Dissecting and modeling photic and melanopsin effects to predict sleep disturbances induced by irregular light exposure in mice.

Artificial lighting, day-length changes, shift work, and transmeridian travel all lead to sleep-wake disturbances. The nychthemeral sleep-wake cycle (SWc) is known to be controlled by output from the central circadian clock in the suprachiasmatic nuclei (SCN), which is entrained to the light-dark cycle. Additionally, via intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (Opn4), short-term light-dark alternations exert direct and acute influences on sleep and waking. However, the extent to which longer exposures typically experienced across the 24-h day exert such an effect has never been clarified or quantified, as disentangling sustained direct light effects (SDLE) from circadian effects is difficult. Recording sleep in mice lacking a circadian pacemaker, either through transgenesis (Syt10cre/creBmal1fl/- ) or SCN lesioning and/or melanopsin-based phototransduction (Opn4-/- ), we uncovered, contrary to prevailing assumptions, that the contribution of SDLE is as important as circadian-driven input in determining SWc amplitude. Specifically, SDLE were primarily mediated (>80%) through melanopsin, of which half were then relayed through the SCN, revealing an ancillary purpose for this structure, independent of its clock function in organizing SWc. Based on these findings, we designed a model to estimate the effect of atypical light-dark cycles on SWc. This model predicted SWc amplitude in mice exposed to simulated transequatorial or transmeridian paradigms. Taken together, we demonstrate this SDLE is a crucial mechanism influencing behavior on par with the circadian system. In a broader context, these findings mandate considering SDLE, in addition to circadian drive, for coping with health consequences of atypical light exposure in our society.

Hypnotic prescription by GPs is associated with their personal drug consumption but not by their insomnia status.

French general practitioners (GPs) are known to widely prescribe medications to treat insomnia despite their negative effects. GPs' easy access to self-medication may affect their mental representation of sleep and hypnotics, and subsequently their professional behaviour. Our aim was to examine the association between GPs' personal hypnotic drug consumption habits and their management of patients with sleep disturbances. A randomized sample of Alsatian GPs participated in a survey based on questionnaires including the Pittsburgh Sleep Quality Index, the Dysfunctional Beliefs About Sleep in 10 questions to characterize sleep, and an evaluation of their management strategies regarding sleep for both patients and themselves. Two-hundred and forty-nine GPs were included (response rate of 51%). Demographics of the GPs' samples were representative of those of the Alsatian GP population. Fifteen percent of the survey respondents met insomnia criteria. For the management of their own sleep disturbances, 14.3% of GPs were taking hypnotic drugs and 8.7% were taking anxiolytics, with greater drug consumption in the insomnia group. In a multivariate analysis, GPs who personally consumed these medications prescribed significantly more of them to patients, whereas their insomnia status had less impact. Other factors such as gender and type of practice were not associated with a higher prescription rate. Our results indicate that GPs' personal drug consumption can have a significant impact on the management of their patients, therefore suggesting that actions towards GPs' health improvement may also benefit their patients and the public.

Eveningness is associated with coronary artery calcification in a middle-aged Swedish population.

Coronary artery calcification (CAC) is an established imaging biomarker of subclinical atherosclerosis, but its relationship to diurnal preference is not well studied. We investigated the association between chronotype and CAC in the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort. Participants aged 50-64 years were randomly recruited and underwent extensive examination including imaging and accelerometry-assessed physical activity. 771 participants (47.3 % male, 57.6 ± 4.4 years) were included in this cross-sectional analysis. CAC was assessed by non-contrast computed tomography, and a CAC score > 10 was considered significant calcification. Self-assessed chronotype was classified as extreme morning, moderate morning, intermediate, moderate evening, or extreme evening. 10-year risk of first-onset cardiovascular disease was estimated by the Systemic Coronary Risk Evaluation 2 (SCORE2). Significant CAC was present in 29 % of the cohort. CAC prevalence increased from extreme morning to extreme evening type (22 %, 28 %, 29 %, 27 %, 41 % respectively, p = 0.018). In a multivariate logistic regression model controlling for confounders, extreme evening chronotype was independently associated with increased CAC prevalence compared to extreme morning type (OR 1.90, [95%CI 1.04-3.46], p = 0.037). When stratified by SCORE2 risk category (low: <5 %; moderate: 5 to <10 %; high: ≥10 %), significant CAC was most prevalent among extreme evening chronotypes in the low and moderate-risk groups, while chronotype seemed less important in the high-risk group (p = 0.011, p = 0.023, p = 0.86, respectively). Our findings suggest circadian factors may play an important role in atherosclerosis and should be considered in early cardiovascular prevention.

Eveningness is associated with sedentary behavior and increased 10-year risk of cardiovascular disease: the SCAPIS pilot cohort.

Chronotype reflects individual preferences for timing activities throughout the day, determined by the circadian system, environment and behavior. The relationship between chronotype, physical activity, and cardiovascular health has not been established. We studied the association between chronotype, physical activity patterns, and an estimated 10-year risk of first-onset cardiovascular disease (CVD) in the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort. A cross-sectional analysis was performed in a middle-aged population (n = 812, 48% male). Self-assessed chronotype was classified as extreme morning, moderate morning, intermediate, moderate evening, or extreme evening. Time spent sedentary (SED) and in moderate to vigorous physical activity (MVPA) were derived from hip accelerometer. The newly introduced Systematic COronary Risk Evaluation 2 (SCORE2) model was used to estimate CVD risk based on gender, age, smoking status, systolic blood pressure, and non-HDL cholesterol. Extreme evening chronotypes exhibited the most sedentary lifestyle and least MVPA (55.3 ± 10.2 and 5.3 ± 2.9% of wear-time, respectively), with a dose-dependent relationship between chronotype and SED/MVPA (p < 0.001 and p = 0.001, respectively). In a multivariate generalized linear regression model, extreme evening chronotype was associated with increased SCORE2 risk compared to extreme morning type independent of confounders (ß = 0.45, SE = 0.21, p = 0.031). Mediation analysis indicated SED was a significant mediator of the relationship between chronotype and SCORE2. Evening chronotype is associated with unhealthier physical activity patterns and poorer cardiovascular health compared to morning chronotype. Chronotype should be considered in lifestyle counseling and primary prevention programs as a potential modifiable risk factor.

Light therapy with boxes or glasses to counteract effects of acute sleep deprivation.

Sleep deprivation, in the context of shift work, is an increasing major public health issue. We aimed to determine whether early light administration can counteract sleep deprivation effects, and to compare LED-glasses with a traditional light therapy box. This cross-over design study included 18 individuals exposed to light therapy for 30 minutes at 5 am after one night of complete sleep deprivation, to mimic the night shift condition. Individuals were randomly exposed to 10,000 Lux light box, 2,000 Lux LED blue-enriched glasses, and control (ambient dim-light at 8 lux). Alertness, cognition and mood were assessed throughout the night and following morning. Five women and 13 men (mean 24.78 year old) presented with a progressive and increasing alteration of alertness, cognition, and mood during each sleep deprivation. A rebound was observed at 8 am resulting from the circadian drive overriding cumulative sleep homeostatic effects. Morning light significantly improved sleepiness and sustained attention from 5 to 7 am. These effects were comparable between devices and significantly different from control. Both devices were overall well and similarly tolerated. Early morning light therapy in the condition of sleep loss may have broad practical applications to improve sleepiness, sustained attention and subsequent risk of accidents.