Distribution of dim light melatonin offset (DLMOff) and phase relationship to waketime in healthy adults and associations with chronotype.

OBJECTIVES: Dim light melatonin onset, or the rise in melatonin levels representing the beginning of the biological night, is the gold standard indicator of circadian phase. Considerably less is known about dim light melatonin offset, or the decrease in melatonin to low daytime levels representing the end of the biological night. In the context of insufficient sleep, morning circadian misalignment, or energy intake after waketime but before dim light melatonin offset, is linked to impaired insulin sensitivity, suggesting the need to characterize dim light melatonin offset and identify risk for morning circadian misalignment. METHODS: We examined the distributions of dim light melatonin offset clock hour and the phase relationship between dim light melatonin offset and waketime, and associations between dim light melatonin offset, phase relationship, and chronotype in healthy adults (N = 62) who completed baseline protocols measuring components of the circadian melatonin rhythm and chronotype. RESULTS: 74.4% demonstrated dim light melatonin offset after waketime, indicating most healthy adults wake up before the end of biological night. Later chronotype (morningness-eveningness, mid-sleep on free days corrected, and average mid-sleep) was associated with later dim light melatonin offset clock hour. Later chronotype was also associated with a larger, positive phase relationship between dim light melatonin offset and waketime, except for morningness-eveningness. CONCLUSIONS: These findings suggest morning circadian misalignment risk among healthy adults, which would not be detected if only dim light melatonin onset were assessed. Chronotype measured by sleep timing may better predict this risk in healthy adults keeping a consistent sleep schedule than morningness-eveningness preferences. Additional research is needed to develop circadian biomarkers to predict dim light melatonin offset and evaluate appropriate dim light melatonin offset timing to promote health.

Enhancing untargeted metabolomics using metadata-based source annotation.

Human untargeted metabolomics studies annotate only ~10% of molecular features. We introduce reference-data-driven analysis to match metabolomics tandem mass spectrometry (MS/MS) data against metadata-annotated source data as a pseudo-MS/MS reference library. Applying this approach to food source data, we show that it increases MS/MS spectral usage 5.1-fold over conventional structural MS/MS library matches and allows empirical assessment of dietary patterns from untargeted data.

Sleep and Circadian Disruption and the Gut Microbiome-Possible Links to Dysregulated Metabolism.

Insufficient sleep and circadian misalignment are associated with adverse metabolic health outcomes. Alterations in gut microbial diversity occur with insufficient sleep and circadian misalignment, which can lead to modifications in microbial structure and function. Changes in microbially produced and modified metabolites such as short chain fatty acids and secondary bile acids may contribute to chronic inflammation, positive energy balance and endocrine changes, and represent potential mechanisms linking insufficient sleep and circadian misalignment with metabolic dysregulation. Literature primarily from the last two years is reviewed here, examining the impact of sleep and circadian rhythms and their disruption on the gut microbiome in human and non-human models, with an emphasis on the hypothesis that the altered gut microbiome may be one pathway by which insufficient sleep and circadian misalignment dysregulate metabolism.

Sleep in university students prior to and during COVID-19 Stay-at-Home orders.

Sleep health has multiple dimensions including duration, regularity, timing, and quality [1-4]. The Coronavirus 2019 (COVID-19) outbreak led to Stay-at-Home orders and Social Distancing Requirements in countries throughout the world to limit the spread of COVID-19. We investigated sleep behaviors prior to and during Stay-at-Home orders in 139 university students (aged 22.2 ± 1.7 years old [±SD]) while respectively taking the same classes in-person and remotely. During Stay-at-Home, nightly time in bed devoted to sleep (TIB, a proxy for sleep duration with regard to public health recommendations [5]) increased by ∼30 min during weekdays and by ∼24 mins on weekends and regularity of sleep timing improved by ∼12 min. Sleep timing became later by ∼50 min during weekdays and ∼25 min on weekends, and thus the difference between weekend and weekday sleep timing decreased - hence reducing the amount of social jetlag [6,7]. Further, we find individual differences in the change of TIB devoted to sleep such that students with shorter TIB at baseline before the first COVID-19 cases emerged locally had larger increases in weekday and weekend TIB during Stay-at-Home. The percentage of participants that reported 7 h or more sleep per night, the minimum recommended sleep duration for adults to maintain health [5] - including immune health - increased from 84% to 92% for weekdays during Stay-at-Home versus baseline. Understanding the factors underlying such changes in sleep health behaviors could help inform public health recommendations with the goal of improving sleep health during and following the Stay-at-Home orders of the COVID-19 pandemic.

Sleep and pain in humans with fibromyalgia and comorbid insomnia: double-blind, crossover study of suvorexant 20 mg versus placebo.

STUDY OBJECTIVES: The chronic pain disorder, fibromyalgia, is associated with sleep disturbance, typically sleep maintenance. No studies have evaluated the effect of sleep medication on pain sensitivity in this population. Suvorexant, an orexin antagonist approved for treatment of insomnia, was evaluated for effects on both sleep and the pain of fibromyalgia. METHODS: Women age 21 to 65 years with fibromyalgia and comorbid insomnia (n = 10) were treated, double-blind, for 9 nights each with suvorexant, 20 mg and placebo in counterbalanced order. All were in good psychiatric and stable physical health and met American College of Rheumatology 2010 criteria for fibromyalgia and Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition criteria for insomnia. Screening 8-hour polysomnography (PSG) was used to rule out other sleep disorders. On nights 8 and 9 of each treatment 8-hour PSG were collected and on days 1 and 8 pain sensitivity was assessed at 1100 and 1500 hours by measuring finger withdrawal latency (FWL) to a radiant heat stimulus at 5 randomly presented intensity levels. RESULTS: Suvorexant versus placebo increased total sleep time (7.2 versus 6.7 hours, P < .05) and reduced wake after sleep onset (37 versus 67 minutes, P < .04) with no night effects or interaction. Latency to persistent sleep and sleep stage measures were not altered. FWL on both am and pm tests varied as a function of intensity (P < .001). Average FWL (over 5 intensities and both days) was increased relative to placebo on both the am (13.9 versus 13.1 seconds) and pm tests (15.8 versus 14.1 seconds, P < .03) following suvorexant the previous night. CONCLUSIONS: Suvorexant 20 mg in patients with fibromyalgia, improved sleep time and reduced next-day pain sensitivity on assessments of FWL to a radiant heat stimulus. CLINICAL TRIAL REGISTRY: Registry: ClinicalTrials.gov; Name: A double-blind cross-over, study to compare the hypnotic, daytime sleepiness/fatigue, and pain effects of nighttime administration of suvorexant 20 mg versus placebo in patients with fibromyalgia and comorbid insomnia; Identifier: NCT02684136; URL: https://clinicaltrials.gov/ct2/show/NCT02684136.

Relation between ambulatory actigraphy and laboratory polysomnography in insomnia practice and research.

Actigraphy is increasingly used in practice and research studies because of its relative low cost and decreased subject burden. How multiple nights of at-home actigraphy compare to one independent night of in-laboratory polysomnography (PSG) has not been examined in people with insomnia. Using event markers (MARK) to set time in bed (TIB) compared to automatic program analysis (AUTO) has not been systematically evaluated. Subjects (n = 30) meeting DSM-5 criteria for insomnia and in-laboratory PSG sleep efficiency (SE) of <85% were studied. Subjects were free of psychiatric, sleep or circadian disorders, other chronic conditions and medications that effect sleep. Subjects had an in-laboratory PSG, then were sent home for 7 nights with Philips Actiwatch Spectrum Plus. Data were analysed using Philips Actiware version 6. Using the mean of seven nights, TIB, total sleep time (TST), SE, sleep-onset latency (SOL) and wake after sleep onset (WASO) were examined. Compared to PSG, AUTO showed longer TIB and TST and less WASO. MARK only differed from PSG with decreased WASO. Differences between the PSG night and the following night at home were found, with better sleep on the first night home. Actigraphy in people with insomnia over seven nights is a valid indicator of sleep compared to an independent in-laboratory PSG. Event markers increased the validity of actigraphy, showing no difference in TIB, TST, SE and SOL. AUTO was representative of SE and SOL. Increased SE and TST without increased TIB suggests possible compensatory sleep the first at night home after in-laboratory PSG.