Sleep and the gut microbiota in preschool aged children

Sleep plays a significant role in the mental and physical development of children. Emerging evidence in animals and human adults indicates a relationship between sleep and the gut microbiota; however, it is unclear whether the sleep of preschoolers during a key developmental period, associates with features of their gut microbiota. The objective of this study was to assess the relationship between sleep and gut microbiota in preschool aged children (4.37 ±0.48 years, n=143). Sleep measures included total nighttime sleep (TST), sleep efficiency (SE), and wake-time after sleep onset (WASO) assessed using actigraphy. Beta-diversity differences between children with low and high TST (p =0.048) suggest gut microbiota community differences. Particularly, relative abundance of Bifidobacterium was higher in the high TST group and Bacteroides, was higher in children who had higher SE and low WASO (LDA score >2). In contrast, some Lachnospiraceae members including Blautia and Coprococcus 1 were associated with shorter nighttime sleep duration and less efficiency, respectively. We also found a group of faecal metabolites, including specific neuroactive compounds and immunomodulating metabolites were associated with greater sleep efficiency and less time awake at night. Notably, tryptophan and its metabolizing products were higher in children who had higher SE or lower WASO (LDA score >2); concentration of propionate was higher in children with lower WASO (p =0.036). Overall, our results reveal a novel association between sleep and gut microbiota in preschool aged children. Longer nighttime sleep and greater sleep efficiency were associated with specific commensal bacteria that may regulate sleep through modulating neurotransmitter metabolism and the immune system.

Longitudinal associations between insomnia symptoms and all-cause mortality among middle-aged and older adults: A population-based cohort study

To date, there is no scientific consensus on whether insomnia symptoms increase mortality risk. We investigated longitudinal associations between time-varying insomnia symptoms (difficulty initiating sleep, difficulty maintaining sleep, early-morning awakening, and non-restorative sleep) and all-cause mortality among middle-aged and older adults during 14 years of follow-up. Data were obtained from 2004 through 2018 survey waves of the Health and Retirement Study in the United States for a population-representative sample of 15,511 respondents who were ≥50 years old in 2004. Respondents were interviewed biennially and followed through the end of the 2018 survey wave for the outcome. Marginal structural discrete-time survival analyses were employed to account for time-varying confounding and selection bias. Of the 15,511 cohort respondents (mean [±SD] age at baseline, 63.7 [±10.2] years; 56.0% females), 5,878 (31.9%) died during follow-up. At baseline (2004), 41.6% reported experiencing at least one insomnia symptom. Respondents who experienced one (HR=1.11; 95% CI: 1.03–1.20), two (HR=1.12; 95% CI: 1.01–1.23), three (HR=1.15; 95% CI: 1.05–1.27), or four (HR=1.32; 95% CI: 1.12–1.56) insomnia symptoms had on average a higher hazard of all-cause mortality, compared to those who were symptom-free. For each insomnia symptom, respondents who experienced difficulty initiating sleep (HR=1.12; 95% CI: 1.02–1.22), early-morning awakening (HR=1.09; 95% CI: 1.01–1.18), and nonrestorative sleep (HR=1.17; 95% CI: 1.09–1.26), had a higher hazard of all-cause mortality compared to those not experiencing the symptom. The findings demonstrate significant associations between insomnia symptoms and all-cause mortality, both on a cumulative scale and independently, except for difficulty maintaining sleep. Further research should investigate the underlying mechanisms linking insomnia symptoms and mortality.

Order matters: sleep spindles contribute to memory consolidation only when followed by rapid-eye-movement sleep

Sleep is known to benefit memory consolidation, but little is known about the contribution of sleep stages within the sleep cycle. The sequential hypothesis proposes that memories are first replayed during non-rapid-eye-movement (NREM or N) sleep and then integrated into existing networks during rapid-eye-movement (REM or R) sleep, two successive critical steps for memory consolidation. However, it lacks experimental evidence as N always precedes R sleep in physiological conditions. We tested this sequential hypothesis in patients with central hypersomnolence disorder, including patients with narcolepsy who present the unique, anti-physiological peculiarity of frequently falling asleep in R sleep before entering N sleep. Patients performed a visual perceptual learning task before and after daytime naps stopped after one sleep cycle, starting in N or R sleep and followed by the other stage (i.e. N-R vs. R-N sleep sequence). We compared over-nap changes in performance, reflecting memory consolidation, depending on the sleep sequence during the nap. Thirty-six patients who slept for a total of 67 naps were included in the analysis. Results show that sleep spindles are associated with memory consolidation only when N is followed by R sleep, that is in physiologically ordered N-R naps, thus providing support to the sequential hypothesis in humans. In addition, we found a negative effect of rapid-eye-movements in R sleep on perceptual consolidation, highlighting the complex role of sleep stages in the balance to remember and to forget.

Associations of sleep and circadian phenotypes with COVID-19 susceptibility and hospitalization: an observational cohort study based on the UK Biobank and a two-sample Mendelian randomization study

Study Objectives Sleep and circadian phenotypes are associated with several diseases. The present study aimed to investigate whether sleep and circadian phenotypes were causally linked with coronavirus disease 2019 (COVID-19)-related outcomes. Methods Habitual sleep duration, insomnia, excessive daytime sleepiness, daytime napping, and chronotype were selected as exposures. Key outcomes included positivity and hospitalization for COVID-19. In the observation cohort study, multivariable risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated. Two-sample Mendelian randomization (MR) analyses were conducted to estimate the causal effects of the significant findings in the observation analyses. Beta values and the corresponding 95% CIs were calculated and compared using the inverse variance weighting, weighted median, and MR-Egger methods. Results In the UK Biobank cohort study, both often excessive daytime sleepiness and sometimes daytime napping were associated with hospitalized COVID-19 (excessive daytime sleepiness [often vs. never]: RR=1.24, 95% CI=1.02-1.5; daytime napping [sometimes vs. never]: RR=1.12, 95% CI=1.02-1.22). In addition, sometimes daytime napping was also associated with an increased risk of COVID-19 susceptibility (sometimes vs. never: RR= 1.04, 95% CI=1.01-1.28). In the MR analyses, excessive daytime sleepiness was found to increase the risk of hospitalized COVID-19 (MR IVW method: OR = 4.53, 95% CI = 1.04-19.82), whereas little evidence supported a causal link between daytime napping and COVID-19 outcomes. Conclusions Observational and genetic evidence supports a potential causal link between excessive daytime sleepiness and an increased risk of COVID-19 hospitalization, suggesting that interventions targeting excessive daytime sleepiness symptoms might decrease severe COVID-19 rate.

Sleep and Circadian Informatics Data Harmonization: A Workshop Report from the Sleep Research Society and Sleep Research Network

The increasing availability and complexity of sleep and circadian data are equally exciting and challenging. The field is in constant technological development, generating better high-resolution physiological and molecular data than ever before. Yet, the promise of large-scale studies leveraging millions of patients is limited by suboptimal approaches for data sharing and interoperability. As a result, integration of valuable clinical and basic resources is problematic, preventing knowledge discovery and rapid translation of findings into clinical care. To understand the current data landscape in the sleep and circadian domains, the Sleep Research Society (SRS) and the Sleep Research Network (now a task force of the SRS) organized a workshop on informatics and data harmonization, presented at the World Sleep Congress 2019, in Vancouver, Canada. Experts in translational informatics gathered with sleep research experts to discuss opportunities and challenges in defining strategies for data harmonization. The goal of this workshop was to fuel discussion and foster innovative approaches for data integration and development of informatics infrastructure supporting multi-site collaboration. Key recommendations included collecting and storing findable, accessible, interoperable, and reusable data; identifying existing international cohorts and resources supporting research in sleep and circadian biology; and defining the most relevant sleep data elements and associated metadata that could be supported by early integration initiatives. This report introduces foundational concepts with the goal of facilitating engagement between the sleep/circadian and informatics communities and is a call to action for the implementation and adoption of data harmonization strategies in this domain.

Improvements in Cognitive Function and Quantitative Sleep EEG in OSA after Six Months of CPAP Treatment

Study Objectives Untreated obstructive sleep apnea (OSA) is associated with cognitive deficits and altered brain electrophysiology. We evaluated the effect of continuous positive airway pressure (CPAP) treatment on quantitative sleep electroencephalogram (EEG) measures and cognitive function. Methods We studied 162 OSA patients (age 50±13, AHI 35.0±26.8) before and after 6 months of CPAP. Cognitive tests assessed working memory, sustained attention, visuospatial scanning and executive function. All participants underwent overnight polysomnography at baseline and after CPAP. Power spectral analysis was performed on EEG data (C3-M2) in a sub-set of 90 participants. Relative delta EEG power and sigma power in NREM and EEG slowing in REM were calculated. Spindle densities (events p/min) in N2 were also derived using automated spindle event detection. All outcomes were analysed as change from baseline. Results Cognitive function across all cognitive domains improved after six months of CPAP. In our sub-set, increased relative delta power (p<0.0001) and reduced sigma power (p=0.001) during NREM were observed after the 6-month treatment period. Overall, fast and slow sleep spindle densities during N2 were increased after treatment. Conclusions Cognitive performance was improved and sleep EEG features were enhanced when assessing the effects of CPAP. These findings suggest the reversibility of cognitive deficits and altered brain electrophysiology observed in untreated OSA following six months of treatment.

Sleep deficiency in spaceflight is associated with degraded neurobehavioral functions and elevated stress in astronauts on six-month missions aboard the International Space Station

Astronauts are required to maintain optimal neurobehavioral functioning despite chronic exposure to the stressors and challenges of spaceflight. Sleep of adequate quality and duration is fundamental to neurobehavioral functioning, however astronauts commonly experience short sleep durations in spaceflight (<6 h). As humans embark on long-duration space exploration missions, there is an outstanding need to identify the consequences of sleep deficiency in spaceflight on neurobehavioral functions. Therefore, we conducted a longitudinal study that examined the sleep-wake behaviors, neurobehavioral functions, and ratings of stress and workload of N=24 astronauts before, during, and after 6-month missions aboard the International Space Station (ISS). The computerized, Reaction SelfTest (RST), gathered astronaut report of sleep-wake behaviors, stress, workload, and somatic behavioral states; the RST also objectively assessed vigilant attention (i.e., Psychomotor Vigilance Test-Brief). Data collection began 180 days before launch, continued every 4 days in-flight aboard the ISS, and up to 90 days post-landing, which produced N=2,856 RSTs. Consistent with previous ISS studies, astronauts reported sleeping ~6.5 h in-flight. The adverse consequences of short sleep were observed across neurobehavioral functions, where sleep durations <6 h were associated with significant reductions in psychomotor response speed, elevated stress, and higher workload. Sleep durations <5 h were associated with elevated negative somatic behavioral states. Furthermore, longer sleep durations had beneficial effects on astronaut neurobehavioral functions. Taken together, our findings highlight the importance of sleep for the maintenance of neurobehavioral functioning and as with humans on Earth, astronauts would likely benefit from interventions that promote sleep duration and quality.