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.

Over the past 40 years, actigraphy has been used to study rest-activity patterns in circadian rhythm and sleep research. Furthermore, considering its simplicity of use, there is a growing interest in the analysis of large population-based samples, using actigraphy. Here, we introduce pyActigraphy, a comprehensive toolbox for data visualization and analysis including multiple sleep detection algorithms and rest-activity rhythm variables. This open-source python package implements methods to read multiple data formats, quantify various properties of rest-activity rhythms, visualize sleep agendas, automatically detect rest periods and perform more advanced signal processing analyses. The development of this package aims to pave the way towards the establishment of a comprehensive open-source software suite, supported by a community of both developers and researchers, that would provide all the necessary tools for in-depth and large scale actigraphy data analyses.

We examined whether ambient lighting conditions during extended wakefulness modulate the homeostatic response to sleep loss as indexed by. slow wave sleep (SWS) and electroencephalographic (EEG) slow-wave activity (SWA) in healthy young and older volunteers. Thirty-eight young and older participants underwent 40 hours of extended wakefulness [i.e., sleep deprivation (SD)] once under dim light (DL: 8 lux, 2800 K), and once under either white light (WL: 250 lux, 2800 K) or blue-enriched white light (BL: 250 lux, 9000 K) exposure. Subjective sleepiness was assessed hourly and polysomnography was quantified during the baseline night prior to the 40-h SD and during the subsequent recovery night. Both the young and older participants responded with a higher homeostatic sleep response to 40-h SD after WL and BL than after DL. This was indexed by a significantly faster intra-night accumulation of SWS and a significantly higher response in relative EEG SWA during the recovery night after WL and BL than after DL for both age groups. No significant differences were observed between the WL and BL condition for these two particular SWS and SWA measures. Subjective sleepiness ratings during the 40-h SD were significantly reduced under both WL and BL compared to DL, but were not significantly associated with markers of sleep homeostasis in both age groups. Our data indicate that not only the duration of prior wakefulness, but also the experienced illuminance during wakefulness affects homeostatic sleep regulation in humans. Thus, working extended hours under low illuminance may negatively impact subsequent sleep intensity in humans.

Sleep loss affects human behavior in a nonuniform manner, depending on the cognitive domain and also the circadian phase. Besides, evidence exists about stable interindividual variations in sleep loss–related performance impairments. Despite this evidence, only a few studies have considered both circadian phase and neurobehavioral domain when investigating trait-like vulnerability to sleep manipulation. By applying a randomized, crossover design with 2 sleep pressure conditions (40 h sleep deprivation vs. 40 h multiple naps), we investigated the influence of a human adenosine deaminase (ADA) polymorphism (rs73598374) on several behavioral measures throughout nearly 2 circadian cycles. Confirming earlier studies, we observed that under sleep deprivation the previously reported vulnerable G/A-allele carriers felt overall sleepier than G/G-allele carriers. As expected, this difference was no longer present when sleep pressure was reduced by the application of multiple naps. Concomitantly, well-being was worse in the G/A genotype under sleep loss when compared to the nap protocol, and n-back working memory performance appeared to be specifically susceptible to sleep-wake manipulation in this genotype. When considering psychomotor vigilance performance, however, a higher sensitivity to sleep-wake manipulation was detected in homozygous participants, but specifically at the end of the night and only for optimal task performance. Although these data are based on a small sample size and hence require replication (12 G/A- and 12 G/G-allele carriers), they confirm the assumption that interindividual differences regarding the effect of sleep manipulation highly depend on the cognitive task and circadian phase, and thus emphasize the necessity of a multimethodological approach. Moreover, they indicate that napping might be suitable to counteract endogenously heightened sleep pressure depending on the neurobehavioral domain.

Study Objectives: Daytime napping is frequently reported among the older population and has attracted increasing attention due to its association with multiple health conditions. Here, we tested whether napping in the aged is associated with altered circadian regulation of sleep, sleepiness, and vigilance performance. Methods: Sixty healthy older individuals (mean age: 69 years, 39 women) were recruited with respect to their napping habits (30 nappers, 30 non-nappers). All participants underwent an in-lab 40-hour multiple nap protocol (10 cycles of 80 minutes of sleep opportunity alternating with 160 minutes of wakefulness), preceded and followed by a baseline and recovery sleep period. Saliva samples for melatonin assessment, sleepiness, and vigilance performance were collected during wakefulness and electrophysiological data were recorded to derive sleep parameters during scheduled sleep opportunities. Results: The circadian amplitude of melatonin secretion was reduced in nappers, compared to non-nappers. Furthermore, nappers were characterized by higher sleep efficiencies and REM sleep proportion during day- compared to nighttime naps. The nap group also presented altered modulation in sleepiness and vigilance performance at specific circadian phases. Discussion: Our data indicate that napping is associated with an altered circadian sleep–wake propensity rhythm. They thereby contribute to the understanding of the biological correlates underlying napping and/or sleep–wake cycle fragmentation during healthy aging. Altered circadian sleep–wake promotion can lead to a less distinct allocation of sleep into nighttime and/or a reduced wakefulness drive during the day, thereby potentially triggering the need to sleep at adverse circadian phase.

BACKGROUND: Neuronal hyperexcitability characterizes the early stages of Alzheimer’s disease (AD). In animals, early misfolded tau and amyloid-β (Aβ) protein accumulation — both central to AD neuropathology — promote cortical excitability and neuronal network dysfunction. In healthy humans, misfolded tau and Aβ aggregates are first detected, respectively, in the brainstem and frontomedial and temporobasal cortices, decades prior to the onset of AD cognitive symptoms. Whether cortical excitability is related to early brainstem tau — and its associated neuroinflammation — and cortical Aβ aggregations remains unknown. METHODS: We probed frontal cortex excitability, using transcranial magnetic stimulation combined with electroencephalography, in a sample of 64 healthy late-middle–aged individuals (50–69 years; 45 women and 19 men). We assessed whole-brain ^[18F] THK5351 PET uptake as a proxy measure of tau/neuroinflammation, and we assessed whole-brain Aβ burden with ^[18F] Flutemetamol or ^[18F] Florbetapir radiotracers. RESULTS: We found that higher ^[18F] THK5351 uptake in a brainstem monoaminergic compartment was associated with increased cortical excitability ( r = 0.29, P = 0.02). By contrast, ^[18F] THK5351 PET signal in the hippocampal formation, although strongly correlated with brainstem signal in whole-brain voxel-based quantification analyses ( P value corrected for family-wise error [ P _{FWE-corrected} ] < 0.001), was not significantly associated with cortical excitability ( r = 0.14, P = 0.25). Importantly, no significant association was found between early Aβ cortical deposits and cortical excitability ( r = –0.20, P = 0.11). CONCLUSION: These findings reveal potential brain substrates for increased cortical excitability in preclinical AD and may constitute functional in vivo correlates of early brainstem tau accumulation and neuroinflammation in humans. TRIAL REGISTRATION: EudraCT 2016-001436-35. FUNDING: F.R.S.-FNRS Belgium, Wallonie-Bruxelles International, ULiège, Fondation Simone et Pierre Clerdent, European Regional Development Fund.