Adolescence involves pronounced changes in sleep timing and duration that have been linked to executive functioning, impulsivity, and risk behaviors, yet evidence for generalizable sleep - self-regulation associations remains limited. We used regularized canonical correlation analysis to examine multivariate relationships between sleep and self-regulation across two independent cohorts. In the Adolescent Brain Cognitive Development study (n = 11,143), later chronotype and shorter sleep duration were associated with higher impulsivity, particularly urgency and deficits in planning and perseverance (r = 0.21, permutation p < 0.001), with minimal contribution from delay discounting. Social jetlag showed weak loadings. In the National Consortium on Alcohol and Neurodevelopment in Adolescence cohort (n = 831), only one canonical function was statistically significant (r = 0.15, p = 0.011), characterized by later chronotype and greater social jetlag, with minimal contribution from sleep duration and primary loadings on impulsivity-related measures. Applying the ABCD-derived sleep - self-regulation pattern to NCANDA produced a small but nonzero association, driven primarily by social jetlag and delayed sleep timing, with minimal influence of sleep duration. These findings provide multivariate evidence linking delayed sleep timing and circadian misalignment to adolescent self-regulation, though effect sizes attenuate across cohorts. Longitudinal work is needed to clarify predictive pathways and inform sleep-focused interventions during this vulnerable developmental period.

ABSTRACT Postnatal maternal depression has been associated with changes in infant sleep/wake cycles, but the literature presents inconsistent results, especially when different assessment methods are used. This study investigated the association between postnatal maternal depressive symptoms and rest-activity rhythms in early childhood. Data from 179 mother-infant dyads were analysed, with maternal depressive symptoms assessed with the EPDS at postpartum and with the PHQ-9 when infants were six months of age, and infants` rest-activity rhythms measured through actigraphy using nonparametric variables (L5, M10 and RA). Multiple linear regression models were estimated, adjusting for infant sex, maternal age, socioeconomic level, maternal race/ethnicity, and gestational age. No statistically significant associations were found between both maternal depressive symptom scores and infant rest-activity rhythm variables after adjustment for covariates. These findings are consistent with studies suggesting that maternal depression may affect the perception of infant sleep more than its objective quality, reinforcing the importance of objective measures and the need for longitudinal studies using combined methods.

This hypothesis-driven study tested whether circadian amplitudes of wrist temperature (WTA), physical activity (PAA), and light exposure measured by actigraphy predicted morning leptin in 64 Arctic residents, and whether the CLOCK 3111 polymorphism (rs1801260) modulated these predictions. Actigraphy measures (circadian amplitudes of WT, PA, and light exposure) and morning leptin concentrations were assessed across seasons with contrasting photoperiods. Multivariate regression models identified leptin predictors. Post-hoc analyses examined WTA-leptin relationships, considering CLOCK 3111 genotype and an exploratory leptin threshold of 13 ng/mL. A multivariate analysis adjusted for the photoperiod revealed significant negative associations between leptin and WTA (β = -0.344), PAA (β = -0.323) and sleep efficiency (β = -0.265) that were retained after further adjustment for age, sex and indigeneity. In the fully adjusted model, a larger normalized amplitude of blue light exposure (NA BLE) was associated with increased WTA (β = 0.256) and lower leptin (β = -0.171). The CLOCK 3111 polymorphism modulated the WTA - leptin relationship, with a strong negative correlation in TT individuals (r = -0.509) and a non-significant trend towards a positive association in CC individuals (r = 0.282), Δr = 0.791, z = 2.31, p = 0.021. In CLOCK 3111 TT individuals, those with a WTA <1°C had significantly higher odds (OR = 3.93, 95% CI: 1.69-9.17, p = 0.0015) and increased relative risk (RR = 2.70, 95% CI: 1.47-4.99, p = 0.0014) of having a morning leptin ≥13 ng/mL, compared to those with a WTA >1.5°C. Overall, the smaller circadian amplitude of WTA and PAA, the lesser sleep quality, and the smaller normalized amplitude of blue light exposure (NA BLE), independently of photoperiod, are associated with elevated leptin in Arctic residents. The CLOCK 3111 polymorphism modulates the WTA-leptin relationship. For CLOCK 3111 TT individuals, a small WTA (<1°C) may identify those at risk of elevated morning leptin (≥13 ng/mL), informing metabolic risk assessment in unique environments.

ABSTRACT This cross-sectional study aimed to investigate the combined effects of chronotype, Mediterranean diet adherence, and sleep quality on mental distress in university students, and to identify key predictors through advanced statistical modelling and machine learning approaches. A total of 659 undergraduate students aged 18–30 y in Konya, Türkiye, participated in the study. Chronotype was assessed using the Morningness – Eveningness Questionnaire (MEQ), sleep quality with the Pittsburgh Sleep Quality Index (PSQI), Mediterranean diet adherence with the Mediterranean Diet Adherence Screener (MEDAS), and mental distress with the Food-Mood Questionnaire (FMQ). Pearson correlation analyses, hierarchical regression, and path analysis were conducted to examine associations and potential mediation pathways. Additionally, an explainable XGBoost model with Shapley Additive Explanations (SHAP) values was applied to identify the most influential predictors of mental distress. Poorer sleep quality and evening chronotype were significantly associated with higher mental distress. Morning chronotype was positively associated with MEDAS but not with Body Mass Index (BMI). Hierarchical regression indicated that PSQI was the strongest predictor of mental distress, followed by chronotype. Path analysis further revealed that sleep quality significantly mediated the relationship between chronotype and mental distress, whereas Mediterranean diet adherence did not show a mediating effect. The XGBoost model demonstrated robust predictive performance, and SHAP analysis confirmed chronotype and sleep quality as the most influential variables in predicting mental distress. Evening chronotype and poorer sleep quality were associated with higher levels of mental distress in university students, while dietary quality did not show a significant independent association with mental distress in this sample. These findings highlight the importance of interventions focusing on circadian alignment and sleep hygiene to support mental well-being in young adults.

ABSTRACT Young adulthood is a critical period for the development of metabolic disorders. Time-restricted feeding (TRF) has been proposed as an intermittent fasting strategy to mitigate these effects. However, its impact when feeding occurs out of sync with the biological clock remains uncertain. This study aimed to investigate the effects of mistimed time-restricted feeding during the light phase on metabolic and circadian outcomes in young female Wistar rats maintained on a pre-existing Western-diet background. Post-weaning rats (n = 24) were divided into a control group (standard chow diet) (C) and an western group (Western-style diet) (W) ad libitum for 8 weeks. The western group was further split into two subgroups: western ad libitum (WA) and western time-restricted (WR, 12-hour feeding window – light phase). Body weight, fat deposition, food intake, locomotor activity, glycemic and lipid profiles, hepatic lipid content, and circadian parameters were evaluated. At the end of the experimental period, Western-style diet exposure was associated with increased visceral adiposity and metabolic disturbances, consistent with a diet-induced obese phenotype. TRF during the light phase reduced visceral adiposity but paradoxically increased plasma glucose levels and relative liver weight, altered feeding patterns, disrupted glycemic rhythms, and reduced robustness of locomotor activity rhythms. Overall, these findings suggest that mistimed TRF may promote circadian misalignment and metabolic alterations under Western-diet conditions, highlighting a dissociation between metabolic and circadian responses.

ABSTRACT Night shift work is linked with cardiovascular disease (CVD), although underlying mechanisms remain unclear. Heart rate variability (HRV) is a well-established biomarker, but heart rate fragmentation (HRF) may offer additional insights. We conducted a study to compare heart rate metrics, including HRV and HRF, across different types of shift schedules, and to evaluate the influence of sleep duration. In this cross-sectional study, we included 845 participants (mean age 64; 51% women) from the Multi-Ethnic Study of Atherosclerosis Sleep study. Heart rate metrics were compared between the day shift (reference), night/rotating shift, and other shift workers using adjusted linear regression. HRV was measured from overnight bipolar (Electrocardiogram) ECG. HRV (log transformed) and HRF values were reported as % difference with 95% confidence intervals (CIs). Analyses were stratified by sleep duration (short <7 h, recommended 7-<9 h, and long ≥9 h), and tested for interaction. Night/rotating shift workers had higher HRF than day shift workers, particularly a greater percentage of normal-to-normal intervals in alternation segments (PAS) (% difference 11.9, 95% CI 1.8, 22.0). We found differences based on sleep duration for PAS. The difference was most pronounced in workers with short sleep (% difference 20.4, 95% CI 3.0 to 37.9), somewhat smaller in those with recommended sleep (% difference 14.2, 95% CI −1.0 to 29.5), and reversed in long sleepers (% difference −10.8, 95% CI −32.4 to 10.8; interaction p = 0.06) Interaction terms were assessed at p < 0.10. HRV metrics showed minimal differences and no consistent patterns across shift groups. Night shift work is related to higher HRF, and sleep duration influences these findings, which may reflect circadian misalignment and autonomic dysregulation.

ABSTRACT The current cross-sectional and observational online study investigated previously reported associations between chronotype, sleep duration, inattention traits, and self-esteem within one indirect-effect model in a general, mostly student, population. Chronotype was operationalized as a continuous μMCTQ-derived score, with higher values indicating later sleep timing and greater evening orientation. We found that chronotype and self-esteem were negatively related, with lower self-esteem observed in participants with later sleep timing. This association was statistically accounted for in part by reported inattention traits, irrespective of reported sleep duration. Participants with higher chronotype scores on average reported more inattention traits, and lower self-esteem. Age effects, found for chronotype score, sleep duration, and inattention traits, were controlled for. Because all variables were measured concurrently, these findings should not be interpreted as evidence that eveningness causes inattention or low self-esteem. Instead, they show that previously reported bivariate relationships are likely connected in the same correlational pattern. Longitudinal, experimental, or network approaches are needed to test temporal ordering, alternative explanations, and possible intervention targets.

ABSTRACT This cross-sectional study examined whether cumulative adverse social determinants of health (SDOH) were associated with accelerometer-derived rest-activity rhythms and multidimensional sleep metrics, and whether depression and overactive bladder statistically accounted for part of the SDOH-relative amplitude association in exploratory pathway analyses. We analyzed 6,130 U.S. adults aged 20–80 y (mean age 49.5 y; 51.7% female) from NHANES 2011–2014. From wrist-worn 7-d accelerometer recordings, nonparametric rest-activity indices (interdaily stability, intradaily variability, and relative amplitude) and sleep parameters (duration, efficiency, timing irregularity, social jetlag, and catch-up sleep) were derived. A composite SDOH score (0–8) was constructed across economic, educational, healthcare, housing, and social domains. In fully adjusted survey-weighted linear regression, each 1-unit higher SDOH score was associated with lower relative amplitude (beta = −0.007; 95% CI, −0.008 to −0.005), greater rhythm fragmentation, shorter sleep duration, lower sleep efficiency, and more irregular sleep timing. Graded associations were observed across SDOH quartiles. At the component level, unpartnered status, unemployment, and food insecurity showed the most consistent inverse associations with rhythm robustness. Exploratory pathway analyses were consistent with small indirect associations through depression severity and overactive bladder. Overall, greater cumulative adverse SDOH burden was associated with less robust, more fragmented rest-activity rhythms and poorer multidimensional sleep health.

ABSTRACT The light–dark cycle shaped by Earth’s 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°S), who wore wrist actigraphy continuously for 4 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 relevant component of human circadian temporal organisation.

ABSTRACT Conventional chemotherapy is limited by severe systemic toxicity, suboptimal pharmacokinetics, and nonspecific drug distribution. Chrono-modulated drug delivery systems (CDDS) address these challenges by aligning drug release with circadian rhythms, thereby enhancing efficacy and minimizing adverse effects. This strategy capitalizes on temporal fluctuations in drug metabolism, DNA repair mechanisms, cell proliferation, and immune function to refine pharmacokinetic and pharmacodynamic profiles. This review synthesizes recent preclinical and emerging clinical studies exploring chronomodulated chemotherapy, with a focus on delivery-system design and translational feasibility. Technological innovations, including stimuli-responsive hydrogels, nano- and micro-carriers, 3D printed formulations, and programmable infusion devices, enable precise temporal drug release. Comparative evaluation of these platforms reveals improved therapeutic indices and reduced toxicity, underscoring the clinical promise of chronotherapy in oncology. However, significant obstacles remain, including limited clinical standardization, regulatory barriers for drug-device combinations, formulation complexity, and inter-patient chronotype variability. Future integration of wearable biosensors, AI, and adaptive trials is expected to accelerate clinical translation. Overall, this review positions chronomodulated drug delivery as a strategically mature yet clinically underutilized approach for advancing precision oncology.