitive function. Insomnia accelerates the progression of mild cognitive impairment (MCI) and increases the risk of developing dementia. Acupuncture has been demonstrated in improving sleep quality and cognitive function. This study aims to explore the functional brain characteristics of CID with MCI patients and to assess the effects of acupuncture therapy using functional near-infrared spectroscopy (fNIRS).Methods and designThis study is a single-center randomized controlled trial. Participants will be randomly assigned to the manual acupuncture group or the placebo acupuncture group for an 8-week intervention period. fNIRS data will be collected during resting test and working memory test at baseline and at end of the intervention. The primary outcome is the change of the Montreal Cognitive Assessment (MoCA) score, secondary outcomes include the change of Mini-Mental State Examination (MMSE), Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and Apathy Evaluation Scale-Informant (AES-I).DiscussionThe results of the study will provide insights into the effects of acupuncture on sleep quality and cognitive performance in CID with MCI patients. By utilizing fNIRS technology, we will elucidate the neural functional characteristic underlying the therapeutic benefits of acupuncture.Clinical trial registrationhttps://ClinicalTrials.gov, identifier ChiCTR2300076182.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been increasingly used as a treatment modality for chronic insomnia disorder (CID). However, our understanding of the mechanisms underlying the efficacy of rTMS is limited.ObjectiveThis study aimed to investigate rTMS-induced alterations in resting-state functional connectivity and to find potential connectivity biomarkers for predicting and tracking clinical outcomes after rTMS.MethodsThirty-seven patients with CID received a 10-session low frequency rTMS treatment applied to the right dorsolateral prefrontal cortex. Before and after treatment, the patients underwent resting-state electroencephalography recordings and a sleep quality assessment using the Pittsburgh Sleep Quality Index (PSQI).ResultsAfter treatment, rTMS significantly increased the connectivity of 34 connectomes in the lower alpha frequency band (8-10 Hz). Additionally, alterations in functional connectivity between the left insula and the left inferior eye junction, as well as between the left insula and medial prefrontal cortex, were associated with a decrease in PSQI score. Further, the correlation between the functional connectivity and PSQI persisted 1 month after the completion of rTMS as evidenced by subsequent electroencephalography (EEG) recordings and the PSQI assessment.ConclusionBased on these results, we established a link between alterations in functional connectivity and clinical outcomes of rTMS, which suggested that EEG-derived functional connectivity changes were associated with clinical improvement of rTMS in treating CID. These findings provide preliminary evidence that rTMS may improve insomnia symptoms by modifying functional connectivity, which can be used to inform prospective clinical trials and potentially for treatment optimization.

Abstract Background Cognitive behavioral therapy for insomnia (CBT-I) is among the recommended non-pharmacological treatments for patients with insomnia. While there are multiple reports on the effects of CBT-I treatment, few studies evaluating the factors associated with the treatment response to CBT-I have been reported. The present study aimed to confirm the effects of CBT-I in patients with insomnia and to examine the clinico-demographic factors that can predict the outcomes of CBT-I in these patients. Methods Overall, 62 patients were included in the present study. To confirm the effectiveness of CBT-I, we compared the pre- and post-CBT-I therapy values of several sleep parameters. Furthermore, to identify the clinico-demographic factors that could be predictive of the treatment response to CBT-I, we performed generalized linear model (GLM) analysis. Results The values of several sleep parameters were significantly lower after treatment than at baseline. The results of the GLM analysis revealed that sex and occupation were significantly associated with the treatment response to CBT-I. Conclusions The present results suggest that several clinico-demographic factors should be considered in the treatment of patients with insomnia.

Abstract Background Primary care physicians often lack resources and training to correctly diagnose and manage chronic insomnia disorder. Tools supporting chronic insomnia diagnosis and management could fill this critical gap. A survey was conducted to understand insomnia disorder diagnosis and treatment practices among primary care physicians, and to evaluate a diagnosis and treatment algorithm on its use, to identify ways to optimize it specifically for these providers. Methods A panel of experts developed an algorithm for diagnosing and treating chronic insomnia disorder, based on current guidelines and experience in clinical practice. An online survey was conducted with primary care physicians from France, Germany, Italy, Spain, and the United Kingdom, who treat chronic insomnia patients, between January and February 2023. A sub-sample of participants provided open-ended feedback on the algorithm and gave suggestions for improvements. Results Overall, 106 primary care physicians completed the survey. Half (52%, 55/106) reported they did not regularly screen for insomnia and half (51%, 54/106) felt they did not have enough time to address patients’ needs in relation to insomnia or trouble sleeping. The majority (87%,92/106) agreed the algorithm would help diagnose chronic insomnia patients and 82% (87/106) agreed the algorithm would help improve their clinical practice in relation to managing chronic insomnia. Suggestions for improvements were making the algorithm easier to read and use. Conclusion The algorithm developed for, and tested by, primary care physicians to diagnose and treat chronic insomnia disorder may offer significant benefits to providers and their patients through ensuring standardization of insomnia diagnosis and management.

Background: Cognitive behavioral therapy for insomnia (CBT-I) is among the recommended non-pharmacological treatments for patients with insomnia. While there are multiple reports on the effects of CBT-I treatment, few studies evaluating the factors associated with the treatment response to CBT-I have been reported. The present study aimed to confirm the effects of CBT-I in patients with insomnia and to examine the clinico-demographic factors that can predict the outcomes of CBT-I in these patients. Methods: Overall, 62 patients were included in the present study. To confirm the effectiveness of CBT-I, we compared the pre- and post-CBT-I therapy values of several sleep parameters. Furthermore, to identify the clinico-demographic factors that could be predictive of the treatment response to CBT-I, we performed generalized linear model (GLM) analysis. Results: The values of several sleep parameters were significantly lower after treatment than at baseline. The results of the GLM analysis revealed that sex and occupation were significantly associated with the treatment response to CBT-I. Conclusions: The present results suggest that several clinico-demographic factors should be considered in the treatment of patients with insomnia. [ABSTRACT FROM AUTHOR]

Rumination, a common factor of chronic insomnia disorder (CID) caused by cognitive-emotional arousal, is associated with an increased amount of rapid eye movement (REM) sleep. However, the specific subtypes, such as phasic REM and tonic REM, that contribute to the increased REM sleep have not been reported. This study aimed to determine the association between rumination and different REM sleep subtypes in patients with CID. This study enrolled 35 patients with CID and 27 age- and sex-matched healthy controls. The Immersion-Rumination Questionnaire evaluated participants' rumination, and the Insomnia Severity Index was used to assess insomnia severity. Finally, polysomnography was used to monitor objective sleep quality and quantification of different types of REM. The CID patients had higher rumination scores than the healthy controls. They had a shorter REM sleep duration, less phasic REM, a lower percentage of phasic REM time, and a higher percentage of tonic REM time. Spectral analysis revealed that the patients affected by insomnia had higher β power during REM sleep, higher β and σ power during phasic REM sleep, and higher β, and γ power during tonic REM sleep. Partial correlation analysis showed that rumination in the CID patients correlated negatively with the duration of phasic REM sleep. Additionally, rumination correlated negatively with δ power in REM sleep and positively with β power in REM sleep, tonic REM sleep, phasic REM sleep, N3and N2 sleep in the patients with CID. The CID patients had stronger rumination, reduced total and phasic REM sleep, and the stronger rumination was, the shorter phasic REM was and the higher fast (β) wave power in REM sleep. • To evaluate the features of phasic and tonic rapid eye movement sleep and rumination in chronic insomnia disorder patients. • The more intense rumination in chronic insomnia patients, the shorter their phasic REM sleep. • Research on phasic and tonic REM could help us better understand insomnia and mood disorders. [ABSTRACT FROM AUTHOR]

To explore the relationship between nocturnal levels of stress-related hormones and different sleep-wake states in chronic insomnia disorder (CID) patients. Thirty-three CID patients and 34 good sleepers were enrolled and completed assessment of sleep log, Pittsburgh Sleep Quality Index and Insomnia Severity Index. During a-overnight polysomnography monitoring, the patients' vein bleeds were continually collected at different time points (pre-sleep, deep-sleep, 5-min or 30-min waking, and morning waking-up). The control subjects' bleeds were collected only at 22:00 and morning waking-up. The serum hormones were detected using enzyme-linked immunosorbent assay. Compared with at pre-sleep, the level of cortisol was significantly higher at morning waking-up respectively in two-group subjects (Ps < 0.001), with insignificant inter-group differences in cortisol, corticotropin releasing hormone and copeptin at the two time-points. In the patients, the nocturnal secretion curves of three hormones were similar, with the highest concentration at morning waking-up, followed by 30-min waking, 5-min waking, pre-sleep, and deep-sleep. The patients' cortisol (Z = 79.192, P < 0.001) and copeptin (Z = 12.333, P = 0.015) levels were statistically different at different time-points, with higher cortisol at morning waking-up relative to deep-sleep, pre-sleep and 5-min waking (Ps < 0.05), and at 30-min waking relative to deep-sleep and pre-sleep (Ps < 0.05), and higher copeptin at morning waking-up relative to deep-sleep (P < 0.05). In CID, the nocturnal wakes were instantaneously accompanied by high level, and deep sleep was accompanied by the lowest levels, of stress-related hormones, especially in cortisol, supporting the insomniac hypothesis of increased nocturnal pulse-release of cortisol. [Display omitted] • The blood was collected according to sleep or waking states obtained with real-time monitor of overnight polysomnography in the chronic insomniacs. • 2.In both insomniac and good sleep subjects, the level of cortisol at morning waking-up was significantly higher than that at pre-sleep. • The levels of stress-related hormones (CRH, cortisol, and copeptin) varied with different states of sleep-waking during night. • Obviously, the level of cortisol was the lowest at deep sleep and the highest at long-time waking during sleep. • Our findings support the hypothesis of increased pulse-release of nocturnal cortisol under the insomniac condition. [ABSTRACT FROM AUTHOR]

Appraise the evidence for daridorexant 50 mg and 25 mg versus placebo when treating chronic insomnia disorder in terms of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH). NNT, NNH, and LHH were calculated from a 3-month pivotal Phase 3 study (N = 930; randomized 1:1:1 to daridorexant 50 mg, daridorexant 25 mg, or placebo once nightly). Wakefulness after sleep onset, latency to persistent sleep, self-reported total sleep time, Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), and Insomnia Severity Index were used for the NNT efficacy analysis. NNH safety analysis was performed using rates of adverse events (AEs) occurring in >1% of the participants in any arm. LHH was assessed for all NNT estimates, contrasting them with NNH estimates for somnolence, headache, and fatigue AEs. NNT estimates for daridorexant 50 mg versus placebo were <10 for clinically meaningful thresholds across all outcomes. NNT estimates for daridorexant 25 mg versus placebo were not as robust as those observed for daridorexant 50 mg, with many values exceeding 10. NNH estimates for daridorexant 50 mg and 25 mg versus placebo did not show a statistically significant treatment difference except for falls, where NNH was negative for the daridorexant 50 mg group (−44 [95% CI −328; −21]; rate of falls was greater with placebo than for daridorexant 50 mg). All LHH ratios at Months 1 and 3 were >1 (except for daridorexant 25 mg for the IDSIQ alert/cognition domain), indicating that patients were more likely to respond to daridorexant 50 mg and 25 mg than to experience an AE of somnolence, headache, or fatigue. Daridorexant 50 mg and 25 mg have a favorable benefit–risk ratio over 3 months. Daridorexant 50 mg demonstrated more robust (lower) NNT estimates versus placebo than daridorexant 25 mg. Daridorexant, a dual orexin receptor antagonist, is a new treatment for chronic insomnia disorder. This analysis examined the effect and safety of daridorexant 50 and 25 mg, using data from a 3-month Phase 3 study (NCT03545191) to measure 'number needed to treat' (NNT) and 'number needed to harm' (NNH). NNT estimates how many patients need to be treated over a specific period to see one more beneficial response. Estimates versus placebo <10 indicate an effective treatment. Daridorexant 50 mg estimates were <10 for all objective and subjective measurements of insomnia assessed in this analysis, including evaluation of daytime functioning. NNT estimates for daridorexant 25 mg versus placebo were not as robust as daridorexant 50 mg, with values >10. NNH is calculated in the same way as NNT but estimates harmful outcomes rather than benefits. Estimates versus placebo >10 means the treatment is reasonably well tolerated. Using NNT and NNH, the 'likelihood to be helped or harmed' (LHH) ratio was calculated, determining how more likely a patient is to benefit versus experiencing harm from a treatment (LHH of >1 denotes a positive benefit–risk ratio). Both daridorexant doses had a favorable benefit–risk ratio over 3 months with LHH > 1. This analysis supports daridorexant 50 mg as the optimal dose to treat insomnia in adults, offering improved effectiveness compared with daridorexant 25 mg, with a similarly good safety profile. [ABSTRACT FROM AUTHOR]

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Background: Primary care physicians often lack resources and training to correctly diagnose and manage chronic insomnia disorder. Tools supporting chronic insomnia diagnosis and management could fill this critical gap. A survey was conducted to understand insomnia disorder diagnosis and treatment practices among primary care physicians, and to evaluate a diagnosis and treatment algorithm on its use, to identify ways to optimize it specifically for these providers. Methods: A panel of experts developed an algorithm for diagnosing and treating chronic insomnia disorder, based on current guidelines and experience in clinical practice. An online survey was conducted with primary care physicians from France, Germany, Italy, Spain, and the United Kingdom, who treat chronic insomnia patients, between January and February 2023. A sub-sample of participants provided open-ended feedback on the algorithm and gave suggestions for improvements. Results: Overall, 106 primary care physicians completed the survey. Half (52%, 55/106) reported they did not regularly screen for insomnia and half (51%, 54/106) felt they did not have enough time to address patients' needs in relation to insomnia or trouble sleeping. The majority (87%,92/106) agreed the algorithm would help diagnose chronic insomnia patients and 82% (87/106) agreed the algorithm would help improve their clinical practice in relation to managing chronic insomnia. Suggestions for improvements were making the algorithm easier to read and use. Conclusion: The algorithm developed for, and tested by, primary care physicians to diagnose and treat chronic insomnia disorder may offer significant benefits to providers and their patients through ensuring standardization of insomnia diagnosis and management. [ABSTRACT FROM AUTHOR]

The hypothalamus is a well-established core structure in the sleep-wake cycle. While previous studies have not consistently found whole hypothalamus volume changes in chronic insomnia disorder (CID), differences may exist at the smaller substructural level of the hypothalamic nuclei. The study aimed to investigate the differences in total and subfield hypothalamic volumes, between CID patients and healthy controls (HCs) in vivo, through an advanced deep learning-based automated segmentation tool. A total of 150 patients with CID and 155 demographically matched HCs underwent T1-weighted structural magnetic resonance scanning. We utilized FreeSurfer v7.2 for automated segmentation of the hypothalamus and its five nuclei. Additionally, correlation and causal mediation analyses were performed to investigate the association between hypothalamic volume changes, insomnia symptom severity, and hypothalamus-pituitary-adrenal (HPA) axis-related blood biomarkers. CID patients exhibited larger volumes in the right anterior inferior, left anterior superior, and left posterior subunits of the hypothalamus compared to HCs. Moreover, we observed a positive association between blood corticotropin-releasing hormone (CRH) levels and insomnia severity, with anterior inferior hypothalamus (a-iHyp) hypertrophy mediating this relationship. In conclusion, we found significant volume increases in several hypothalamic subfield regions in CID patients, highlighting the central role of the HPA axis in the pathophysiology of insomnia. • Patients with CID exhibited enlarged volumes in several hypothalamic subfield regions. • Insomnia severity positively correlated with both elevated blood CRH levels and a-iHyp volume hypertrophy. • Causal mediation analysis revealed that a-iHyp hypertrophy mediated the relationship between CRH level and insomnia severity. [ABSTRACT FROM AUTHOR]

Objective: Insomnia disorder stands out as one of the prevalent clinical sleep and psychiatric disorders. Prior research has unequivocally demonstrated variations in the diversity and abundance of gut microbiota among individuals with insomnia disorder. These alterations may play a direct or indirect role in the onset and progression of insomnia disorder by compromising the integrity of the intestinal barrier. This study aims to evaluate the impairment of the intestinal barrier in individuals with insomnia disorder by scrutinizing the serum functionality of this barrier. Materials and methods: 45 patients with chronic insomnia disorder and 30 matched healthy volunteers were meticulously selected based on inclusion criteria. ELISA technology was employed to measure serum levels of diamine oxidase (DAO), D-lactic acid (D-LA), intestinal fatty acid binding protein (I-FABP), and endothelin (ET). Spearman correlation analysis was used to explore the relationship between intestinal mucosal markers and clinical characteristics. Data were analyzed using SPSS 26.0. Results: Compared to the healthy control group, the insomnia disorder group exhibited significantly elevated scores on subjective mood and sleep scales (GAD-7, PHQ-9, HAMA, HAMD, PSQI, and ISI) (P < 0.05). Overnight PSG indicated a notable increase in bed time, total wake time, sleep onset latency, and wake after sleep onset in individuals with insomnia disorder. Additionally, there was a decrease in sleep efficiency and alterations in sleep structure (increased proportion of N1 and N3 stages, prolonged N1 stage) (P < 0.05). The chronic insomnia disorder group displayed significantly reduced concentrations of serum DAO, D-LA, I-FABP, and ET (P < 0.05). Furthermore, significant positive correlations were identified between intestinal epithelial barrier markers and sleep efficiency, while negative correlations were found with wake after sleep onset, total wake time, PSQI, HAMA, and HAMD. Additionally, D-LA levels were significantly positively correlated with ET concentrations. Conclusion: Individuals with chronic insomnia disorder manifest disruptions in sleep structure, heightened susceptibility to anxiety and depressive moods, and impaired intestinal barrier function. These findings suggest that the occurrence and development of insomnia disorder may be linked to the impairment of the intestinal barrier. [ABSTRACT FROM AUTHOR]

The importance of the suprachiasmatic nucleus (SCN, also called the master circadian clock) in regulating sleep and wakefulness has been confirmed by multiple animal research. However, human studies of SCN in vivo are still nascent. Recently, the development of resting-state functional magnetic resonance imaging (fMRI) has made it possible to study SCN-related connectivity changes in patients with chronic insomnia disorder (CID). Hence, this study aimed to explore whether sleep–wake circuitry (i.e., communication between the SCN and other brain regions) is disrupted in human insomnia. Forty-two patients with CID and 37 healthy controls (HCs) underwent fMRI scanning. Resting-state functional connectivity (rsFC) and Granger causality analysis (GCA) were performed to find abnormal functional and causal connectivity of the SCN in CID patients. In addition, correlation analyses were conducted to detect associations between features of disrupted connectivity and clinical symptoms. Compared to HCs, CID patients showed enhanced rsFC of the SCN-left dorsolateral prefrontal cortex (DLPFC), as well as reduced rsFC of the SCN-bilateral medial prefrontal cortex (MPFC); these altered cortical regions belong to the "top-down" circuit. Moreover, CID patients exhibited disrupted functional and causal connectivity between the SCN and the locus coeruleus (LC) and the raphe nucleus (RN); these altered subcortical regions constitute the "bottom-up" pathway. Importantly, the decreased causal connectivity from the LC-to-SCN was associated with the duration of disease in CID patients. These findings suggest that the disruption of the SCN-centered "top-down" cognitive process and "bottom-up" wake-promoting pathway may be intimately tied to the neuropathology of CID. [ABSTRACT FROM AUTHOR]

This study used event-related potential (ERP) and resting-state functional connectivity (rs-FC) approaches to investigate the neural mechanisms underlying the emotional attention bias in patients with chronic insomnia disorder (CID). Twenty-five patients with CID and thirty-three demographically matched healthy controls (HCs) completed clinical questionnaires and underwent electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) scans. EEG analysis examined the group differences in terms of reaction times, P3 amplitudes, event-related spectral perturbations, and inter-trial phase synchrony. Subsequently, seed-based rs-FC analysis of the amygdala nuclei (including the central-medial amygdala [CMA] and basolateral amygdala [BLA]) was performed. The relationship between P3 amplitude, rs-FC and clinical symptom severity in patients with CID was further investigated by correlation analysis. CID patients exhibited shorter reaction times than HCs in both standard and deviant stimuli, with the abnormalities becoming more pronounced as attention allocation increased. Compared to HCs, ERP analysis revealed increased P3 amplitude, theta wave power, and inter-trial synchrony in CID patients. The rs-FC analysis showed increased connectivity of the BLA-occipital pole, CMA-precuneus, and CMA-angular gyrus and decreased connectivity of the CMA-thalamus in CID patients. Notably, correlation analysis of the EEG and fMRI measurements showed a significant positive correlation between the P3 amplitude and the rs-FC of the CMA-PCU. This study confirms an emotional attention bias in CID, specifically in the neural mechanisms of attention processing that vary depending on the allocation of attentional resources. Abnormal connectivity in the emotion-cognition networks may constitute the neural basis of the abnormal scalp activation pattern. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the neural mechanisms underlying working memory impairment in patients with chronic insomnia disorder (CID) using event-related potentials (ERP) and resting-state functional connectivity (rsFC) approaches. Participants, including CID patients and healthy controls (HCs), completed clinical scales and underwent electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). EEG analysis compared reaction times, P3 amplitudes, event-related spectral perturbations (ERSP), and inter-trial phase synchronisation (ITPS) between CID patients and HCs. Subsequently, frontal regions (i.e., the Superior Frontal Gyrus [SFG] and Middle Frontal Gyrus [MFG]) corresponding to the EEG were selected as seeds for rsFC analysis. Correlation analyses were conducted to further investigate the relationship between functional connectivity abnormalities in brain regions and clinical symptom severity and P3 amplitude in CID patients. Compared to HCs, CID patients exhibited slower reaction times across all working memory conditions, with the deficits becoming more pronounced as memory load increased. ERP analysis revealed increased P3 amplitude, theta wave power, and reduced inter-trial synchrony in CID patients. rsFC analysis showed decreased connectivity of SFG-posterior cingulated cortex (PCC), SFG-MFG, and MFG-frontal pole (FP), and increased connectivity of MFG- Middle Temporal Gyrus (MTG)in CID patients. Importantly, a significant correlation was found between the rsFC of SFG-MTG and P3 amplitude during 1-back. This study confirms deficits in working memory capacity in patients with CID, specifically in the neural mechanisms of cognitive processing that vary depending on the level of cognitive load. Alterations in connectivity patterns within and between the frontal and temporal regions may be the neural basis of the cognitive impairment. • Patients with CID exhibited working memory deficits and altered cognitive load management. • Alterations in connectivity patterns within and between the frontal and temporal regions may underlie working memory deficits. • The integration of ERP and fMRI explored the potential mechanisms of working memory deficitsfrom a multimodal perspective. [ABSTRACT FROM AUTHOR]

BackgroundChronic insomnia disorder (CID) is increasing in prevalence year by year, is long lasting, and potentially risky. Acupuncture has been widely used in the clinical management of this condition. However, there is still a lack of direct evidence on the dose-effect relationship between different acupuncture courses and clinical efficacy. To identify this relationship, we will design a randomized controlled trial to clarify the difference in efficacy of different acupuncture courses for CID.Methods and designThis is a prospective, parallel, single center randomized controlled trial. Two hundred and one participants with CID will be randomly divided into three groups (Group A, Group B, and Group C). The three groups will be given acupuncture therapy for 4, 6, and 8 weeks, three sessions per week, with at least 1 day between sessions. Follow-up will continue until the third month after the end of treatment. The primary outcome is the Insomnia Severity Index (ISI), and secondary outcomes include percentage of ISI

Objectives: Insulin-like growth factor 1 (IGF-1) is a crucial neurotrophin that is produced in the brain and periphery and may play an important role in insomnia and mood disorders. We aimed to analyze its serum concentrations in patients with chronic insomnia disorder (CID). Methods: Patients with CID were enrolled in this study and divided into the CID group [Generalized Anxiety Disorder-7 (GAD-7) score < 10] and the CID with anxiety group (GAD-7 score ≥ 10). Age-and sex-matched healthy volunteers were recruited as controls. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality and the GAD-7 and the Patient Health Questionnaire-9 to assess emotional status. All subjects were monitored via polysomnography, and the serum IGF-1 concentrations in their peripheral blood were detected via enzyme-linked immunosorbent assays. Results: We enrolled 65 patients with CID (of whom 35 had anxiety) and 36 controls. The PSQI score and IGF-1 concentration in the CID and CID with anxiety groups were higher than those in the control group. The apparent difference in IGF-1 concentration between the CID and CID with anxiety groups was not statistically significant. The IGF-1 concentration in patients with CID was linearly correlated with the GAD-7 score, PSQI score, and stage 3 non-rapid eye movement (stage N3) time. Conclusion: The serum IGF-1 concentration in patients with CID was lower than that of participants without CID, negatively correlated with anxiety score and sleep quality, and positively correlated with stage N3 time. [ABSTRACT FROM AUTHOR]

Background Repetitive transcranial magnetic stimulation (rTMS) has been increasingly used as a treatment modality for chronic insomnia disorder (CID). However, our understanding of the mechanisms underlying the efficacy of rTMS is limited. Objective This study aimed to investigate rTMS-induced alterations in resting-state functional connectivity and to find potential connectivity biomarkers for predicting and tracking clinical outcomes after rTMS. Methods Thirty-seven patients with CID received a 10-session low frequency rTMS treatment applied to the right dorsolateral prefrontal cortex. Before and after treatment, the patients underwent resting-state electroencephalography recordings and a sleep quality assessment using the Pittsburgh Sleep Quality Index (PSQI). Results After treatment, rTMS significantly increased the connectivity of 34 connectomes in the lower alpha frequency band (8-10 Hz). Additionally, alterations in functional connectivity between the left insula and the left inferior eye junction, as well as between the left insula and medial prefrontal cortex, were associated with a decrease in PSQI score. Further, the correlation between the functional connectivity and PSQI persisted 1 month after the completion of rTMS as evidenced by subsequent electroencephalography (EEG) recordings and the PSQI assessment. Conclusion Based on these results, we established a link between alterations in functional connectivity and clinical outcomes of rTMS, which suggested that EEG-derived functional connectivity changes were associated with clinical improvement of rTMS in treating CID. These findings provide preliminary evidence that rTMS may improve insomnia symptoms by modifying functional connectivity, which can be used to inform prospective clinical trials and potentially for treatment optimization. [ABSTRACT FROM AUTHOR]

Chronic insomnia disorder is one of the most common problems in postmenopausal women, exacerbated by underdiagnosis and improper treatment. This double-blinded, randomized, placebo-controlled trial was conducted to evaluate the potential of vitamin E to treat chronic insomnia as an alternative to sedative drugs and hormonal therapy. The study enrolled 160 postmenopausal women with chronic insomnia disorder, divided randomly into two groups. The vitamin E group received 400 units of mixed tocopherol daily, while the placebo group received an identical oral capsule. The primary outcome of this study was sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI), a self-evaluated and standardized questionnaire. The secondary outcome was the percentage of participants using sedative drugs. There were no significant differences in baseline characteristics between the study groups. However, the median PSQI score at baseline was slightly higher in the vitamin E group compared with the placebo (13 (6, 20) vs. 11 (6, 20); p-value 0.019). After one month of intervention, the PSQI score was significantly lower (indicating better sleep quality) in the vitamin E group compared with the placebo (6 (1, 18) vs. 9 (1, 19); p-value 0.012). Moreover, the improvement score was significantly higher in the vitamin E group compared with the placebo (5 (−6, 14) vs. 1 (−5,13); p-value < 0.001). In addition, there was a significant reduction in the percentage of patients using sedative drugs in the vitamin E group (15%; p-value 0.009), while this reduction was not statistically significant in the placebo group (7.5%; p-value 0.077). This study demonstrates vitamin E's potential as an excellent alternative treatment for chronic insomnia disorder that improves sleep quality and reduces sedative drug use. [ABSTRACT FROM AUTHOR]

Chunlong Li,1 Yuexia Liu,2 Ning Yang,3 Zhihong Lan,4 Shumei Huang,3 Yunfan Wu,3 Xiaofen Ma,3 Guihua Jiang3 1Department of Medical Imaging, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’ s Republic of China; 2Department of Ultrasound, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’ s Republic of China; 3Department of Medical Imaging, Guangdong Second Provincial General Hospital, Guangzhou, People’s Republic of China; 4Department of Medical Imaging, Zhuhai City People’s Hospital, Zhuhai, People’s Republic of ChinaCorrespondence: Guihua Jiang; Xiaofen Ma, Email GH.jiang2002@163.com; xiaofenma12@163.comIntroduction: In recent years, people have gained a profound understanding of chronic insomnia disorder (CID), but the pathophysiological mechanism of CID is still unclear. There is some evidence that the locus coeruleus (LC) is involved in the regulation of wakefulness in CID, but there have been few studies using brain functional imaging. The purpose of this study was to evaluate the resting-state functional connectivity (FC) between the LC and other brain voxels in CID and whether these abnormal FC are involved in the regulation of wakefulness.Methods: A total of 49 patients with chronic insomnia disorder and 47 healthy controls (HC) matched for gender, age, and education were examined with rs-fMRI in this study. The LC was selected as the region of interest, and then seed-based analysis was conducted on the LC and other voxels to obtain the brain regions with abnormal FC. The correlation between the FC value of the abnormal connection area and the clinical scale score was analyzed.Results: Compared with the HC, the FC between the LC and right precuneus, right posterior cingulate cortex, left middle temporal gyrus, left calcarine, and right superior orbitofrontal cortex was significantly enhanced (p < 0.05, FDR correction), and the functional connectivity signal value between the locus coeruleus and left middle temporal gyrus was positively correlated with the Self-Rating Depression Scale (p = 0.021).Conclusion: The abnormal FC between the LC and multiple brain regions may contribute to a better understanding of the neurobiological mechanism of CID.Keywords: chronic insomnia disorder, default mode network, functional connectivity, locus coeruleus, seed-based analysis

Abstract Background The objective of this study was to explore the stigma and related influencing factors in individuals with chronic insomnia disorder (CID). Methods A total of 70 CID patients and 70 healthy controls (CON) were enrolled in the study. All subjects completed the assessments of sleep, emotion, and cognition. Their stigma and life quality were measured using the Chronic Stigma Scale and the 36-Item Short-Form Health Survey (SF-36). Results The ratio of individuals with stigma was significantly different between CID and CON groups (C2 = 35.6, p

The ascending arousal system plays a crucial role in individuals' consciousness. Recently, advanced functional magnetic resonance imaging (fMRI) has made it possible to investigate the ascending arousal network (AAN) in vivo. However, the role of AAN in the neuropathology of human insomnia remains unclear. Our study aimed to explore alterations in AAN and its connections with cortical networks in chronic insomnia disorder (CID). Resting‐state fMRI data were acquired from 60 patients with CID and 60 good sleeper controls (GSCs). Changes in the brain's functional connectivity (FC) between the AAN and eight cortical networks were detected in patients with CID and GSCs. Multivariate pattern analysis (MVPA) was employed to differentiate CID patients from GSCs and predict clinical symptoms in patients with CID. Finally, these MVPA findings were further verified using an external data set (32 patients with CID and 33 GSCs). Compared to GSCs, patients with CID exhibited increased FC within the AAN, as well as increased FC between the AAN and default mode, cerebellar, sensorimotor, and dorsal attention networks. These AAN‐related FC patterns and the MVPA classification model could be used to differentiate CID patients from GSCs with 88% accuracy in the first cohort and 77% accuracy in the validation cohort. Moreover, the MVPA prediction models could separately predict insomnia (data set 1, R2 =.34; data set 2, R2 =.15) and anxiety symptoms (data set 1, R2 =.35; data set 2, R2 =.34) in the two independent cohorts of patients. Our findings indicated that AAN contributed to the neurobiological mechanism of insomnia and highlighted that fMRI‐based markers and machine learning techniques might facilitate the evaluation of insomnia and its comorbid mental symptoms. [ABSTRACT FROM AUTHOR]

Purpose: Insomnia is one of the most common diseases in elderly patients, which seriously affect the quality of life and psychological state of patients. The purpose of this study was to investigate the changes in the functional network pattern of the prefrontal cortex in patients with chronic insomnia disorder (CID) after taking drugs, using non-invasive and low-cost functional neuroimaging with multi-channel near-infrared spectroscopy (fNIRS). Methods: All subjects were assessed using the Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and fNIRS. The fNIRS assessment consists of two parts: the verbal fluency test (VFT) task state and the resting state, which assessed the differences in prefrontal activation and functional connectivity, respectively. Results: A total of 30 patients with chronic insomnia disorder (CID) and 15 healthy peers completed the study. During the VFT task, a significantly lower PFC activation was observed in patients with insomnia compared to the control group (P < 0.05). However, the PFC activation in patients taking medication was higher than in patients who did not receive medication. Functional connectivity analysis showed a weaker mean PFC channel connectivity strength in patients with CID who did not receive drug treatment. Drug treatment resulted in enhanced functional connectivity of the prefrontal lobe, especially the DLPFC and frontal poles. Conclusion: A weak prefrontal cortex response was detected in patients with CID when performing the VFT task, which could be enhanced by taking hypnotics. The weakened right prefrontal lobe network may play a role in the development of CID. fNIRS may serve as a potential tool to assess sleep status and guide drug therapy. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare the effectiveness of the only Food and Drug Administration-authorized prescription digital therapeutic (PDT) Somryst* versus cognitive behavioral therapy for insomnia (CBT-I), or FDA-approved prescription medications for insomnia.Methods: A systematic literature review was undertaken to identify relevant studies. A Bayesian network meta-analysis (NMA) was conducted to examine (1) mean change in insomnia severity index (ISI); (2) proportional change in ISI remitters; (3) mean change in wake after sleep onset (WASO); and (4) mean change in sleep onset latency (SOL).Results: Twenty studies provided data on the PDT, CBT-I, CBT-I in combination with self-help (SH), or two prescription medications (eszopiclone and zolpidem). The PDT was associated with significant mean change in ISI (-5.77, 95% Credible Interval [CI] -8.53, -3.07) and ISI remitters (OR 12.33; 95% CI 2.28, 155.91) compared to placebo, and had the highest probability of being the most effective treatment overall for ISI mean change (56%), and ISI remitters (64%). All evaluated interventions significantly outperformed placebo for WASO but no significant differences were observed for SOL (five interventions). Sensitivity analyses excluding medications and meta-regression (assessing type, duration, delivery method for CBT-I) did not affect NMA results.Conclusions: This network meta-analysis demonstrated that a PDT delivering CBT-I had the highest probability of being most effective compared to face-to-face CBT-I, prescription sleep medications, or placebo, as measured by reductions in mean ISI score from baseline and ISI-determined remittance.* Somryst is the registered trademark for a prescription digital therapeutics for insomnia developed by Pear Therapeutics (US), Inc. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to explore the stigma and related influencing factors in individuals with chronic insomnia disorder (CID). Methods: A total of 70 CID patients and 70 healthy controls (CON) were enrolled in the study. All subjects completed the assessments of sleep, emotion, and cognition. Their stigma and life quality were measured using the Chronic Stigma Scale and the 36-Item Short-Form Health Survey (SF-36). Results: The ratio of individuals with stigma was significantly different between CID and CON groups (C2 = 35.6, p < 0.001). Compared with the CON group, the CID group had higher scores for total stigma (U = 662.0, p < 0.001), internalized stigma (U = 593.0, p < 0.001), enacted stigma (U = 1568.0, p < 0.001), PSQI (U = 2485.0, p < 0.001) and HAMD-17 (U = 69.5, p < 0.001) as well as lower scores for MoCA-C (U = 3997.5, p < 0.001) and most items of SF-36. Partial correlation analysis showed that different items of the Chronic Stigma Scale were positively correlated with illness duration, PSQI and HAMD-17 scores, while negatively correlated with one or more items of the SF-36. Multivariate regression analysis showed that illness duration and the Mental Health domain of the SF-36 were independent risk factors for one or more items of stigma in CID patients. Conclusion: Patients with CID have an increased risk of stigma. Moreover, illness duration and Mental Health may be primary factors related to stigma. [ABSTRACT FROM AUTHOR]

Background: Chronic insomnia disorder (CID) is a highly prevalent sleep disorder, which influences people's daily life and is even life threatening. However, whether the restingstate regional homogeneity (ReHo) of disrupted brain regions in CID can be reshaped to normal after treatment remains unclear. Methods: A novel intervention real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) was used to train 28 CID patients to regulate the activity of the left amygdala for three sessions in 6 weeks. The ReHo methodology was adopted to explore its role on resting-state fMRI data, which were collected before and after training. Moreover, the relationships between changes of clinical variables and ReHo value of altered regions were determined. Results: Results showed that the bilateral dorsal medial pre-frontal cortex, supplementary motor area (SMA), and left dorsal lateral pre-frontal cortex had decreased ReHo values, whereas the bilateral cerebellum anterior lobe (CAL) had increased ReHo values after training. Some clinical scores markedly decreased, including Pittsburgh Sleep Quality Index, Insomnia Severity Index, Beck Depression Inventory, and Hamilton Anxiety Scale (HAMA). Additionally, the ReHo values of the left CAL were positively correlated with the change in the Hamilton depression scale score, and a remarkable positive correlation was found between the ReHo values of the right SMA and the HAMA score. Conclusion: Our study provided an objective evidence that amygdala-based rtfMRINF training could reshape abnormal ReHo and improve sleep in patients with CID. The improved ReHo in CID provides insights into the neurobiological mechanism for the effectiveness of this intervention. However, larger double-blinded sham-controlled trials are needed to confirm our results from this initial study. [ABSTRACT FROM AUTHOR]

The purpose of the study was to systematically investigate the structural and functional abnormalities in the subregions of the thalamus and to examine their clinical relevance in patients with short-term and chronic insomnia disorder (ID). Thirty-four patients with short-term ID, 41 patients with chronic ID, and 46 healthy controls (HCs) were recruited. Grey matter volume and seed-based resting-state functional connectivity (RSFC) were compared for each thalamic subregion (bilateral cTtha, lPFtha, mPFtha, mPMtha, Otha, Pptha, rTtha, and Stha) between the three groups. Spearman's correlation was used to estimate the associations between thalamic alterations and clinical variables. Compared with the HCs and chronic ID group, the short-term ID group exhibited lower RSFC of the left cTtha, lPFtha, Otha and Pptha with the bilateral caudate. In addition, the short-term ID group exhibited lower RSFC between the left mPFtha and left caudate in comparison with the other two groups. Convergent RSFC alterations were found in the left cTtha and Otha with the right parahippocampal gyrus in both ID groups. Moreover, a positive correlation was found for the left Otha–caudate RSFC with the Epworth sleepiness scale scores (r = 0.340, P = 0.040). Our findings suggest shared and unique RSFC alterations of certain thalamic subregions with paralimbic regions between short-term and chronic ID. These findings have implications for understanding common and specific pathophysiology of different types of ID. [ABSTRACT FROM AUTHOR]

Background: Epidemiological and observational clinical studies have found that insomnia is a risk factor for stroke and that, accordingly, insomnia is likely to cause changes of stroke-related biomarkers. There is substantial evidence that stroke is closely related to endothelial dysfunction and hypertension. The aim of this study is to investigate whether there is alteration of endothelial dysfunction (CD62E+) and hypertension (angiotensin II and copeptin) biomarkers in patients with chronic insomnia disorder (CID).Methods: The CID patients (N = 54) and the good sleepers (GS, N = 32) were enrolled. Pittsburgh sleep quality index (PSQI), pre-sleep arousal scale (PSAS) and polysomnography were used to assess their sleep and neuropsychological function. Serum levels of CD62E+, angiotensin II and copeptin were determined using a quantitative sandwich ELISA.Results: The CID group had higher serum levels of CD62E+, angiotensin II, and copeptin than the GS group. After controlling for sex, age, depression and apnea-hypopnea index, the partial correlation analysis revealed that the levels of CD62E+ and copeptin correlated positively with the PSAS score and negatively with the objective sleep quality. Angiotensin II levels negatively correlated with objective sleep onset latency. Moreover, there was a positive correlation between CD62E+ and angiotensin II. Principal components analysis revealed that CD62E+ and copeptin had a substantial correlation with parameters of subjective and objective sleep.Conclusion: Patients with CID exhibit endothelial activation, over-activated renin-angiotensin system and increased sympathetic excitability, as indicated by increased serum levels of CD62E+, angiotensin II and copeptin, with linking to poor sleep quality. [ABSTRACT FROM AUTHOR]

Study Objectives: This study aimed to investigate the alterations in resting-state electroencephalography (EEG) global brain connectivity (GBC) in patients with chronic insomnia disorder (CID) and to explore the correlation between macroscale connectomic variances and microscale neurotransmitter distributions., Methods: We acquired 64-channel EEG from 35 female CID patients and 34 healthy females. EEG signals were source-localized using individual brain anatomy and orthogonalized to mitigate volume conduction. Correlation coefficients between band-limited source-space power envelopes of the DK 68 atlas were computed and averaged across regions to determine specific GBC values. A support vector machine (SVM) classifier utilizing GBC features was employed to differentiate CID patients from controls. We further used Neurosynth and a 3D atlas of neurotransmitter receptors/transporters to assess the cognitive functions and neurotransmitter landscape associated with CID cortical abnormality maps, respectively., Results: CID patients exhibited elevated GBC within the medial prefrontal cortex and limbic cortex, particularly at the gamma carrier frequency, compared to controls (pFDR < .05). GBC patterns were found to effectively distinguish CID patients from controls with a precision of 90.8% in the SVM model. The cortical abnormality maps were significantly correlated with meta-analytic terms like "cognitive control" and "emotion regulation." Notably, GBC patterns were associated with neurotransmitter profiles (pspin < .05), with neurotransmitter systems such as norepinephrine, dopamine, and serotonin making significant contributions., Conclusions: This work characterizes the EEG connectomic profile of CID, facilitating the cost-effective clinical translation of EEG-derived markers. Additionally, the linkage between GBC patterns and neurotransmitter distribution offers promising avenues for developing targeted treatment strategies for CID., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To observe the efficacy of acupuncture for reducing the south to reinforce the north on executive function, sleep structure and sleep quality in patients with chronic insomnia disorder of heart-kidney disharmony., Methods: A total of 100 patients with chronic insomnia disorder of heart-kidney disharmony were randomized into an acupuncture group (50 cases, 1 case dropped out) and a western medication group (50 cases, 2 cases dropped out). Acupuncture for reducing the south to reinforce the north was applied at Baihui (GV 20) and bilateral Shenmen (HT 7), Sanyinjiao (SP 6), Shenmai (BL 62), Zhaohai (KI 6), Xinshu (BL 15), Shenshu (BL 23) in the acupuncture group, once a day, 5 days a week. Lorazepam tablet was given orally in the western medication group, 0.5-1 mg a time, once a day. Both groups were treated for 4 weeks. The Stroop color-word test (SCWT) indexes (the time consuming and the correct number of card A, B, C and the Stroop interference effect [SIE]), sleep structure indexes (total sleep time [TST], sleep latency [SL], wake after sleep onset [WASO], sleep efficiency [SE], non-rapid eye movement period 1 [N1], non-rapid eye movement period 2 [N2], non-rapid eye movement period 3 [N3], rapid eye movement period [REM]) and Pittsburgh sleep quality index (PSQI) score were observed before and after treatment in the two groups., Results: After treatment, the time consuming of card B and C, the time consuming and the correct number of SIE, SL, WASO, N1, N2, as well as the sub-item scores and total score of PSQI were decreased ( P <0.05, P <0.01), the correct number of card A, B and C, TST, SE, N3 and REM were increased ( P <0.01) compared with those before treatment in the acupuncture group; the time consuming of card C and SIE, the correct number of card A and SIE, TST, SE, REM were increased ( P <0.05, P <0.01), SL, WASO, N1, as well as the sub-item scores of sleep quality, sleep latency, sleep duration, sleep efficiency, daytime function and total score of PSQI were decreased ( P <0.01) compared with those before treatment in the western medication group. After treatment, in the acupuncture group, the time consuming of card C, the time consuming and the correct number of SIE, N1, N2, as well as the sub-item scores of sleep quality, sleep dysfunction, daytime function and total score of PSQI were lower than those in the western medication group ( P <0.01), the correct number of card B and C, N3, REM were higher than those in the western medication group ( P <0.01)., Conclusions: Acupuncture for reducing the south to reinforce the north can improve the executive function of patients with chronic insomnia disorder of heart-kidney disharmony, adjust the sleep structure, and improve the night sleep quality and daytime body function.

Study Objectives: Chronic insomnia disorder (CID) is a prevalent sleep disorder that frequently cooccurs with anxiety. The association between insomnia and anxiety has been established; however, the neurobiological basis of this relationship remains unclear. This study aimed to investigate the neural markers of CID patients with and without anxiety and to determine whether specific neural connectivity mediates the relationship between insomnia and anxiety., Methods: This study included 180 participants, comprising CID patients with anxiety (CID-A), CID patients without anxiety (CID-NA), and good sleep controls. All participants completed self-reported measures of sleep quality and anxiety severity and underwent functional magnetic resonance imaging. Brain functional integration was measured using functional connectivity density (FCD) and resting-state functional connectivity (rsFC). Correlation and mediation analyses were used to examine the relationships among brain connectivity, sleep quality, and anxiety severity., Results: The CID-NA and CID-A groups showed decreased local FCD in the medial prefrontal cortex (mPFC) and disrupted rsFC between the precuneus and other brain regions. Only the CID-A group exhibited altered long-range FCD in the precuneus and the rsFC between the anterior default mode network (DMN, e.g. mPFC) and posterior DMN (e.g. precuneus). Mediation analysis revealed DMN dysconnectivity underlying the association between poor sleep quality and anxiety symptoms., Conclusions: This study identified shared and distinct brain circuit disruptions in the CID-NA and CID-A groups, with deficits in DMN connectivity as a potential neural mechanism through which disrupted sleep augments anxiety. These findings may facilitate the development of personalized therapies for insomnia and associated anxiety problems., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Sleep is instrumental in safeguarding emotional well-being. While the susceptibility to both insomnia and anxiety has been demonstrated to involve intricate brain systems, the neuroimaging profile of chronic insomnia disorder with comorbid anxiety symptoms (CID-A) remains unexplored. Employing machine learning methodologies, this study aims to elucidate the distinct neural substrates underlying CID-A and to investigate whether these cerebral markers can prognosticate anxiety symptoms in patients with insomnia., Methods: Functional magnetic resonance imaging (fMRI) data were procured from a relatively large cohort (dataset 1) comprised of 47 CID-A patients, 49 CID patients without anxiety (CID-NA), and 48 good sleeper controls (GSC). Aberrant cerebral functional alterations were assessed through functional connectivity strength (FCS) and resting-state functional connectivity (rsFC). Subsequently, Support Vector Regression (SVR) models were constructed to predict anxiety symptoms in CID patients based on neuroimaging features, which were validated utilizing an external cohort (dataset 2)., Results: In comparison to CID-NA and GSC subjects, CID-A patients exhibited heightened FCS in the right dorsomedial prefrontal cortex (DMPFC), a central hub within the negative affective network. Moreover, the SVR models revealed that DMPFC-related rsFC/FCS features could be employed to predict anxiety symptoms in two independent cohorts of CID patients., Limitation: Modifications in brain functionality might vary across insomnia subtypes., Conclusion: The present findings suggest a potential negative affective network model for the neuropathophysiology of CID accompanied by anxiety. Importantly, the negative affective network pattern may serve as a predictor for anxiety symptoms in CID patients., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Study Objectives: This study investigated alterations in resting-state functional connectivity (RSFC) and hyperarousal biomarkers in patients with chronic insomnia disorder (CID), compared with good sleepers (GS). We also examined the relationships between altered RSFC and hyperarousal biomarkers., Methods: Fifty patients with CID and 52 GS completed self-reporting questionnaires, and then underwent polysomnography and resting-state functional magnetic resonance imaging. We analyzed RSFC in the amygdala (AMG) and anterior insula (aINS), which are core regions of the salience network that are likely to be involved in hyperarousal. We also analyzed electroencephalography (EEG) relative beta power and heart rate variability (HRV) parameters (e.g. low and high frequency) during sleep. We then tested between-group differences in the RSFC and hyperarousal biomarkers; we examined correlations of RSFC with EEG beta power and HRV., Results: Compared with GS, patients with CID showed more negative RSFC between the right amygdala (R.AMG) and left supramarginal gyrus (L.SMG), but less positive RSFC between the left aINS and bilateral lateral prefrontal cortex. The R.AMG-L.SMG RSFC was negatively correlated with EEG beta power in central regions (C3: r = -0.336, p = 0.012; C4: r = -0.314, p = 0.024)., Conclusions: Decreased RSFC between the R.AMG and L.SMG in patients with insomnia may reflect the difficulty in cortical top-down regulation of the AMG, indicating daytime hyperarousal. Individuals who experience hyperarousal during the daytime may also exhibit cortical hyperarousal during sleep, as indicated by increased EEG beta power., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)