Journal of Sleep Research最新文献

GAD67 impacts insomnia as a key enzyme catalysing the conversion of glutamate (Glu) to gamma-aminobutyric acid (GABA). Senegenin enhances neuroprotection and is used widely to treat insomnia and other neurological diseases. This study aimed to investigate how senegenin regulates insomnia through a GAD67-mediated signalling pathway. We measured GAD67 expression levels in insomnia patients and evaluated the expression levels of GAD67 and Keap1/Nrf2/Parkin/PINK1-related cytokines following GAD67 lentiviral transfection in PC12 cells and in rat models. We also assessed cellular reactive oxygen species (ROS) and mitochondrial membrane potential levels. Additionally, EEG/EMG was used to analyse the sleep phases of rats and to assess memory and exploration functions. Pathological changes and the expression of GAD67 and sleep-related proteins in the hippocampus were examined. The results showed that GAD67 expression was increased in insomnia patients, ROS levels were elevated, and the mitochondrial membrane potential was decreased in the GAD67-KD group. Insomnia rats exhibited changes in sleep rhythm, learning, and exploration dysfunction, pathological changes in the CA1 region of the hippocampus, and differential expression of GAD67 and sleep-related factors. Inhibitory neurofactor expression levels were decreased in insomnia rats, showing a positive correlation in the GAD67-KD group and a negative correlation in the GAD67-OE group. Conversely, excitatory factor expression levels were increased in insomnia rats, showing a positive correlation in the GAD67-KD group and a negative correlation in the GAD67-OE group. Senegenin intervention modulated cytokine expression levels. In conclusion, GAD67 negatively regulates insomnia, and senegenin can regulate insomnia by mediating the expression of cytokines in the GAD67-regulated Keap1/Nrf2/Parkin/PINK1 pathway.

Obstructive sleep apnea (OSA) syndrome commonly leads to excessive daytime sleepiness (EDS). Pitolisant, a selective histamine-3 receptor antagonist, is efficacious at doses up to 20 mg once daily in OSA treated or not with continuous positive airway pressure (CPAP). We assessed the efficacy and safety of pitolisant at doses up to 40 mg once daily in patients with moderate to severe OSA treated or not with CPAP therapy. In this phase 3, multicentre, randomised, double-blind, placebo-controlled clinical trial, patients with OSA were assigned 2:1 to receive pitolisant (according to an individual up-titration scheme, 10, 20 or 40 mg once daily) or placebo for 12 weeks. The primary endpoint was a change in the Epworth Sleepiness Scale (ESS) score from baseline to week 12. Secondary endpoints included a change in reaction time using the Oxford Sleep Resistance test (OSleR), Clinical Global Impression of Change (CGI-C), and Patient's Global Opinion of the Effect (PGOE) of study treatment. Overall, 361 patients (mean age 52.4 years, 77.3% male; mean apnea-hypopnea index [AHI] 27.0 events/h) were randomised to receive pitolisant (n = 242; 50% received CPAP) or placebo (n = 119; 48.7% CPAP). After the dose-adjustment phase (week 3), 88.8% of patients received pitolisant 40 mg. Compared with placebo, pitolisant produced a significant reduction in the ESS score at week 12 (least square mean difference -2.6 (95% CI: -3.4; -1.8; p < 0.001)) irrespective of CPAP use; and improved the reaction time on OSleR, CGI-C, and PGOE at week 12. Pitolisant was well tolerated; no new safety signals were identified. In conclusion, pitolisant up to 40 mg once daily was an effective treatment for EDS in patients with moderate to severe OSA irrespective of CPAP use.

Insomnia symptoms represent a significant public health concern, as it engenders substantial long-term health consequences. Considerable research has established the detrimental impacts of child maltreatment on sleep problems among university students. However, the role of self-efficacy in the association between childhood maltreatment and insomnia remains unclear. This study aimed to examine the associations between child maltreatment and insomnia symptoms among university students, and to investigate whether self-efficacy moderated the effects of child maltreatment on insomnia symptoms. A total of 2014 participants with random cluster sampling method were recruited from Jinan University in Guangzhou, China, from October 2022 to November 2022. Adjusting for covariates, the results of multiple logistic regression indicated that the participants with the experience of any type of child maltreatment (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.63-3.07), childhood emotional abuse (OR 2.58, 95% CI 1.95-3.41), childhood emotional neglect (OR 1.16, 95% CI 0.87-1.54), childhood physical abuse (OR 2.15, 95% CI 1.60-2.8), childhood physical neglect (OR 2.19, 95% CI 1.64-2.92), childhood sexual abuse (OR 1.98, 95% CI 1.46-2.68) were more likely to report insomnia symptoms than those without. Individuals reporting one-two types and three-five types of child maltreatment were 1.81 times (95% CI 1.30-2.52) and 3.77 times (95% CI 2.58-5.50) more likely to report insomnia symptoms than those reporting zero types of child maltreatment, respectively. Furthermore, robust linear regression analysis revealed that self-efficacy moderated the associations between child maltreatment and insomnia symptoms (β = 0.007, 95% CI 0.004-0.010). These findings underscore the need for integrated mental health education, support services, and faculty training to address the impact of child maltreatment on insomnia symptoms among university students. Policy recommendations include advocating for comprehensive mental health services, incorporating self-efficacy initiatives, and fostering community engagement for a holistic approach to student well-being.

Although there have been promising findings for smartphone application (app)-delivered cognitive behavioural therapy for insomnia (CBT-I), previous trials have not screened participants rigorously for insomnia disorder and used therapist support. Based on the above, we aimed to examine the effects of smartphone app-delivered CBT-I with telephone support against a waitlist (WL) in a sample with insomnia disorder. A total of 64 participants with insomnia disorder were randomised to smartphone app-delivered CBT-I (n = 32) or a WL (n = 32). Smartphone app-delivered CBT-I consisted of six weekly smartphone app modules with 15 min of telephone support per week. At pre- and post-treatment, and the 3-month follow-up, we assessed insomnia symptoms and associated correlates and consequences. At post-treatment, we also assessed measures related to adherence (therapist support, exercise/module completion), self-rated perception of treatment content, activity, and adverse events. CBT-I significantly outperformed the WL with large effects on the primary outcome (d = 2.26) and was significantly different on most of the secondary outcomes with medium to large effects. CBT-I also resulted in a significantly larger proportion of treatment remitters (CBT-I: 64.5-77.4%, WL: 6.5-6.9%) and responders (CBT-I: 77.4-90.3%, WL: 19.4-24.1%) at post-treatment and follow-up, compared to the WL. Treatment was associated with high satisfaction, high adherence, low attrition, and few treatment-impeding adverse events. Based on the medium to large effects of smartphone app-delivered CBT-I with telephone support, this trial highlights the potential of delivering CBT-I exclusively through an app with therapist telephone support for high efficacy, satisfaction, and adherence.

Dreaming, a common yet mysterious cognitive phenomenon, is an involuntary process experienced by individuals during sleep. Although the fascination with dreams dates back to ancient times and gained therapeutic significance through psychoanalysis in the early twentieth century, its scientific investigation only gained momentum with the discovery of rapid eye movement (REM) sleep in the 1950s. This review synthesises current research on the neurobiological and psychological aspects of dreaming, including factors influencing dream recall and content, neurophysiological correlates, and experimental models, and discusses the implications for clinical practice.

Sleep is vital for health. It has regenerative and protective functions. Its disruption reduces the quality of life and increases susceptibility to disease. During sleep, there is a cyclicity of distinct phases that are studied for clinical purposes using polysomnography (PSG), a costly and technically demanding method that compromises the quality of natural sleep. The search for simpler devices for recording biological signals at home addresses some of these issues. We have reworked a single-channel in-ear electroencephalography (EEG) sensor grounded to a commercially available memory foam earplug with conductive tape. A total of 14 healthy volunteers underwent a full night of simultaneous PSG, in-ear EEG and actigraphy recordings. We analysed the performance of the methods in terms of sleep metrics and staging. In another group of 14 patients evaluated for sleep-related pathologies, PSG and in-ear EEG were recorded simultaneously, the latter in two different configurations (with and without a contralateral reference on the scalp). In both groups, the in-ear EEG sensor showed a strong correlation, agreement and reliability with the 'gold standard' of PSG and thus supported accurate sleep classification, which is not feasible with actigraphy. Single-channel in-ear EEG offers compelling prospects for simplifying sleep parameterisation in both healthy individuals and clinical patients and paves the way for reliable assessments in a broader range of clinical situations, namely by integrating Level 3 polysomnography devices. In addition, addressing the recognised overestimation of the apnea-hypopnea index, due to the lack of an EEG signal, and the sparse information on sleep metrics could prove fundamental for optimised clinical decision making.

Circadian disruption, arising from conflict between internal circadian time and behavioural sleep-wake and fasting-feeding rhythms, may contribute to the prevalence of type 2 diabetes mellitus and disease severity. Previous studies have demonstrated a link between irregular breakfast eating and poorer metabolic health. We aimed to further explore the relationships between breakfast habits, circadian misalignment (social jetlag), and metabolic parameters in a cohort of adult participants with type 2 diabetes mellitus. A total of 330 adult participants with type 2 diabetes mellitus attending for routine clinical review completed structured questionnaires to assess habitual sleep timing, chronotype, and social jetlag. Statistical analysis was via inferential groupwise approaches and path analysis to establish interdependencies of effects of social jetlag, chronotype, and breakfast eating regularity on HbA1c. 22.7% of the participants reported eating breakfast five times or fewer a week, and were categorised as irregular breakfast eaters. Compared with those who ate breakfast six or seven times a week, irregular breakfast eaters had significantly higher HbA1c and diastolic blood pressure, were younger and had greater social jetlag. In the path analysis, irregular breakfast eating exerted a direct effect on HbA1c, whilst social jetlag exerted only an indirect effect on HbA1c through breakfast eating regularity. Chronotype did not exert any effect on HbA1c, but did exert an indirect effect on breakfast eating regularity via social jetlag. Our results showed that adult participants with type 2 diabetes mellitus, who ate breakfast irregularly had poorer metabolic health and greater social jetlag. The relationship between social jetlag and glycaemic control appears to be mediated through breakfast eating habits.

While sleep disturbances are prevalent in older people and are linked with poor health and cognitive outcomes, screening for the range of sleep disturbances is inefficient and therefore not ideal nor routine in memory and cognition clinic settings. We aimed to develop and validate a new brief self-report questionnaire for easy use within memory and cognition clinics. The design for this study was cross-sectional. Older adults (aged ≥50 in Sydney, Australia) were recruited from a memory and cognition research clinic. Participants (N = 402, mean age 67.3 years, range 50-86, 63.6% female) completed a comprehensive medical, neuropsychological, and mental health assessment, alongside self-report instruments, including existing sleep questionnaires and a new 10-item sleep questionnaire, the CogSleep Screener. We examined the factor structure, convergent validity, internal consistency, and discriminant validity of this novel questionnaire. Using exploratory principal component analysis, a 3-factor solution was generated highlighting the factors of Insomnia, Rapid Eye Movement (REM) Symptoms and Daytime Sleepiness. Each factor was significantly correlated with currently used sleep questionnaires for each subdomain (all Spearman rho >0.3, all p < 0.001), suggesting good convergent validity. Internal consistency was also good (Cronbach's α = 0.73). Receiver operating characteristic curves showed good discriminative ability between participants with and without sleep disturbances (all area under curve >0.7, all p < 0.01). The CogSleep Screener has good psychometric properties in older to elderly adults attending a memory and cognition clinic. The instrument has the potential to be used in memory clinics and other clinical settings to provide quick and accurate screening of sleep disturbances.

Obstructive sleep apnea (OSA) has been associated with incident type 2 diabetes mellitus (T2DM); however, few prospective epidemiological studies have accounted for important T2DM predictors including pre-diabetes status and testosterone. Participants in the longitudinal Men Androgens Inflammation Lifestyles Environment and Stress (MAILES) study, who underwent eight-channel home-based polysomnography (PSG) in 2010-2011 (n = 824) and were free of diabetes at baseline were included in the analysis (n = 682). From 2015 to 2021, 78.6% (n = 536) completed at least one follow-up assessment. Incident T2DM was determined by self-reported doctor diagnosis, diabetes medications, plasma glucose (fasting ≥7.0 mmol/L or random ≥11.0 mmol/L) or glycated haemoglobin ≥6.5%. Conservative hierarchical Poisson regression models adjusted associations of PSG metrics (categorical and continuous) for age, waist circumference, baseline fasting glucose and testosterone concentrations. In all, 52 men (9.7%) developed T2DM over a mean (range) of 8.3 (3.5-10.5) years. Significant age- and waist circumference-adjusted association of incident T2DM with rapid eye movement (REM) sleep apnea-hypopnea index (AHI) ≥20 events/h (incidence rate ratio [IRR] 1.5, 95% confidence interval [CI] 0.8-2.8; p = 0.23] and highest quartile of delta index (IRR 2.1, 95% CI 0.95-4.6; p = 0.066) were attenuated after adjustment for baseline glucose and testosterone, and the association with the lowest quartile of mean oxygen saturation persisted (IRR 4.2, 95% CI 1.7-10.3; p = 0.029). Categorical measures of AHI severity, oxygen desaturation index, and hypoxia burden index (HBI) were not independently associated with incident T2DM. Associations with T2DM were similar when continuous PSG variables were used; however, HBI was significant (IRR 1.015, 95% CI 1.006-1.024; p = 0.007). In a sub-sample with OSA treatment data (n = 479), these significant associations persisted after excluding adequately treated OSA (n = 32). Understanding underlying OSA endotypes generating hypoxaemia may identify opportunities for diabetes prevention.