Introduction: Although glucose tolerance in healthy individuals is higher in the morning vs. evening, the potential role of the endogenous circadian system, independent of light-dark and behavioral (e.g., sleep, eating) cycles, has not been tested using a gold-standard circadian protocol. Furthermore, it is unclear whether such endogenous circadian rhythm in glucose tolerance can be synchronized by prior eating times in humans. In addition, there is a clear knowledge gap in circadian influences on postprandial insulin responses, in particular early-phase insulin as a measure of pancreatic beta-cell function. We tested the hypotheses that there exists an endogenous circadian rhythm in glucose tolerance and early-phase insulin, and that these rhythms can be phase-shifted by a prior history of delayed mealtimes. Methods: In a randomized crossover trial, 16 adults with overweight/obesity and without diabetes (11 men, age 37±11 y, BMI 28.8±2.4 kg·m-2, HbA1c 5.4±0.4 %; mean±SD) completed two 8-day in-laboratory protocols: an early eating (EE, 4 days) and a late eating (LE, 4 days) condition, in random order and including a washout. Each condition was preceded by a 5-day EE baseline and followed by a Constant Routine (CR) procedure. Both protocols were identical for behavioral (sleep, physical activity, posture) and environmental (lighting, temperature) conditions and timing. Three identical test meals were consumed 4h:10m apart, with all meals delayed by 4h:10m in LE vs. EE. We then assessed the endogenous circadian rhythmicity in glucose tolerance using 36-h CR protocols (i.e., continuous wakefulness, semi-recumbent posture, dim light, and test meals every 6h) to isolate the endogenous circadian glucose and insulin responses. Using the last five of six CR test meals, glucose tolerance and early-phase insulin were quantified from 3-h postprandial incremental area under the curves (iAUCs) of serum glucose concentrations and first 30-min of serum insulin concentrations, respectively. Individual endogenous circadian phase was derived from core body temperature (CBT) measurements made throughout the CR. Circadian rhythm phase and amplitude of main outcomes was derived from cosinor analysis of normalized (across circadian cycle) iAUC using mixed model analyses of variance. Results: There was no difference in the timing of CBT nadir after EE and LE (p>0.05). The peak-to-trough amplitudes in normalized 3-h postprandial glucose and 30-min early-phase insulin iAUC were 36% (p< 0.001) and 32% (p=0.016) of the mean across circadian cycle, respectively, after EE, with the highest and lowest glucose tolerance (~5 AM/~5 PM) and early-phase insulin response (~7 AM/~7 PM) in the biological morning and evening, respectively. After LE, the peak-to-trough amplitudes in normalized 3-h postprandial glucose and 30-min early-phase insulin iAUC were 35% (p< 0.05) and 39% (p=0.001) of the mean across circadian cycle, respectively, with a significant phase delay in i) glucose tolerance by ~60° (~4h; circadian rhythm-protocol interaction p< 0.05), and ii) early-phase insulin by ~90° (~6h; rhythm-protocol interaction p=0.002). Conclusion: Our findings demonstrated in people with overweight or obesity that glucose tolerance and early-phase insulin expressed a robust endogenous circadian rhythm in glucose tolerance and early-phase insulin that peaks in the biological morning and reaches a trough in the evening. Notably, this study revealed a gradual decoupling of central (core body temperature) and peripheral (glucose and insulin) circadian rhythms, by demonstrating a synchronization of glucose and insulin rhythmicity to eating schedules, with no change in central rhythmicity, over four days. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Autism and attention-deficit hyperactivity disorder (ADHD) are among the most common neurodivergent neurotypes worldwide. Epidemiological evidence shows that sleep and circadian disturbances, such as difficulty initiating and maintaining sleep, and delayed sleep-wake phase, are highly prevalent in autistic children, children with ADHD, and those with both neurotypes. Despite scientific advancements, a comprehensive framework integrating sleep and circadian mechanisms with targeted interventions for autism and ADHD remains underdeveloped. In this Review we examine sleep and circadian rhythm differences in autistic children and adolescents, and in those with ADHD or both neurotypes, focusing on the underlying biological mechanisms. We discuss recent advances in the genetic and molecular links between sleep, circadian rhythms, and neuroplasticity, alongside the influence of these systems on physiology and therapeutic strategies. Both pharmacological and non-pharmacological interventions are considered, with an emphasis on the need for an integrated support model that accounts for the dynamic interplay between sleep and circadian rhythms in these populations. We identify key gaps in the current evidence base, particularly in relation to non-pharmacological interventions, and outline future research directions. Although most randomised controlled trials in children and adolescents have focused on behavioural sleep interventions, we also discuss emerging findings from trials using alternative approaches, such as targeted light therapy in adults, with implications for paediatric populations. Finally, we emphasise the importance of incorporating the perspectives of autistic children and adolescents and those with ADHD, as well as their parents and caregivers, into research designs.

Introduction and Objective: Glucose tolerance is lower in the evening/night vs morning. Consequently, a later meal schedule may impair glucose tolerance and/or 24-h glycemia, both T2DM risk factors. We determine if late vs early eating increases 24-h, daytime, nighttime, and postprandial blood glycemia. Methods: In a randomized crossover trial, 13 adults (4 women, age 37±12 y, BMI 29.2 ± 2.3 kg·m-2, HbA1c 5.4 ± 0.4 %; mean ± SD) completed 2 experimental conditions - early (EE) and late eating (LE) after a 5-d EE baseline that controlled for behavioral (sleep, physical activity) and environmental influences. Three identical/isocaloric test meals (45-50% CHO, 15-20% PRO, 30-35% FAT, GI 60-65, per 24 h) were consumed 4h:10m apart, with all meals delayed by 4h:10m in LE vs EE. Serum glucose and insulin concentrations were used to derive their total 24-h, 16-h day/wake, 8-h night/sleep, and postprandial iAUCs. Paired, two-tailed test was the main statistical analysis. Results: Twenty four-hour blood glycemia increased 3% in LE vs EE (P = 0.03), with a more distinct 9% increase during sleep (P = 0.0001) but without a significant difference during the wake episode. Insulinemia was 5% lower in LE vs. EE during wake (P = 0.0017) with no significant difference during sleep and over 24 h. Three-hour glycemic excursion was 87% greater (P = 0.0005) for the first meal on test day when it was eaten after an extended fast (~20 h) in LE vs EE (~16 h). Although a difference in insulin 3-h iAUC was not observed for this first meal, early phase (40 min post meal) insulin response was 42% lower in LE vs EE (P = 0.0003). Conclusion: Our findings suggest that irregular/sporadic late eating occurrence elevates 24-h blood glycemia, especially during sleep, in people with overweight/obesity. In addition, postprandial insulin response to the first meal appears impaired after an extended overnight fast. Further research is warranted to determine if these acute adverse effects impact long-term glucose control in at-risk populations, and if they persist after consecutive late eating episodes. H. Koh: None. N. Vujovic: Employee; Novartis Pharmaceuticals Corporation. Stock/Shareholder; Novartis Pharmaceuticals Corporation. S.L. Chellappa: None. J. Qian: None. M. Butler: None. S. Heng: None. N. Rahman: None. F.A. Scheer: None. NIH (R01-DK099512)

Effective countermeasures against the adverse cardiovascular effects of circadian misalignment, such as effects experienced due to night work or jet lag, remain to be established in humans. Here, we aim to test whether eating only during daytime can mitigate such adverse effects vs. eating during the night and day (typical for night shift workers) under simulated night work (secondary analysis of NCT02291952). This single-blind, parallel-arm trial randomized 20 healthy participants (non-shift workers) to simulated night work with meals consumed during night and day (Nighttime Meal Control Group) or only during daytime (Daytime Meal Intervention Group). The primary outcomes were pNN50 (percentage consecutive heartbeat intervals >50 ms), RMSSD (root mean square of successive heartbeat differences), and LF/HF (low/high cardiac frequency). The secondary outcome was blood concentrations of prothrombotic factor plasminogen activator inhibitor-1 (PAI-1). These measures were assessed under Constant Routine conditions, before (baseline) and after (postmisalignment) simulated night work. The meal timing intervention significantly modified the impact of simulated night work on cardiac vagal modulation and PAI-1 (pFDR = 0.001). In the Control Group, the postmisalignment Constant Routine showed a decrease in pNN50 by 25.7% (pFDR = 0.008) and RMMSD by 14.3% (pFDR = 0.02), and an increase in LF/HF by 5.5% (pFDR = 0.04) and PAI-1 by 23.9% (pFDR = 0.04), vs. the baseline Constant Routine. In the Intervention Group, there were no significant changes in these outcomes. For exploratory outcomes, the intervention significantly modified the impact of simulated night work on blood pressure (P < 0.05), with no significant change in the Control Group, and a significant reduction by 6-8% (P < 0.01) in the Intervention Group; without significant effects for heart rate or cortisol. These findings indicate that daytime eating, despite mistimed sleep, may mitigate changes in cardiovascular risk factors and offer translational evidence for developing a behavioral strategy to help minimize the adverse changes in cardiovascular risk factors in individuals exposed to circadian misalignment, such as shift workers.

The estimated prevalence of autism spectrum disorder in individuals over 8 years is currently one in 44, with applied behavioural analysis being the most commonly used state-funded form of treatment for autism in the USA.1American Medical AssociationRevision of H-185.921, Removal of AMA Support for Applied Behavior Analysis.https://www.ama-assn.org/system/files/a23-706.pdfDate: April 3, 2023Date accessed: November 14, 2023Google Scholar Part of its widespread availability is the policy of the American Medical Association (AMA), which supported applied behavioural analysis as the first choice evidence-based treatment for autism.1American Medical AssociationRevision of H-185.921, Removal of AMA Support for Applied Behavior Analysis.https://www.ama-assn.org/system/files/a23-706.pdfDate: April 3, 2023Date accessed: November 14, 2023Google Scholar However, at the AMA House of Delegates annual meeting in June, 2023, Resolution 706 entitled, “Revision of H-185.921, removal of AMA support for applied behavior analysis”,1American Medical AssociationRevision of H-185.921, Removal of AMA Support for Applied Behavior Analysis.https://www.ama-assn.org/system/files/a23-706.pdfDate: April 3, 2023Date accessed: November 14, 2023Google Scholar put forward two changes.1American Medical AssociationRevision of H-185.921, Removal of AMA Support for Applied Behavior Analysis.https://www.ama-assn.org/system/files/a23-706.pdfDate: April 3, 2023Date accessed: November 14, 2023Google Scholar First, they recommended a policy change, including the removal of language recommending applied behavioural analysis coverage; second, they replaced the wording “treatment of” with “services for” autism spectrum disorder, a language choice that better supports neuroinclusivity. Central to AMA's policy change was its recognition of the controversial nature of applied behavioural analysis within the autism rights movement, as well as the risks of applied behavioural analysis to mental health. Such risks include post-traumatic stress disorder in autistic adults who received applied behavioural analysis as children.2Kupferstein H Evidence of increased PTSD symptoms in autistics exposed to applied behavior analysis.Adv Autism. 2018; 4: 19-29Crossref Scopus (63) Google Scholar The focus of applied behavioural analysis on suppressing autistic behaviours is a widespread clinical practice, particularly in the USA,3Center for Disease Control and Prevention (CDC)Autism Spectrum Disorder.https://www.cdc.gov/ncbddd/autism/index.htmlDate: March 31, 2023Date accessed: November 14, 2023Google Scholar despite weak Cochrane review evidence supporting this practice.4Reichow B Hume K Barton EE Boyd BA Early intensive behavioral intervention (EIBI) for young children with autism spectrum disorders (ASD).Cochrane Database Syst Rev. 2018; 5CD009260PubMed Google Scholar The AMA Resolution 706 argues that the goal of making autistic individuals indistinguishable from one's peers can undermine their sense of identity and humanity.1American Medical AssociationRevision of H-185.921, Removal of AMA Support for Applied Behavior Analysis.https://www.ama-assn.org/system/files/a23-706.pdfDate: April 3, 2023Date accessed: November 14, 2023Google Scholar Consequently, alternative neuroaffirmative behavioural approaches to applied behavioural analysis, such as the developmental, individual differences, and relationship-based programme, and individualised early social interaction, were less accessible to autistic people and their families.1American Medical AssociationRevision of H-185.921, Removal of AMA Support for Applied Behavior Analysis.https://www.ama-assn.org/system/files/a23-706.pdfDate: April 3, 2023Date accessed: November 14, 2023Google Scholar The new policy substantially reduces the explicit support for applied behavioural analysis and will, I hope, open the door for autistic-led, evidence-based services. What are the expected outcomes from such a change? First, caution is warranted. As of now, this is a recommended policy change that is within the medical disability model, not the (self-advocate led) social disability model. The medical disability model frames autism as an impairment that causes autistic people to have restricted or no access to goods and services or not be able to participate fully in society. Conversely, the social disability model–adopted by most autism organisations5Olkin R Could you hold the door for me? Including disability in diversity.Cultur Divers Ethnic Minor Psychol. 2002; 8: 130-137Crossref PubMed Scopus (66) Google Scholar–frames autism as a disability due to barriers erected by society that can impede autistic people from participating fully in daily life.5Olkin R Could you hold the door for me? Including disability in diversity.Cultur Divers Ethnic Minor Psychol. 2002; 8: 130-137Crossref PubMed Scopus (66) Google Scholar Although the current AMA-recommended policy changes still allow applied behavioural analysis to be a treatment option, it is a necessary first step to more research into evidence-based services that are designed by and support autistic people, instead of treatment options aimed at a cure or conversion. This policy change leads to the second–and equally important–step: the acknowledgment that an autistic person needs support services, not treating and fixing. Lastly, Resolution 706 proposes the use of diversity-focused language (eg, neurodivergent) as opposed to phrases, such as individuals suffering with autism spectrum disorder, in line with the neurodiversity movement. As a neurodivergent self-advocate and researcher, I see the AMA-recommended policy changes as reaffirming the belief that neuroaffirmative support is crucial for autistic individuals to be their authentic selves. This is a victory for us, self-advocates, who have been working to raise awareness about the need to stop modification of so-called undesirable behaviours as the main goal of clinical research and treatment for autistic people.4Reichow B Hume K Barton EE Boyd BA Early intensive behavioral intervention (EIBI) for young children with autism spectrum disorders (ASD).Cochrane Database Syst Rev. 2018; 5CD009260PubMed Google Scholar Embracing effective, neurodivergent-led support services that are not based on compliance, coercion, or attempting to cure autism, and that do not increase mental health risks, will lead to a welcome and much needed wind of change. The author declares no conflict of interest.

The number of individuals experiencing sleep loss has exponentially risen over the past decades. Extrapolation of laboratory findings to the real world suggests that females are more affected by extended wakefulness and circadian misalignment than males are. Therefore, long-term effects such as sleep and metabolic disorders are likely to be more prevalent in females than in males. Despite emerging evidence for sex differences in key aspects of sleep-wake and circadian regulation, much remains unknown, as females are often underrepresented in sleep and circadian research. This narrative review aims at highlighting 1) how sex differences systematically impinge on the sleep-wake and circadian regulation in humans, 2) how sex differences in sleep and circadian factors modulate metabolic control, and 3) the relevance of these differences for precision medicine. Ultimately, the findings justify factoring in sex differences when optimizing individually targeted sleep and circadian interventions in humans.

Sleep, circadian rhythms, and mental health are reciprocally interlinked. Disruption to the quality, continuity, and timing of sleep can precipitate or exacerbate psychiatric symptoms in susceptible individuals, while treatments that target sleep—circadian disturbances can alleviate psychopathology. Conversely, psychiatric symptoms can reciprocally exacerbate poor sleep and disrupt clock-controlled processes. Despite progress in elucidating underlying mechanisms, a cohesive approach that integrates the dynamic interactions between psychiatric disorder with both sleep and circadian processes is lacking. This review synthesizes recent evidence for sleep—circadian dysfunction as a transdiagnostic contributor to a range of psychiatric disorders, with an emphasis on biological mechanisms. We highlight observations from adolescent and young adults, who are at greatest risk of developing mental disorders, and for whom early detection and intervention promise the greatest benefit. In particular, we aim to a) integrate sleep and circadian factors implicated in the pathophysiology and treatment of mood, anxiety, and psychosis spectrum disorders, with a transdiagnostic perspective; b) highlight the need to reframe existing knowledge and adopt an integrated approach which recognizes the interaction between sleep and circadian factors; and c) identify important gaps and opportunities for further research.

Gender equality in academia still faces enduring challenges globally, with under-representation of women in leadership and decision-making positions. However, most universities and research institutions actively implement gender equality plans and undertake activities aimed at increasing it. Despite this remarkable progress, intersectionality lags behind. This term, first coined by Kimberlé Crenshaw, corresponds to the "lens through which you can see where power comes and collides, where it interlocks and intersects".1Crenshaw K Demarginalizing the intersection of race and sex: a Black feminist critique of antidiscrimination doctrine, feminist theory and antiracist politics.in: Bartlett K Feminist legal theory. Routledge, New York, NY1991Google Scholar Intersectionality conceptualises that there are multiple simultaneous sources of oppression: race, class, gender identity, sexual orientation, neurodivergence, and other identity markers that can create a complex web of oppression. For instance, women from under-represented minorities experience the interplay of sexism, racism, and, for example, ableism (as in the case of autistic scientists) in science, technology, engineering, and mathematics (STEM). This is because white neurotypical men are historically over-represented in the STEM academic fields.2Cech E The intersectional privilege of white able-bodied heterosexual men in STEM.Sci Adv. 2022; 8eabo1558Crossref PubMed Scopus (16) Google Scholar The consequent brain drain often commences with outright aggression and discriminatory behaviours, sexism, racism, insufficient institutional and grant support, and inadequate working arrangements for individuals' unique needs. The consequences of this inequity are dire: women of colour, particularly those who are LBTQ+ and with a disability, are seldom promoted in academic institutions and may leave science altogether.2Cech E The intersectional privilege of white able-bodied heterosexual men in STEM.Sci Adv. 2022; 8eabo1558Crossref PubMed Scopus (16) Google Scholar Therefore, intersectionality must be a focus in research and academia to ensure real equity and prosperity. To incorporate an intersectional perspective, we need to reconstruct universities and research institutions, often built on racist, misogynist, and colonial ideals. Despite policy efforts targeted at making universities more inclusive and equitable, academia is still rife with discrimination, institutional resistance to intersectional equity, and retaliation against reporters of misconduct in universities and research institutions. This adverse scenario is particularly so for women academics from under-represented minorities that differ from the majority on multiple dimensions and are the ones who show a stronger and more negative relationship between policy ineffectiveness and psychological safety.3Kozlowski D Larivière V Sugimoto CR Monroe-White T Intersectional inequalities in science.PNAS. 2023; 119e2113067119Google Scholar What can we do? A coordinated, consistent, and sustained effort with policy makers, grant holders, universities, and research institutions—with the active participation of scientists with intersecting minority identities—is the first step in a complex and multifaceted roadmap against injustice. The next step is to create an inclusive career development framework, acknowledging intersectional identities to monitor and support the career progression of marginalised academics, thus ensuring progression from early career fellowships to full professor appointments in STEM.4Tauber S Women academics' intersectional experiences of policy ineffectiveness in the European context.Fron Psychol. 2022; 13810569PubMed Google Scholar Finally, yet importantly, policy makers, academic journals, grant holders, universities, and research institutions must publicly endorse and push forward intersectionality to increase diversity in academia. SLC is funded by the Alexander Von Humboldt Foundation; the funder had no role in the writing of the Correspondence or the decision to publish it.

Sleep has been suggested to contribute to myelinogenesis and associated structural changes in the brain. As a principal hallmark of sleep, slow-wave activity (SWA) is homeostatically regulated but also differs between individuals. Besides its homeostatic function, SWA topography is suggested to reflect processes of brain maturation. Here, we assessed whether interindividual differences in sleep SWA and its homeostatic response to sleep manipulations are associated with in-vivo myelin estimates in a sample of healthy young men. Two hundred twenty-six participants (18-31 y.) underwent an in-lab protocol in which SWA was assessed at baseline (BAS), after sleep deprivation (high homeostatic sleep pressure, HSP) and after sleep saturation (low homeostatic sleep pressure, LSP). Early-night frontal SWA, the frontal-occipital SWA ratio, as well as the overnight exponential SWA decay were computed over sleep conditions. Semi-quantitative magnetization transfer saturation maps (MTsat), providing markers for myelin content, were acquired during a separate laboratory visit. Early-night frontal SWA was negatively associated with regional myelin estimates in the temporal portion of the inferior longitudinal fasciculus. By contrast, neither the responsiveness of SWA to sleep saturation or deprivation, its overnight dynamics, nor the frontal/occipital SWA ratio were associated with brain structural indices. Our results indicate that frontal SWA generation tracks inter-individual differences in continued structural brain re-organization during early adulthood. This stage of life is not only characterized by ongoing region-specific changes in myelin content, but also by a sharp decrease and a shift towards frontal predominance in SWA generation.

OBJECTIVES:We examined whether the endogenous circadian timing system modulates proxies of mood vulnerability and well-being. METHODS:Nineteen healthy participants (mean age: 26.6 years [23.0-30.2], seven females, body-mass index: 22.8 kg/m2 [21.1-25]) completed a laboratory protocol with a 32-hour Constant Routine, a stringently controlled protocol designed to isolate assessment of endogenous circadian rhythms. We assessed hourly anxiety- and depression-like mood (i.e., those typically observed in depression and anxiety) and well-being (i.e., associated with mental fatigue and physical comfort). RESULTS:Significant endogenous circadian rhythms were observed in anxiety-like and depression-like mood, as well as well-being (p values from the mixed-model analysis using false discovery rates < .001). Post-hoc comparisons revealed more anxiety-like and depression-like mood during the circadian phase 60°-75° (∼8-9 a.m.), and more mental fatigue and less physical comfort during the circadian phase 30°-60° (∼6-8 a.m.). CONCLUSIONS:Our data indicate endogenous circadian rhythms in anxiety-like and depression-like mood and well-being in healthy young adults. Future studies will help establish circadian-based therapeutics for individuals experiencing mood and anxiety disorders.

Research on the mental rotation task has sparked debate regarding the specific processes that underly the capability of humans to mentally rotate objects. The spread of reported brain activations suggests that mental rotation is subserved by a neural network circle. However, no common network has yet been found that uncovers the crucial processes underlying this ability. We aimed to identify the common network crucial for mental rotation by coordinate-based network mapping of previous neuroimaging findings in mental rotation. A meta-analysis revealed 710 peak activation coordinates from 42 fMRI studies in mental rotation, which include a total 844 participants. The coordinates were mapped to a normative functional connectome (n = 1000) to identify a network of connected regions. To account for experimental factors, we examined this network against two control tasks, action imitation and symbolic number processing. A common and crucial network for mental rotation, centring on dorsal premotor, superior parietal and inferior temporal lobes was revealed. This network, separated from other experimental aspects, suggests that the crucial processes underlying mental rotation are motor rotation, visuospatial processing, and higher order visual object recognition.

OBJECTIVES:Acute and chronic sleep loss and circadian timing interact such that, depending on their combination, small or very large performance decrements are observed in tasks of attention. Here, we tested whether such nonlinear interactions extend to a physiological measure of spontaneous visual attentional failures, indicating a fundamental principle of sleep-wake regulation. METHODS:Nine healthy volunteers completed an in-laboratory 3-week forced desynchrony protocol consisting of 12 consecutive 42.85-hour cycles with a sleep-wake ratio of 1:3.3. The protocol induced increasing chronic sleep loss, while extended wake (32.85 hours) and sleep episodes (10 hours) occurred at multiple circadian phases. Attentional failure rate was quantified from continuous electrooculograms (number of 30-second epochs with slow eye movements/h of wakefulness) as a function of time since scheduled wake (acute sleep loss), week of study (chronic sleep loss), and circadian (melatonin) phase. RESULTS:During the first ∼8 hours awake, attentional failure rate was low, irrespective of the week. During the following wake hours, attentional failure rate increased steadily but at a faster rate in weeks 2 and 3 compared to week 1. The effects of acute and chronic sleep loss on attentional failure rate were magnified during the biological night compared to the biological day. CONCLUSIONS:A single extended sleep episode can only temporarily reverse attentional impairment associated with chronic sleep loss. Multiplicative effects of acute and chronic sleep loss-further amplified during the biological night-substantiate the interaction of 2 homeostatic response mechanisms and caution against underestimating their disproportionate combined impact on performance, health, and safety.

OBJECTIVE:Sleep varies between individuals in response to sleep-wake history and various environmental factors, including light and noise. Here we report on the intranight variation of the ultradian nonrapid eye movement-rapid eye movement (NREM-REM) sleep cycle in 369 participants who have contributed to different laboratory studies from 1994 to 2020 at the Centre for Chronobiology, Basel, Switzerland. RESULTS:We observed a large interindividual variability in sleep cycle duration, including NREM and REM sleep episodes in healthy participants who were given an 8-hour sleep opportunity at habitual bedtime in controlled laboratory settings. The median sleep cycle duration was 96 minutes out of 6064 polysomnographically-recorded cycles. The number and duration of cycles were not normally distributed, and the distribution became narrower for NREM sleep and wider for REM sleep later in the night. The first cycle was consistently shorter than subsequent cycles, and moderate presleep light or nocturnal noise exposure had no significant effects on ultradian sleep cycle duration. Age and sex significantly affected NREM and REM sleep duration, with older individuals having longer NREM and shorter REM sleep particularly in the end of the night, and females having longer NREM sleep episodes. High sleep pressure (ie, sleep deprivation) and low sleep pressure (ie, multiple naps) altered ultradian sleep cycles, with high sleep pressure leading to longer NREM sleep in the first cycle, and low sleep pressure leading to longer REM sleep episodes. Positive correlations were observed between N2 and NREM duration, and between N1 and REM duration. Weak intrasleep REM sleep homeostasis was also evident in our data set. CONCLUSIONS:We conclude that ultradian sleep cycles are endogenous biological rhythms modulated by age, sex, and sleep homeostasis, but not directly responsive to (moderate levels of) environmental cues in healthy good sleepers.

Evening exposure to electric light can acutely suppress melatonin levels and adversely affect subsequent sleep. We conducted a systematic review with meta-analysis investigating the influence of evening illuminance levels on polysomnographically (PSG)-assessed sleep. We also explored how melanopsin (expressed in melanopic equivalent daylight illuminance (EDI) affects human sleep features. We included polysomnographic laboratory sleep studies with healthy humans for effects of illuminance and exposure duration, for pre-sleep exposures between 6:00 p.m. to 1:00 a.m. From 440 identified articles, 114 met eligibility criteria for screening, and 21 also reported type of light source/spectral characteristics, with 12 identified as eligible for review. Meta-analysis showed evening light affects sleep latency, sleep efficiency and slow wave sleep, with overall effect sizes (95% confidence interval) of 0.69 (−0.50; 1.88), 0.34 (−0.13; 0.82) and −0.61 (−1.85; 0.62), respectively. Estimated melanopic EDI in the range of 100–1000 lx yielded clear dose–response relationships for sleep latency and sleep efficiency, but not for slow wave sleep. Whilst illuminance and duration indicated no apparent effects for a single evening light exposure on PSG-assessed sleep latency, sleep efficiency and slow wave sleep, we observed evidence for a relationship between light exposure and sleep effects based on melanopic EDI. Hence, melanopic EDI may provide a robust predictor of non-visual responses on human sleep.

Anxiety is the most common mental health problem worldwide. Epidemiological studies show that sleep disturbances, particularly insomnia, affect ∼50% of individuals with anxiety, and that insufficient sleep can instigate or further exacerbate it. This review outlines brain mechanisms underlying sleep and anxiety, by addressing recent human functional/structural imaging studies on brain networks underlying the anxiogenic impact of sleep loss, and the beneficial effect of sleep on these brain networks. We discuss recent developments from human molecular imaging studies that highlight the role of specific brain neurotransmitter mechanisms, such as the adenosinergic receptor system, on anxiety, arousal, and sleep. This review further discusses frontline sleep interventions aimed at enhancing sleep in individuals experiencing anxiety, such as nonbenzodiazepines/antidepressants, lifestyle and sleep interventions and cognitive behavioral therapy for insomnia. Notwithstanding therapeutic success, up to ∼30% of individuals with anxiety can be nonresponsive to frontline treatments. Thus, we address novel non-invasive brain stimulation techniques that can enhance electroencephalographic slow waves, and might help alleviate sleep and anxiety symptoms. Collectively, these findings contribute to an emerging biological framework that elucidates the interrelationship between sleep and anxiety, and highlight the prospect of slow wave sleep as a potential therapeutic target for reducing anxiety.