Journal of Biological Rhythms

Both active movement profiles and robust circadian rhythms are linked to improved health outcomes, yet the underlying mechanisms remain partially understood. We investigated this relationship in young adults (n = 169, aged 18-30 years) under real-world conditions using actigraphy data. We performed k-means clustering on 12 accelerometer-based features capturing magnitude, duration, frequency, and intensity distribution to derive movement behavior profiles. As a proxy of circadian rhythms integrity we computed the Circadian Function Index (CFI), which combines intradaily variability, interdaily stability, and relative amplitude. We also assessed circadian phase and sleep quality parameters. Additionally, we quantified light exposure and physical activity over 3-hour daily intervals. The unsupervised algorithm identified two non-overlapping profiles among participants, the More Active (MA) and the Less Active (LA) profiles. MA exhibited a higher CFI (0.81 {+/-} 0.06 vs. 0.69 {+/-} 0.06, p <0.001), which was also positively associated with early-evening physical activity, but not with light exposure. MA also showed an earlier circadian phase, estimated as the midpoint of the five least active hours (L5c, 04:30 {+/-} 01:03 vs. 04:59 {+/-} 01:15, p adj. = 0.04), which was inversely associated with early-morning physical activity and late-morning light exposure. We found no differences in sleep quality between MA and LA. Our results underscore the association between movement behavior and overall circadian rhythms integrity. Importantly, these findings reinforce actigraphy as a multidimensional tool for both health research and clinical applications.

Historically, the primary method for measuring murine circadian activity in vivo has been monitoring voluntary wheel running. Recently, passive infrared (PIR) motion sensors have emerged as an alternative that is not reliant on voluntary behaviour. While research has examined the differences between the two methods for measuring circadian parameters, little focus has been placed on how these techniques may confound the assessment of therapeutic interventions. Here, we show that wheel running activity is disproportionately affected by daily oral gavage of saline compared to sham gavage treatment. In contrast, PIR-monitored activity indicates little difference between the two treatments. Both PIR and running-wheel-measured activity show a reduction in circadian amplitude and an increase in intradaily variability during both types of gavage, likely reflecting the stress of daily gavage, though the mice showed no weight loss. This finding indicates that pre- and post-intervention comparisons will misattribute gavage effects to the intervention unless appropriate sham and vehicle controls are included. More broadly, the choice of circadian measurement technique fundamentally shapes the interpretation of pharmacological interventions and must be considered in experimental design.

BackgroundMood symptoms vary seasonally, yet the underlying mechanisms remain unclear. We tested whether wearable-derived sleep, activity, circadian, and light exposure patterns mediate seasonal effects on mood in youth with emerging mood disorders. MethodsWe analysed 733 observation periods from 422 Australian youth (mean age 24.3{+/-}5.5 years; 63% female) attending early-intervention mental health services. Each observation comprised a clinical assessment paired with [&ge;]5 valid days of GENEActiv wrist actigraphy. Season was modelled using sine-cosine functions of day-of-year. Sleep, activity, and circadian features were reduced using Joint and Individual Variation Explained, and light exposure features were reduced via principal components analysis. Linear mixed-effects models tested seasonal effects on depressive, psychiatric, manic, and functional outcomes. Mediation was examined using Sobel screening followed by cluster bootstrapping (1,000 iterations). ResultsDepressive ({beta}=-0.67, p=0.023) and negative symptoms ({beta}=-0.17, p=0.041) peaked in winter, whereas manic symptoms peaked in autumn ({beta}=0.24, p=0.018). Reduced day-to-day variability in moderate-to-bright ambient light exposure (fewer transitions to brighter environments) mediated winter increases in depressive (indirect {beta}=-0.06, p=0.006) and negative symptoms (indirect {beta}=-0.05, p<0.001). Higher activity levels partially mediated seasons effect on depressive symptoms (indirect {beta}=-0.010, p=0.032). Extended sleep with nocturnal activity mediated seasons effect on negative symptoms (indirect {beta}=-0.02, p=0.001). No mediators emerged for manic symptoms. ConclusionsLight exposure variability--reflecting constrained engagement with brighter environments during winter--emerged as the dominant mediator of seasonal mood worsening in Australian youth, with smaller contributions from sleep-activity-circadian patterns. These findings identify daily light variability as a promising, modifiable target for intervention.

2)BackgroundCircadian rhythm desynchrony (CD) occurs when there is a mismatch between the circadian clock and local time, such as shift work. Mouse models are commonly employed to study CD, but may have significant shortcomings such as environmental masking, a focus only on sleep physiology, and significant variability between study designs. ObjectiveThis study used in vivo telemetry for simultaneous, real-time monitoring of locomotor activity (LA), core body temperature (CBT), and brain activity (EEG) in freely moving C57BL/6J mice to assess CD effects. MethodsFour-month-old C57BL/6J mice (n=11) were surgically implanted with telemeters enabling simultaneous real-time recording of LA, CBT, EEG.: Mice were sequentially exposed to a control condition standard 12:12h light-dark cycle (T24) then 4, 8-day CD paradigms: 10:10 h short day (T20), social jet lag (SJL), repeated 6h phase advances (6A2), and a 3:3 h ultradian cycle (T6)For each paradigm, the final 48h of data (250 Hz) were analyzed. ResultsWe found clear differences in the severity of the effects of each CD paradigm on sleep and circadian fitness, where T20[~]T6>SJL>6A2. CBT revealed broader disruption, but EEG outputs proved the most sensitive indicators of internal desynchrony. ConclusionsEach CD paradigm produced a unique profile across behavioral, physiological, and neural domains. We have also identified Gamma CV as a novel, sensitive metric of CD. These results highlight the necessity of multimodal monitoring to accurately characterize the impact of ecologically relevant stressors on circadian and sleep physiology. Statement of SignificanceCircadian rhythm desynchrony (CD), driven by shift work, jet lag, and modern irregular light exposure, is a major health burden linked to metabolic, neurodegenerative, and neuropsychiatric diseases. However, standard methods for measuring CD in laboratory models often rely on simple locomotor activity, which can "mask" the true extent of internal circadian stress. In this study, we simultaneously monitored brain EEG activity, core body temperature, and motion across four distinct models of circadian stress. We discovered that locomotor activity is a deceptive indicator of health; while mice appeared to show no alterations under several stress paradigms, their brain waves and body temperatures revealed the underlying impact of CD. Specifically, we identified "Gamma CV" as a highly sensitive new brain-wave marker that detects early circuit instability even when behavior appears normal and sleep quantity is preserved. These findings provide a marker for identifying early neurological vulnerability to irregular light schedules, offering a potential bridge to understanding similar gamma brain-wave alterations seen in addiction, early-stage Alzheimers disease, and other disorders.

We examined the overlap in the genes associated with daily rhythms and with behavioral plasticity in ants. We first investigated the daily rhythms of gene expression in the harvester ant, Pogonomyrmex barbatus, and how the rhythmic genes overlap with others previously shown to be associated with plasticity of foraging behavior. Then, to consider whether the overlap is conserved across ant species, we compared rhythms of gene expression in the diurnal, desert harvester ants with those previously reported for a distantly related nocturnal, subtropical carpenter ant, Camponotus floridanus. First, daily transcriptomes in P. barbatus showed that most genes were expressed in light-dark (LD) and constantly dark (DD) conditions at about the same levels; only 11 genes showed at least a two-fold change in expression. Network analysis identified eleven modules of P. barbatus genes under LD conditions. Of these 11 clusters, modules C1 and C2 seem to be central nodes of the gene expression network, because they are the most highly connected in LD, and show the strongest preservation in DD vs. LD, and contain core clock gene Period. Only one module, C2, showed significant overlap with P. barbatus genes that have 24h-rhythmic expression in both LD and DD. There was significant overlap between modules C1, C2, C10, C11, and P. barbatus genes found previously to be associated with plasticity in the regulation of foraging activity to manage water loss. A comparison of the daily transcriptome of P. barbatus with that of C. floridanus showed significant overlap of 24h-rhythmic genes in LD. Modules C1 and C2 of P. barbatus also overlap with C. floridanus genes previously shown to differ in expression rhythms in nurses and foragers. In combination, these results indicate that genes linking plasticity of the circadian clock and of behavior may be broadly conserved in ants.

Actigraphy is a non-invasive and cost-effective method for monitoring behavioral rhythms under real-world conditions by collecting time-resolved measurements of locomotor activity, light exposure, and temperature. Although several open-source packages support specific aspects of actigraphy analysis, aspects such as preprocessing, metric calculation, and mathematical modeling are often distributed across separate software packages, limiting interoperability and increasing programming overhead. Here we introduce circStudio, a Python package that unifies actigraphy data processing and mathematical modeling of circadian rhythms within a single framework. Built from the pyActigraphy codebase and integrating circadian models from the Arcascope circadian package, circStudio provides flexible preprocessing tools, support for multiple actigraphy file formats through adaptor classes, standalone functions for computing commonly used actigraphy metrics, and implementations of several mathematical models of circadian rhythms. The package enables users to move efficiently from raw wearable data to physiologically interpretable circadian outputs. Ultimately, circStudio aims to facilitate reproducible workflows and to provide a flexible foundation for research applications across circadian biology, sleep science, and digital health.

Sleep-wake regulation arises from the interaction between homeostatic sleep pressure and circadian timing, yet current assessments evaluate these processes independently and fail to capture their dynamic modulation by environmental pressures. This limitation is particularly relevant in adolescents with attention-deficit/hyperactivity disorder (ADHD), who are at increased risk of circadian delay and sleep disruption. Here, we combined month-long wearable-based physiological monitoring with ecological behavioral assessments in adolescents with ADHD to characterize circadian and homeostatic processes dynamically in real-world settings. Using continuous skin temperature recordings, we derived individualized and day-specific estimates of circadian phase through hierarchical modelling, and integrated these measures with actigraphy-based sleep estimates and daily assessments of neurocognitive functioning and functional impairment. Temperature-derived circadian phase correlated with questionnaire-based chronotype but more accurately predicted sleep patterns. Delayed circadian phase was associated with later sleep onset and greater weekday-weekend variability. Importantly, circadian phase exhibited significant day-to-day fluctuations, particularly in individuals with delayed phase, reflecting interactions with environmental constraints. Sleep latency was jointly determined by homeostatic sleep pressure and day-specific circadian phase, with combined models outperforming either process alone. Crucially, both sleep deprivation and day-specific circadian misalignment independently predicted fluctuations in ADHD symptom severity, perceived stress, and neurocognitive impulsivity. In contrast, mean circadian phase alone did not explain behavioral variability. These findings demonstrate that circadian regulation is a dynamic, environmentally sensitive process rather than a fixed trait. Wearable-based estimation of circadian phase provides a scalable approach to capture these dynamics and may enable personalized interventions targeting sleep and circadian dysregulation.

The Drosophila adult central brain contains 240 circadian neurons, of which there are more than 25 different neuron subtypes based on connectomic data. Recent single cell RNA-seq (scRNAseq) characterization of these neurons "around the clock" also indicates a similar number of molecular subtypes of circadian neurons, but other conclusions from these transcriptomic studies warranted verifying and extending with other approaches. To this end: 1) We used a genetic multiplexing strategy to profile the transcriptomes of circadian neurons from multiple time points in a single experiment, reducing confounding technical variation between timepoints; 2) Large numbers of single nuclei were sequenced (snRNA-seq), which was enabled because the new method EL-INTACT purifies nuclei from frozen heads; 3) We assayed 12 time points under both light-dark (LD) and constant darkness (DD) conditions. These approaches showed dramatic transcriptional differences between time points in many circadian neuron types and enhanced time-of-day gene expression analysis. The data indicate that most of this regulation is transcriptional and circadian. There were however a small number of light-dependent transcripts, including a few that correspond to mammalian immediate-early genes. They probably play a role in the light-regulation of gene expression and behavior in specific neurons, perhaps circadian entrainment or phase-shifting. The results taken together provide a more comprehensive picture of gene expression heterogeneity within adult Drosophila circadian neurons including how intrinsic clock mechanisms and light cues are integrated across circadian neuron subtypes.

Abstract Background: While total physical activity is a recognized modifier of cancer risk, accelerometer-derived digital phenotyping enables high-resolution mapping of circadian behavior. Whether these multidimensional patterns comprising step counts, sleep, physical activity, circadian rhythmicity, and light exposure independently influence the risk of incident colorectal cancer (CRC) has not been comprehensively evaluated Methods: We performed an exposure-wide association study (ExWAS) of 224 accelerometer-derived metrics among 95,050 UK Biobank participants who were free of CRC at accelerometry. To comprehensively define circadian rhythm patterns, we systematically categorized these metrics into five core behavioral domains: step counts, sleep architecture, physical activity bouts, circadian rhythmicity, and light exposure. Hazard ratios (HRs) and 95% confidence intervals were estimated using Cox proportional hazards models with age as the underlying timescale. Results: During a median follow-up of 8.5 years, 775 participants developed CRC (503 colon; 269 rectal). In minimally adjusted models, 121 metrics showed nominal significance (31 for overall CRC, 89 for colon, and 1 for rectal cancer). Protective associations were predominantly observed for metrics characterizing activity intensity and bout structure; notably, higher mean acceleration during 5-10 minute bouts of moderate-to vigorous physical activity was associated with reduced CRC risk (HR 0.88 per SD). In contrast, no metrics within the defined sleep or light exposure domains reached nominal significance. These associations attenuated substantially following progressive adjustment for lifestyle and metabolic covariates, suggesting potential confounding or shared biological pathways. Conclusions: Our findings identified specific behavioral phenotypes within a multidimensional framework of circadian rhythm, including step counts, physical activity intensity, and bout structure, as being associated with CRC risk. However, the marked attenuation of signals after multivariable adjustment suggests these markers may not serve as independent predictors. These results underscore the complexity of multidimensional circadian digital biomarkers and necessitate independent replication to clarify their utility in cancer risk stratification.

The light-dark cycle shaped by Earths rotation provided the evolutionary conditions under which circadian rhythms emerged. Consistent with this, previous studies indicate that less than 40% of total blind individuals, who lack photic input, entrain to the 24-h cycle, further evidencing the critical role of light as the dominant zeitgeber for circadian alignment. However, this assumption has been tested almost exclusively in temperate, high-latitude regions, where environmental cues vary seasonally. Near the equator, by contrast, photoperiod and temperature cycles remain exceptionally stable. This highlights a fundamental gap: can circadian rhythms in humans remain synchronised without light when environmental temporal cues are highly regular? We addressed this question in 58 blind adults (21-77 years; 43.1% female) living near the equator in Rio Grande do Norte, Brazil ([~]5{degrees}S), who wore wrist actigraphy continuously for four weeks. Light sensitivity was assessed through the pupillary light reflex (PLR; 22 PLR-reactive, 36 non-reactive). Applying a semi-supervised machine learning approach to uncover multidimensional patterns without prior categorisation, we identified two distinct phenotypes: a Higher Circadian Stability (HCS; 72%, n = 42) and a Lower Circadian Stability group (LCS; 28%, n = 16). Notably, 64% of PLR-non-reactive individuals (23 of 36) were classified within the HCS group, a proportion approximately 1.6 times higher than previously reported for blind cohorts. These findings demonstrate that, under exceptionally regular equatorial conditions, non-photic cues can sustain a robust circadian entrainment even in the absence of photic input. We propose that environmental regularity promotes the synergy of non-photic timing signals, underscoring ecological context as a key determinant of human circadian temporal organisation.

BackgroundLight plays a critical role in mental health, as the primary input to the circadian system, which regulates mood, energy, and the sleep-wake cycle. Altered light sensitivity is a potential mechanism in circadian-associated mental disorders. MethodsActigraphy-derived sleep, physical activity, and circadian rhythm correlates of the pupillary light reflex were explored in young people with emerging mental disorders. Participants were 27 healthy controls (Mean age=25.67 {+/-} 2.83, 52% female) and 155 young people from the Neurobiology Youth Follow-up Study (Mean age=25.48 {+/-} 5.65; 60% female), recruited from an early intervention mental health service. 32% of the latter group were re-assessed over 12 months. Pupil constriction, average and maximal constriction velocity, and constriction latency were recorded by the PLR-3000 monocular pupillometer in response to dim (~10 lux) and bright (~1500 lux) pulses. ResultsCompared to healthy controls, young people with emerging mental disorders had a smaller change in pupil diameter (p=0.037) and a slower maximal constriction velocity (p=0.018) in response to dim light. In the full sample, decreased dim light sensitivity was correlated with later timing of actigraphy-derived sleep midpoint. Within the clinical cases, increased genetic risk for bipolar disorder was correlated with increased dim light sensitivity, and higher insomnia clinical scores were correlated with decreased dim light sensitivity. Pupillometry measures were stable across time and seasons. ConclusionAltered light sensitivity may be associated with the emergence of mood disorder in young people and with altered sleep-wake timing.

Circadian clocks coordinate physiological and behavioral rhythms by synchronizing biological processes with environmental cues. These rhythms emerge during development, but it remains unclear whether their component genes are activated by a common program or assembled through distinct regulatory pathways. To address this, we used longitudinal luciferase reporters to monitor per3 and per2 expression across zebrafish embryonic and larval development. Although both genes are canonical components of the circadian clock, they showed strikingly different developmental regulation. Two temporal frames of circadian gene expression were identified: an embryonic stage and a larval stage, each evident under different entrainment conditions. Per3 displayed early rhythmic expression in light/dark conditions, which was independent of per2 and cry1a light-entrainment regulation, but required bmal activity. Meanwhile, per2 displayed light-responsive transcription and remained largely bmal-independent. At the same time, both genes exhibited an endogenous embryonic expression that could not be explained solely by light-driven regulation, indicating that developmental inputs contribute to clock gene activation before mature larval rhythms are established. These findings demonstrate that the zebrafish circadian system is not assembled through a single synchronized onset of clock gene expression, but through gene-specific regulatory programs that shift across development.

Food anticipatory activity (FAA) is a robust behavioral output of food-entrained circadian rhythms, characterized by increased locomotor activity prior to scheduled feeding. Despite the social nature of rodents, FAA is almost exclusively studied in singly housed animals, leaving the influence of social context largely unexplored. Here, we used implanted wireless devices to measure individual locomotor activity and subcutaneous body temperature in group-housed mice and compared these measures to singly housed controls. Social housing significantly suppressed FAA in both male and female mice. In parallel, preprandial increases in body temperature were markedly attenuated in group-housed animals. These findings demonstrate that FAA is a flexible, state-dependent behavior that reflects both circadian timing and energetic demand. Together, these results identify social context as an important and underappreciated determinant of food-entrained circadian biology.

Actigraphy is a popular behavioral sleep assessment tool in research and clinical practice. Hierarchical hand-scoring approaches remain the standard for actigraphy rest interval estimation, but can be impractical for large cohort studies and suffer from reproducibility problems. We developed a semi-automated pipeline (actiSleep) to set rest intervals consistent with best-practice hand-scoring algorithms incorporating event marker, diary, light, and activity data. To evaluate actiSleep performance, we used data from an observational study of 51 adolescents (14-19yr), with and without family history of bipolar disorder. Participants completed 2 weeks of wrist actigraphy and daily sleep diary. We first hand-scored records using a standardized hierarchical algorithm incorporating event marker, diary, light, and activity data. We then compared the hand-scored rest intervals to those from actiSleep and two automated activity-based algorithms ( Activity-Merged, Activity-Only). Activity-Only used activity-based sleep estimation and Activity-Merged joined closely adjacent rest intervals. For rest onset, rest offset, and rest duration, all algorithms had strong mean agreement with hand-scoring: actiSleep estimates were within 1-3 minutes, Activity-Merged within 2-4 minutes, and Activity-Only within 7-14 minutes. However, actiSleep had notably better (narrower) margins of agreement with hand-scoring, as evidenced by Bland-Altman plots, and greater positive predictive value and true positive rates for rest detection, especially in the 60 minutes surrounding the onset and offset of the rest interval. The actiSleep algorithm successfully estimates actigraphy rest intervals comparable to hand-scoring while avoiding pitfalls of activity-only algorithms. actiSleep has potential to replace hand-scoring for research in adolescents but requires further testing and validation in other samples.

Objectives: Self-applied, low-density EEG offers opportunities to examine sleep in the home environment, yet its feasibility during behavioural sleep interventions remains unexplored. This pilot study aimed to evaluate the feasibility and acceptability of a self-applied, low-density EEG device during sleep restriction therapy (SRT) and explore effects on sleep and affect. Methods: Seventeen adults with insomnia and depressive symptoms completed a 2-week baseline and 4 weeks of SRT. The primary outcome was the proportion of expected EEG recordings completed and scoreable. Secondary outcomes included clinical measures, sleep continuity (sleep diary, actigraphy), sleep architecture (low-density EEG for 9 nights), power spectral density, and affect. Data were analysed with linear mixed models. Cohen's d and 95% confidence intervals were reported. Results: Feasibility was demonstrated (92% of expected EEG nights completed). SRT was associated with reductions in insomnia severity, depressive symptoms, negative affect, and increases in positive affect. Robust improvements were observed across treatment in sleep continuity (SOL, WASO, SE) from diary, which were paralleled by actigraphy. EEG revealed reduced TIB, TST, N1, N2, REM sleep, and REM latency during week one. Reductions in EEG-derived TIB and N1 sleep were maintained at night 28. There were no reliable differences for spectral or spindle measures. Conclusions: These findings suggest that self-applied, low-density EEG during SRT is feasible, acceptable, and may capture sleep changes during treatment. They highlight the potential for multi-night monitoring of sleep interventions at home and elucidating mechanisms underlying therapeutic change.

Mice housed at room temperature (RT, 25{degrees}C) experience chronic mild cold stress compared with those housed at thermoneutrality (TN, 30{degrees}C). We hypothesized that cold stress suppresses circadian transcript expression in peripheral tissues. RNA-seq of hearts, livers, and diaphragms collected every 4 hours over 48 hours in constant darkness identified mRNA transcripts exhibiting {approx}24-hour rhythms (REGs). TN produced tissue-specific changes in REG number, identity, and phase without altering core circadian clock transcript levels. Cardiac REGs increased 4-fold, diaphragm REGs 1.5-fold, and hepatic REG identity shifted substantially. GO analysis revealed coordinated reorganization of rhythmic metabolic programs in the heart and liver. These data demonstrate that ambient housing temperature has tissue-specific effects on the number, identity, and temporal organization of rhythmically expressed transcripts in the heart, liver, and diaphragm.

BackgroundAutistic individuals experience higher rates of sleep problems throughout their lives, and there is considerable heterogeneity in manifestations of these issues that remains unexplained. Here, we examine associations over time of heterogenous sleep trajectories with autism diagnosis, and behavioural and genetic factors related to autism. MethodWe used data from the Avon Longitudinal Study of Parents and Children (N=13,886, autistic n=150). The primary outcome was parent and self-reported night-time sleep duration, measured on 10 occasions (between 0.5y and 15.5y). The independent variables were autism diagnosis, autism polygenic score (PGS) and four parent-reported autistic traits: repetitive behaviour, social communication, speech coherence, and sociability. Latent class growth analysis was conducted to identify heterogenous classes of sleep trajectories, and these trajectory classes were regressed onto the independent variables. ResultsFour night-time sleep duration trajectory subclasses were identified; shorter (n=512, 4.1%), longer (n=1654, 13.1%), intermediate-shorter (n=3630, 28.8%), and intermediate-longer (used as the reference class; n=6825, 54.1%). An autism diagnosis was associated with a shorter or intermediate-shorter sleep duration trajectory, compared to the reference class. Similarly, higher scores in domains of repetitive behaviour, speech coherence and social communication were associated with shorter sleep duration trajectories. The autism PGS and sociability were not associated with any sleep trajectories compared to the intermediate-longer sleep trajectory (reference group). ConclusionAn autism diagnosis and specific autistic traits were associated with poorer long-term sleep outcomes across childhood and adolescence, highlighting the need for early, sustained sleep interventions, and the potential of trait-specific mechanisms for sleep problems. HighlightsO_LIFour distinct night-time sleep duration trajectories were identified across development C_LIO_LIAutism diagnosis predicted shorter and intermediate-shorter sleep trajectories C_LIO_LISpecific (but not all) autistic traits were linked to shorter sleep trajectories C_LIO_LIAutism PGS did not predict sleep duration trajectories C_LI

Background: Circadian rest-activity rhythms weaken with age, but whether sleep disorders modify this trajectory is unknown. Methods: We analyzed wrist accelerometry data from 4,386 participants aged 6-80 years in the 2011-2012 National Health and Nutrition Examination Survey (NHANES). Circadian features were extracted using cosinor analysis and nonparametric methods; a Circadian Disruption Index (CDI) was constructed from five standardized components. Survey-weighted regression with natural cubic splines and Wald F-tests tested age-by-sleep-disorder interactions using Taylor series linearization for variance estimation. Results: Doctor-diagnosed sleep disorder (N = 360, 8.2%) was associated with significantly different age-related trajectories of amplitude (F(2,17) = 11.24, p = 0.0008) and MESOR (F(2,17) = 8.22, p = 0.0032), both surviving Bonferroni correction (p < 0.006). CDI was higher in those with a sleep disorder (0.290 vs. 0.131, p < 0.001) and was independently associated with higher BMI (beta = 1.33 kg/m2, p < 0.001), higher HbA1c (beta = 0.089%, p = 0.004), greater diabetes prevalence (beta = 3.8 percentage points, p < 0.001), and worse depressive symptoms (beta = 0.43 PHQ-9 points, p = 0.020). Sensitivity analyses using a broader sleep problem exposure did not replicate these interactions. Conclusions: Doctor-diagnosed sleep disorders are associated with an altered age-related decline in circadian amplitude and mean activity level. CDI was independently linked to cardiometabolic and depressive outcomes, supporting a mechanistic connection between clinically significant sleep pathology and circadian disruption across the lifespan.

BackgroundThe mechanisms underpinning associations between sleep and psychiatric conditions are poorly understood, partly due to challenges with longitudinal sleep studies outside the laboratory. Children and young people with rare genetic conditions caused by micro-deletions or -duplications (Copy Number Variants or CNVs) have increased risk of disrupted sleep and poorer neurodevelopmental (ND) outcomes. The Sleep Detectives study aims to investigate this by tracking behavioural and neurophysiological signatures of sleep health in young people with ND risk or ND-CNVs. To optimally achieve this, we have worked with families with ND-CNVs and charity partners to co-design our tools, methods, study protocol, and materials. MethodWe established a Lived Experience Advisory Group (LEAP) with nine parents and 13 children and young people with ND-CNVs, alongside representatives of UK charities Max Appeal and Unique. Together, the research team and LEAP co-designed two in-person family workshops in which we collected feedback on the acceptability of sleep monitoring devices, the design of bespoke cognitive tasks, and overall study protocol. Informal interviews and surveys were conducted with LEAP members and researchers, to enable the team to reflect and learn from their Patient/Public Involvement (PPI) experiences. ResultsKey outputs included pre-workshop invitation and briefing materials and insights that iteratively refined the main study design, including the need for flexibility to increase accessibility, selection of sleep devices, customisation of cognitive tasks, and choice of language in documents. The PPI process was highly valued by LEAP members, workshop attendees, and the research team. One investigator described the PPI work as "reinvigorating my love of research by helping me focus on science that matters". Participating families also established peer support networks. ConclusionsInvolving families affected by ND-CNVs in co-designing the Sleep Detectives study maximised opportunities for acceptability, accessibility and scalability. The research team gained inspiration and deeper understanding of the impact of ND-CNVs on families. Families gained awareness about research, established connections with each other and peer support, and were enthusiastic about future research involvement. This experience empowered families to engage more deeply with the research process and helped the PPI work to be more impactful and inclusive. Plain English summaryChildren and young people with rare genetic conditions caused by small deletion or duplication of genetic material are more likely to experience sleep difficulties such as insomnia, restless sleep, and tiredness. They also show an increased likelihood of neurodevelopmental conditions such as learning disability and autism, and mental health issues such as anxiety. The Sleep Detectives team wanted to explore how these genetic conditions affect childrens sleep, cognition and psychiatric health. To make sure that the project design was well suited to the children and young people that would be invited to participate, the team worked closely with families to design the study. Parents and caregivers of affected children and young people were invited to join a Lived Experience Advisory Panel (LEAP), together with charity representatives and Sleep Detective researchers, to co-design two hands-on workshops, and advise on study design. Children and young people and parents/caregivers attending the workshops tried out and provided feedback on tools and devices that the research team were developing. They also advised on the arrangements and support families might need whilst taking part, and on the study protocol. This collaborative approach helped ensure the study design was optimally suited for the recruitment and participation of children and young people and their families. This report documents our public involvement work for the Sleep Detectives study, illustrating the difference the partnership between researchers and families has made to the project, and the wider benefits for all concerned.

Spending time in locations outside the home and workplace (termed "third places"), has been linked to better mental health. However, studies to date have typically been cross-sectional, based on self-reported location data and employed small sample sizes, limiting their ability to assess the presence and nature of the association between third places and mental health. To overcome these limitations, we collected 18,795 person-days of objective SensorKit location data passively from a national cohort of 410 first-year medical residents across the United States, to assess visits to third places and their associations with mood and depression over the course of one year. On average, participants visited 3.3 unique locations per day (SD=1.7) and spent 17.9% of their time at third places (SD = 26.5%). Within individuals, both a higher percentage of time spent at third places (B=0.013 [per 10% increase], p<0.001) and a greater number of unique locations visited (B=0.032, p<0.001) were associated with better mood later that same day, independent of the time spent at work. These associations were partially mediated by step counts and outdoor light exposure jointly (19.2% and 27.6%). Reverse-direction associations were observed, with better mood on one day predicting both more time spent at third places (B=0.052, p<0.001) and more unique locations visited (B=0.032, p<0.001) the following day. Between subjects, depressed subjects spent less percentage of time at third places (12.3% vs. 21.2%, t=-3.7, p<0.001) and visited fewer unique places per day (2.9 vs. 3.4, t = -3.8, p<0.001) compared to non-depressed subjects. These findings demonstrate the relationship between visiting third places and well-being, and suggest that interventions and policies aimed at encouraging third places visits have the potential to improve mental health.