ABSTRACT
Women typically sleep and wake earlier than men and have been shown to have earlier circadian timing relative to the light/dark cycle that synchronizes the clock. A potential mechanism for earlier timing in women is an altered response of the circadian system to evening light. We characterized individual-level dose-response curves for light-induced melatonin suppression using a within-subjects protocol. Fifty-six participants (29 women, 27 men; aged 18-30 years) were exposed to a range of light illuminances (10, 30, 50, 100, 200, 400, and 2000 lux) using melatonin suppression relative to a dim control (<1 lux) as a marker of light sensitivity. Women were free from hormonal contraception. To examine the potential influence of sex hormones, estradiol and progesterone was examined in women and testosterone was examined in a subset of men. Menstrual phase was monitored using self-reports and estradiol and progesterone levels. Women exhibited significantly greater melatonin suppression than men under the 400-lux and 2000-lux conditions, but not under lower light conditions (10-200 lux). Light sensitivity did not differ by menstrual phase, nor was it associated with levels of estradiol, progesterone, or testosterone, suggesting the sex differences in light sensitivity were not acutely driven by circulating levels of sex hormones. These results suggest that sex differences in circadian timing are not due to differences in the response to dim/moderate light exposures typically experienced in the evening. The finding of increased bright light sensitivity in women suggests that sex differences in circadian timing could plausibly instead be driven by a greater sensitivity to phase-advancing effects of bright morning light.
Subject(s)
Circadian Rhythm , Light , Melatonin , Humans , Female , Adult , Circadian Rhythm/physiology , Adolescent , Young Adult , Male , Melatonin/metabolism , Estradiol/blood , Progesterone/blood , Progesterone/metabolism , Testosterone/blood , Menstrual Cycle/physiologyABSTRACT
Background: Light at night disrupts circadian rhythms, and circadian disruption is a risk factor for type 2 diabetes. Whether personal light exposure predicts diabetes risk has not been demonstrated in a large prospective cohort. We therefore assessed whether personal light exposure patterns predicted risk of incident type 2 diabetes in UK Biobank participants, using â¼13 million hours of light sensor data. Methods: Participants (N = 84,790, age (M ± SD) = 62.3 ± 7.9 years, 58% female) wore light sensors for one week, recording day and night light exposure. Circadian amplitude and phase were modeled from weekly light data. Incident type 2 diabetes was recorded (1997 cases; 7.9 ± 1.2 years follow-up; excluding diabetes cases prior to light-tracking). Risk of incident type 2 diabetes was assessed as a function of day and night light, circadian phase, and circadian amplitude, adjusting for age, sex, ethnicity, socioeconomic and lifestyle factors, and polygenic risk. Findings: Compared to people with dark nights (0-50th percentiles), diabetes risk was incrementally higher across brighter night light exposure percentiles (50-70th: multivariable-adjusted HR = 1.29 [1.14-1.46]; 70-90th: 1.39 [1.24-1.57]; and 90-100th: 1.53 [1.32-1.77]). Diabetes risk was higher in people with lower modeled circadian amplitude (aHR = 1.07 [1.03-1.10] per SD), and with early or late circadian phase (aHR range: 1.06-1.26). Night light and polygenic risk independently predicted higher diabetes risk. The difference in diabetes risk between people with bright and dark nights was similar to the difference between people with low and moderate genetic risk. Interpretation: Type 2 diabetes risk was higher in people exposed to brighter night light, and in people exposed to light patterns that may disrupt circadian rhythms. Avoidance of light at night could be a simple and cost-effective recommendation that mitigates risk of diabetes, even in those with high genetic risk. Funding: Australian Government Research Training Program.
ABSTRACT
Abnormally short and long sleep are associated with premature mortality, and achieving optimal sleep duration has been the focus of sleep health guidelines. Emerging research demonstrates that sleep regularity, the day-to-day consistency of sleep-wake timing, can be a stronger predictor for some health outcomes than sleep duration. The role of sleep regularity in mortality, however, has not been investigated in a large cohort with objective data. We therefore aimed to compare how sleep regularity and duration predicted risk for all-cause and cause-specific mortality. We calculated Sleep Regularity Index (SRI) scores fromâ >â 10 million hours of accelerometer data in 60 977 UK Biobank participants (62.8â ±â 7.8 years, 55.0% female, median[IQR] SRI: 81.0[73.8-86.3]). Mortality was reported up to 7.8 years after accelerometer recording in 1859 participants (4.84 deaths per 1000 person-years, mean (±SD) follow-up of 6.30â ±â 0.83 years). Higher sleep regularity was associated with a 20%-48% lower risk of all-cause mortality (pâ <â .001 to pâ =â 0.004), a 16%-39% lower risk of cancer mortality (pâ <â 0.001 to pâ =â 0.017), and a 22%-57% lower risk of cardiometabolic mortality (pâ <â 0.001 to pâ =â 0.048), across the top four SRI quintiles compared to the least regular quintile. Results were adjusted for age, sex, ethnicity, and sociodemographic, lifestyle, and health factors. Sleep regularity was a stronger predictor of all-cause mortality than sleep duration, by comparing equivalent mortality models, and by comparing nested SRI-mortality models with and without sleep duration (pâ =â 0.14-0.20). These findings indicate that sleep regularity is an important predictor of mortality risk and is a stronger predictor than sleep duration. Sleep regularity may be a simple, effective target for improving general health and survival.
Subject(s)
Life Style , Sleep , Humans , Female , Male , Prospective Studies , Actigraphy , Time FactorsABSTRACT
STUDY OBJECTIVES: Light is the primary stimulus for synchronizing the circadian clock in humans. There are very large interindividual differences in the sensitivity of the circadian clock to light. Little is currently known about the genetic basis for these interindividual differences. METHODS: We performed a genome-wide gene-by-environment interaction study (GWIS) in 280 897 individuals from the UK Biobank cohort to identify genetic variants that moderate the effect of daytime light exposure on chronotype (individual time of day preference), acting as "light sensitivity" variants for the impact of daylight on the circadian system. RESULTS: We identified a genome-wide significant SNP mapped to the ARL14EP gene (rs3847634; p < 5 × 10-8), where additional minor alleles were found to enhance the morningness effect of daytime light exposure (ßGxE = -.03, SE = 0.005) and were associated with increased gene ARL14EP expression in brain and retinal tissues. Gene-property analysis showed light sensitivity loci were enriched for genes in the G protein-coupled glutamate receptor signaling pathway and genes expressed in Per2+ hypothalamic neurons. Linkage disequilibrium score regression identified Bonferroni significant genetic correlations of greater light sensitivity GWIS with later chronotype and shorter sleep duration. Greater light sensitivity was nominally genetically correlated with insomnia symptoms and risk for post-traumatic stress disorder (PTSD). CONCLUSIONS: This study is the first to assess light as an important exposure in the genomics of chronotype and is a critical first step in uncovering the genetic architecture of human circadian light sensitivity and its links to sleep and mental health.
Subject(s)
Circadian Clocks , Sleep Initiation and Maintenance Disorders , Sleep Wake Disorders , Humans , Chronotype , Circadian Clocks/physiology , Circadian Rhythm/genetics , Sleep/genetics , GenomeABSTRACT
BACKGROUND: Light has powerful effects on mood, sleep, and the circadian system. Humans evolved in an environment with a clear distinction between day and night, but our modern environments have blurred this distinction. Negative effects of light exposure at night have been well characterized. The importance of daytime light exposure has been less well characterized. Here we examine the cross-sectional and longitudinal associations of time spent in daytime outdoor light with mood, sleep, and circadian-related outcomes. METHODS: Participants were drawn from the UK Biobank cohort, a large study of UK adults (n = 502,000; 37-73 years old; 54% women). RESULTS: UK Biobank participants reported spending a median of 2.5 daylight hours (IQR = 1.5-3.5 h) outdoors per day. Each additional hour spent outdoors during the day was associated with lower odds of lifetime major depressive disorder (95% CI OR:0.92-0.98), antidepressant usage (OR:0.92-0.98), less frequent anhedonia (OR:0.93-0.96) and low mood (OR:0.87-0.90), greater happiness (OR:1.41-1.48) and lower neuroticism (incident rate ratio, IRR:0.95-0.96), independent of demographic, lifestyle, and employment covariates. In addition, each hour of daytime light was associated with greater ease of getting up (OR:1.46-1.49), less frequent tiredness (OR:0.80-0.82), fewer insomnia symptoms (OR:0.94-0.97), and earlier chronotype (adjusted odds ratio; OR:0.75-0.77). Auto-Regressive Cross-Lagged (ARCL) models were used to examine the longitudinal association of time spent in outdoor light at baseline with later mood-, sleep- and circadian-related outcomes reported at time point 2. Overall, longitudinal associations support cross-sectional findings, though generally with smaller effect sizes. LIMITATIONS: Future studies that examine the intensity of daytime light exposure at the ocular level are needed. CONCLUSIONS: Our findings suggest that low daytime light exposure is an important environmental risk factor for mood, sleep, and circadian-related outcomes.
Subject(s)
Circadian Rhythm , Depressive Disorder, Major , Adult , Aged , Biological Specimen Banks , Cross-Sectional Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Sleep , United Kingdom/epidemiologyABSTRACT
Mood states in bipolar disorder appear to be closely linked to changes in sleep and circadian function. It has been suggested that hypersensitivity of the circadian system to light may be a trait vulnerability for bipolar disorder. Healthy persons with emotional-behavioural traits associated with bipolar disorder also appear to exhibit problems with circadian rhythms, which may be associated with individual differences in light sensitivity. This study investigated the melanopsin-driven post-illumination pupil response (PIPR) in relation to emotional-behavioural traits associated with bipolar disorder (measured with the General Behavior Inventory) in a non-clinical group (nâ¯=â¯61). An increased PIPR was associated with increased bipolar disorder-related traits. Specifically, the hypomania scale of the General Behavior Inventory was associated with an increased post-blue PIPR. Further, both the full hypomania and shortened '7 Up' scales were significantly predicted by PIPR, after age, sex and depressive traits were controlled. These findings suggest that increased sensitivity to light may be a risk factor for mood problems in the general population, and support the idea that hypersensitivity to light is a trait vulnerability for, rather than symptom of, bipolar disorder.
Subject(s)
Bipolar Disorder/physiopathology , Bipolar Disorder/psychology , Photic Stimulation/methods , Photophobia/physiopathology , Photophobia/psychology , Reflex, Pupillary/physiology , Adolescent , Adult , Bipolar Disorder/diagnosis , Circadian Rhythm/physiology , Female , Humans , Individuality , Male , Photophobia/diagnosis , Sleep/physiology , Young AdultABSTRACT
Before the invention of electric lighting, humans were primarily exposed to intense (>300 lux) or dim (<30 lux) environmental light-stimuli at extreme ends of the circadian system's dose-response curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30-300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting. We characterized individual-level dose-response curves to light-induced melatonin suppression using a within-subjects protocol. Fifty-five participants (aged 18-30) were exposed to a dim control (<1 lux) and a range of experimental light levels (10-2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED50) was computed at individual and group levels. The group-level fitted ED50 was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED50 values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock's role in human health and disease.
Subject(s)
Circadian Clocks/physiology , Circadian Rhythm/physiology , Adult , Female , Humans , Individuality , Light , Lighting/methods , Male , Melatonin/metabolism , Young AdultABSTRACT
This study investigated the utility of the pupillary light reflex as a method of differentiating DSPD patients with delayed melatonin timing relative to desired/required sleep time (circadian type) and those with non-delayed melatonin timing (non-circadian type). All participants were young adults, with a total of 14 circadian DSPD patients (M = 28.14, SD = 5.26), 12 non-circadian DSPD patients (M = 29.42, SD = 11.51) and 51 healthy controls (M = 21.47 SD = 3.16) completing the protocol. All participants were free of central nervous system acting medications and abstained from caffeine and alcohol on the day of the assessment. Two pupillary light reflex measurements were completed by each participant, one with a 1s dim (~10 lux) light exposure, and one with a 1s bright (~1500 lux) light exposure. Circadian DSPD patients showed a significantly faster pupillary light reflex than both non-circadian DSPD patients and healthy controls. Non-circadian patients and healthy controls did not differ significantly. Receiver operating characteristic curves were generated to determine the utility of mean and maximum constriction velocity in differentiating the two DSPD phenotypes, and these demonstrated high levels of sensitivity (69.23--100%) and specificity (66.67-91.67%) at their optimal cut offs. The strongest predictor of DSPD phenotype was the mean constriction velocity to bright light (AUC = 0.87). These results support the potential for the pupillary light reflex to clinically differentiate between DSPD patients with normal vs. delayed circadian timing relative to desired bedtime, without the need for costly and time-consuming circadian assessments.
Subject(s)
Reflex, Pupillary/physiology , Sleep Disorders, Circadian Rhythm/diagnosis , Sleep Disorders, Circadian Rhythm/physiopathology , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/physiopathology , Adolescent , Adult , Case-Control Studies , Circadian Rhythm/physiology , Diagnosis, Differential , Diagnostic Errors , Female , Humans , Male , Phenotype , ROC Curve , Sleep Disorders, Circadian Rhythm/therapy , Sleep Wake Disorders/therapy , Young AdultABSTRACT
Study Objectives: To investigate sex differences in the effect of sleep deprivation on performance, accounting for menstrual phase in women. Methods: We examined alertness data from 124 healthy women and men (40 women, 84 men; aged 18-30 years) who maintained wakefulness for at least 30 hr in a laboratory setting using a constant routine protocol. Objective alertness was assessed every 2 hr using a 10 min psychomotor vigilance task. Subjective alertness was assessed every hour via the Karolinska Sleepiness Scale. Results: Women in the follicular phase of the menstrual cycle demonstrated the poorest level of performance. This poor performance was most pronounced at times corresponding to the typical sleep episode, demonstrating a window of vulnerability at night during this menstrual phase. At 24 hr awake, over 60 per cent of their responses were lapses of >500 ms and over one-third of their responses were longer lapses of at least 3 s in duration. Women in the luteal phase, however, were relatively protected from alertness failure, performing similar or better than both follicular-phase women and men. Conclusions: These results have important implications for education and intervention programs for shift workers, specifically during times of vulnerability to attentional failure that increase risk of injury.
Subject(s)
Attention/physiology , Follicular Phase/physiology , Luteal Phase/physiology , Psychomotor Performance/physiology , Sleep Deprivation/physiopathology , Adolescent , Adult , Female , Humans , Male , Sleep/physiology , Wakefulness/physiology , Young AdultABSTRACT
CONTEXT: Late adolescence is marked by a delay in sleep timing, which is partly driven by a delay shift of the circadian timing system. This study examined whether the sensitivity of the circadian system to light-the primary entraining stimulus to the circadian system-differs between pre- to mid-pubertal and late to postpubertal adolescents. OBJECTIVE: The study was designed to determine the influence of puberty on the sensitivity of the circadian system to light in humans. METHODS: Melatonin suppression to low and moderate light levels was assessed in 38 pre- to mid-pubertal (9.1-14.7 years) and 29 late to postpubertal (11.5-15.9 years) adolescents. They received 1 hour of four light levels on consecutive nights: approximately 0.1 (near-dark baseline condition), 15, 150, and 500 lux. One group received evening light beginning at 11:00 pm (n = 39); a second group received morning light beginning at 3:00 am (n = 28). Salivary melatonin was sampled every 30 minutes. Melatonin suppression for 15, 150, and 500 lux was calculated relative to unsuppressed baseline levels in the 0.1 lux setting, within individuals. RESULTS: The pre- to mid-pubertal group showed significantly greater melatonin suppression to 15 lux (9.2 ± 20.5%), 150 lux (26.0 ± 17.7%), and 500 lux (36.9 ± 11.4%) during evening light exposure compared to the late to postpubertal group (-5.3 ± 17.7%, 12.5 ± 17.3%, and 23.9 ± 21.7%, respectively; P < .05). No significant differences were seen between developmental groups in morning melatonin suppression. CONCLUSION: These results indicate support for a greater sensitivity to evening light in early pubertal children. The increased sensitivity to light in younger adolescents suggests that exposure to evening light could be particularly disruptive to sleep regulation for this group.