Sleep advances : a journal of the Sleep Research Society最新文献

Study objectives: To examine whether there is a temporal association between sleep disturbance and multimorbidity.

Methods: We performed a cross-sectional and longitudinal observational analysis in people aged 40 years or more, recruited from the knee pain and related health in the community cohort study. The primary exposure was the Sleep Problems Index II score in tertiles measured at baseline. The primary outcome was count of chronic conditions developed in 5 years. Pain, low mood, and anxiety were measured at 2 years as mediators. Poisson regression was used to calculate adjusted relative risk and 95% confidence intervals.

Results: We included 4488 participants in the cross-sectional analysis at baseline and 1941 in the 5-year longitudinal analysis. At baseline, the adjusted relative risks for prevalent multimorbidity were 1 (reference) for tertile 1, 1.09 (95% confidence interval; 1.01-1.18) for tertile 2, and 1.21 (95% confidence interval; 1.11-1.32) for tertile 3 of the sleep disturbance score (p for trend <.001). Of the total association between sleep disturbance and multimorbidity, 14 per cent (95% confidence interval; 9% to 19%) were mediated by pain and 7 per cent (95% confidence interval; 2% to 13%) by low mood. In the 5 year follow-up, the adjusted relative risk for incident multimorbidity were 1 (reference) for tertile 1, 1.12 (95% confidence interval; 0.98-1.28) for tertile 2, and 1.25 (95% confidence interval; 1.06-1.47) for tertile 3 (p for trend .007). Of the total association between sleep disturbance and multimorbidity, 10 per cent (95% confidence interval; 2% to 18%) was mediated by pain.

Conclusions: Sleep disturbance is associated with multimorbidity. The association is dose-dependent, temporal, and partially mediated by pain.

Study objectives: Diverse studies have reported longer sleep durations and later circadian timing during the initial COVID-19 lockdown period. Little is known about whether effects persisted after 2020. This analysis addresses three questions: (1) How did sleep timing and duration change from 2017 to 2023? (2) Did working from home explain trends? (3) Did effects differ by education, income, or race/ethnicity groups?

Methods: The American Time Use Survey is a nationally representative survey conducted by the US Bureau of Labor Statistics that collects 24-hour time diaries. These data are used to identify respondents who worked on the sampled day, their work location (home or not), and three sleep variables: wake-up time, bedtime, and 24-hour sleep total. Ordinary least squares regression is used to answer the study questions, comparing the COVID time period (May 2020 to December 2023) to PRECOVID (January 2017 to March 2020).

Results: Sleep duration was longer in the COVID time period compared to PRECOVID, by 0.23 hours (95% confidence interval = 0.17, 0.29), with earlier average bedtimes and later average waking times. There were no significant secular trends in sleep outcomes within the COVID time period, suggesting that these changes have continued through 2023. Controlling for working from home modestly attenuated, but did not eliminate, the COVID effects. Effects were generally similar across sociodemographic groups.

Conclusions: COVID-related changes in sleep for working adults in the United States, specifically later circadian timing and increased duration, seem to be sustained through 2023.

Study objectives: Two in five Veterans report symptoms of insomnia, with higher rates among those who drink heavily. Although Cognitive Behavioral Therapy for Insomnia (CBT-I) has demonstrated efficacy among those with Alcohol Use Disorder, abstinence is often considered a prerequisite for treatment, leaving its impact unclear among those who are actively drinking. This trial tested the efficacy of CBT-I among heavy-drinking Veterans with insomnia (#NCT03804788).

Methods: Veterans from across the United States were randomly assigned to CBT-I or sleep hygiene control. Participants completed retrospective surveys and 14 sleep diaries at baseline, post-treatment, and 3-month follow-up. Primary outcomes were feasibility and insomnia severity. All other outcomes are secondary/exploratory. Intent-to-treat analyses were conducted using multilevel models.

Results: Recruitment spanned June 2019 to March 2023 (N = 71, 80% male, M = 38 years). On average, we recruited 4 participants per month, with retention of 86% at post-treatment and 90% at follow-up. Of 38 CBT-I participants, 33 (87%) completed all 5 treatment sessions, and most responded to treatment (based on change in outcome scores; 22/38 at post, 27/38 at follow-up). Relative to control (n = 33), CBT-I participants reported large improvements in insomnia severity, both post-treatment [d = 1.26 (95% CI: 0.74, 1.76)] and at 3-month follow-up [d = 1.33 (95% CI: 0.81, 1.84)]. At follow-up, results for use of alcohol as a sleep aid [d = 0.66 (95% CI: 0.18, 1.14)] and sleep medication [d = 0.44 (95% CI: -0.03, 0.91)] also favored CBT-I.

Conclusions: CBT-I is feasible among heavy-drinking Veterans and has large effects on insomnia severity. Studies testing mechanistic effects on alcohol outcomes are warranted.

Clinical trial information: The iTAP Study for Veterans, registered on clinicaltrials.gov (#NCT03804788) on January 11, 2019: https://clinicaltrials.gov/study/NCT03804788?term=NCT03804788&rank=1.

Study objectives: There is a higher risk of cardiovascular disease (CVD) in patients with obstructive sleep apnea (OSA) and innate immunity is a potential pathophysiologic pathway. The objective of this study was to determine whether nocturnal hypoxemia is associated with circulating markers of innate immunity in OSA.

Methods: This was a cross-sectional study of an observational cohort from the multicentre, clinic-based, Canadian Sleep and Circadian Network. Oxygen desaturation index 4% (ODI4%) was used to diagnose and determine the severity of OSA. The percentage of time spent below SpO₂ <90% (T90) and minimum SpO₂ we considered as other measures of nocturnal hypoxemia. Multiple linear regressions were used to assess associations between total white blood cell (WBC) and subsets and ODI and hypoxemia indices.

Results: A total of 1296 patients were included in the analysis. There was a positive association between ODI4% and lymphocyte count, adjusting for confounders. For every 1-SD increase in ODI4%, lymphocyte counts increased by 0.08 × 10⁹ L (95% CI 0.01 to 0.15) SD. Patients with severe OSA (ODI4% ≥ 30 events/hour) had significantly higher total WBC and lymphocyte count than non-OSA cohort, in the adjusted model, p-value <.02, for both. There was a positive association between T90 and total WBC, neutrophil, lymphocyte, and monocyte count, adjusting for confounders. Minimum SpO₂ was independently associated with total WBC, neutrophil, and monocyte counts.

Conclusions: In this pan-Canadian clinic-based cohort of individuals with suspected OSA, nocturnal hypoxemia indices were associated with an increase in total WBC and subset counts.

Study objectives: Trazodone is an antidepressant with robust hypnotic effects, frequently prescribed off-label to treat insomnia. Trazodone has gained recent attention in the context of neurodegenerative diseases because sleep has been proposed as a novel target for disease-modifying therapeutics. Preclinical research in rodents examining the effects of trazodone on sleep is limited, so here we aimed to develop a translationally focused protocol to study the sleep-promoting effects of trazodone in mice.

Methods: We investigated the effects of voluntary oral trazodone administration at doses of 10, 40, and 60 mg/kg on sleep in C57BL/6J mice (n = 15; females = 6; age 10-13 months). Mice were dosed with trazodone for 6 consecutive nights, while being recorded with intracranially implanted 2-channel electroencephalogram (EEG) and electromyography (EMG). EEG/EMG recordings were analyzed for time spent in each vigilance state and power spectra.

Results: A single dose of trazodone, administered prior to the onset of the 12-h rest phase, dose-dependently increased non-rapid eye movement (NREM) sleep and delta power during NREM sleep, at the expense of rapid eye movement (REM) sleep. These effects on sleep persisted after six consecutive days of dosing, albeit to a lesser extent.

Conclusions: We have validated a novel voluntary oral administration protocol for trazodone use in mice and have shown that trazodone effectively promotes NREM in mice. Our novel protocol will be useful for future research investigating the effects of trazodone on sleep in mouse models of disease.

The function of rapid eye movement (REM) sleep in consolidating emotional memories and reducing emotional charge has been studied, but evidence remains conflicting. Our study employed the targeted memory reactivation (TMR) technique, which posits that specific sleep memories can be reactivated through sensory stimuli during sleep. Additionally, the late positive potential (LPP), a component of event-related brain potentials, was measured while participants (N = 16, 22.5 ± 1.2 years) viewed negative, neutral, or positive images (old images) paired with an odor stimulus. During subsequent REM sleep, the same odor was presented in the TMR condition, while an odorless stimulus was presented in the control condition. Upon awakening, participants performed the same task as before sleep, with new images added to test memory. The results demonstrated that TMR increased the LPP amplitude between 500 and 800 ms after image onset following sleep for negative old images; however, no changes were observed in the LPP in the same range for negative new images and neutral or positive images. TMR during REM sleep did not influence performance on the memory task, nor did it affect levels of arousal or emotional valence immediately after viewing the emotional images. These preliminary findings from our pilot study suggest that either the presentation of phenylethyl alcohol itself or the reprocessing induced by TMR during REM sleep selectively enhances the LPP in emotional processing of previously encountered negative stimuli. Due to the small sample size of this study, further investigation is warranted to evaluate the robustness of the results.

In a dynamic process that ultimately affords memories their persistence, memory reconsolidation can serve to strengthen associations following reactivation, particularly in sleep, where active processes may effect overnight enhancement. Reactivation can also occur in wake, where improvement would be unexpected. In an earlier study using performance on the Weather Prediction Task (WPT) as a measure of probabilistic category learning, we looked at the effect of sleep and found significant improvement after a daytime nap, where improvement correlated with the amount of REM sleep obtained. When we introduced interference training following sleep, this REM sleep benefit vanished: post-learning task memory was otherwise preserved. Here, we follow up on these results and test whether reactivation itself-wake reactivation-might be sufficient to induce the improvement found after REM sleep. Our results show that it is not: we saw no improvement on the WPT following reactivation in wake, suggesting sleep may be unique in supporting memory improvement. When we looked at interference effects, we saw unexplained differences between wake and sleep that suggest that while interference is uniformly destabilizing of WPT memories during wake, interference after REM show effects on the memory trace formed during initial learning that are distinctly different from its effects on the subsequently sleep-enhanced memory.

This paper is a review of my life as a sleep researcher and clinician. I chanced into sleep by being at the right place at the right time. Over the last 45 years, I became an expert on sleep and circadian rhythms in aging, in Alzheimer's disease and Parkinson's disease and in cancer. We were one of the first to show how common sleep apnea and periodic limb movements in sleep are in the elderly. We "moved" into the nursing home and showed how disrupted sleep is in these patients. We used light therapy to improve sleep in the nursing home. We studied the effect of CPAP on sleep and cognition in both Alzheimer's disease and Parkinson's disease. And we were some of the first to study sleep and circadian rhythms in women with breast cancer, starting the evaluations before they started their chemotherapy. These studies were both observational and treatment studies. I am very proud of the work we did. For me, everything revolves around sleep. And that is the beginning of my story.

Analyzing scored sleep is a fundamental prerequisite to understanding how sleep changes between health and disease. Classically, this is accomplished by manually calculating various measures (e.g. percent of non-rapid eye movement sleep) from a collection of scored sleep files. This process can be tedious and error-prone, especially when studies include large animal numbers or involve long recording sessions. To address this issue, we present SleepInvestigatoR, a versatile tool that can quickly organize and analyze multiple scored sleep files into a single output. The function is written in the open-source statistical language R and has a total of 25 parameters that can be set to match a wide variety of experimental needs. SleepInvestigatoR delivers a total of 23 unique measures of sleep, including all measures commonly reported in the rodent literature. A simple plotting function is also provided to quickly graph and visualize the scored data. All code is designed to be implemented with little formal coding knowledge, and step-by-step instructions are provided on the corresponding GitHub page. Overall, SleepInvestigatoR provides the sleep researcher a critical tool to increase efficiency, interpretation, and reproducibility in analyzing scored rodent sleep.

Study objectives: Chronotype, a manifestation of circadian rhythms, affects morning or evening preferences and ease of getting up. This study explores the genetic basis of morning chronotype and ease of getting up, focusing on the G-protein-coupled receptor locus, GPR61.

Methods: We analyzed the genetic correlation between chronotype and ease of getting up using linkage disequilibrium score regression with summary statistics from the UK Biobank (n = 453,379). We prioritized shared signals between chronotype and ease of getting up using the Human Genetic Evidence (HuGE) score. We assessed the significance of GPR61 and the lead variant rs12044778 through co-localization and in silico analyses from ENCODE, Genotype-Tissue Expression, Hi-C, and Knockout Mouse Project databases to explore potential regulatory roles of causal genes.

Results: We identified a strong genetic correlation (Rg = 0.80, p = 4.9 × 10³²⁴) between chronotype and ease of getting up. Twenty-three genes, including three circadian core clock components, had high HuGE scores for both traits. Lead variant rs12044778 in GPR61 was prioritized for its high HuGE score (45) and causal pleiotropy (posterior probability = 0.98). This morningness variant influenced gene expression in key tissues: decreasing GPR61 in tibial nerve, increasing AMIGO1 in subcutaneous adipose, and increasing ATXN7L2 in the cerebellum. Functional knockout models showed GPR61 knockout increased fat mass and activity, AMIGO1 knockout increased activity, and ATXN7L2 knockout reduced body weight without affecting activity.

Conclusions: Our findings reveal pleiotropic genetic factors influencing chronotype and ease of getting up, emphasizing GPR61's rs12044778 and nearby genes like AMIGO1 and ATXN7L2. These insights advance our understanding of circadian preferences and suggest potential therapeutic interventions.