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
Robust circadian rhythms are essential for optimal health. The central circadian clock controls temperature rhythms, which are known to organize the timing of peripheral circadian rhythms in rodents. In humans, however, it is unknown whether temperature rhythms relate to the organization of circadian rhythms throughout the body. We assessed core body temperature amplitude and the rhythmicity of 929 blood plasma metabolites across a 40-h constant routine protocol, controlling for behavioral and environmental factors that mask endogenous temperature rhythms, in 23 healthy individuals (mean [± SD] age = 25.4 ± 5.7 years, 5 women). Valid core body temperature data were available in 17/23 (mean [± SD] age = 25.6 ± 6.3 years, 1 woman). Individuals with higher core body temperature amplitude had a greater number of metabolites exhibiting circadian rhythms (R2 = 0.37, p = .009). Higher core body temperature amplitude was also associated with less variability in the free-fitted periods of metabolite rhythms within an individual (R2 = 0.47, p = .002). These findings indicate that a more robust central circadian clock is associated with greater organization of circadian metabolite rhythms in humans. Metabolite rhythms may therefore provide a window into the strength of the central circadian clock.
Subject(s)
Body Temperature , Circadian Rhythm , Humans , Female , Circadian Rhythm/physiology , Male , Adult , Young Adult , Circadian Clocks/physiology , Temperature , MetabolomeABSTRACT
In humans, the nocturnal secretion of melatonin by the pineal gland is suppressed by ocular exposure to light. In the laboratory, melatonin suppression is a biomarker for this neuroendocrine pathway. Recent work has found that individuals differ substantially in their melatonin-suppressive response to light, with the most sensitive individuals being up to 60 times more sensitive than the least sensitive individuals. Planning experiments with melatonin suppression as an outcome needs to incorporate these individual differences, particularly in common resource-limited scenarios where running within-subjects studies at multiple light levels is costly and resource-intensive and may not be feasible with respect to participant compliance. Here, we present a novel framework for virtual laboratory melatonin suppression experiments, incorporating a Bayesian statistical model. We provide a Shiny web app for power analyses that allows users to modify various experimental parameters (sample size, individual-level heterogeneity, statistical significance threshold, light levels), and simulate a systematic shift in sensitivity (e.g., due to a pharmacological or other intervention). Our framework helps experimenters to design compelling and robust studies, offering novel insights into the underlying biological variability in melatonin suppression relevant for practical applications.
ABSTRACT
OBJECTIVES: This study assessed whether there was a time-of-day effect on nausea reports in participants during studies employing circadian protocols. METHODS: Visual-analog-scales of nausea ratings were recorded from 34 participants (18-70years; 18 women) during forced desynchrony studies, where meals were scheduled at different circadian phases. Subjective nausea reports from a further 81 participants (18-35years; 36 women) were recorded during constant routine studies, where they ate identical isocaloric hourly snacks for 36-40 hours. RESULTS: Feelings of nausea varied by circadian phase in the forced desynchrony studies, peaking during the biological night. Nausea during the constant routine was reported by 27% of participants, commencing 2.9 ± 5.2 hours after the midpoint of usual sleep timing, but was never reported to start in the evening (4-9 PM). CONCLUSIONS: Nausea occurred more often during the biological night and early morning hours. This timing is relevant to overnight and early morning shift workers and suggests that a strategy to counteract that is to pay careful attention to meal timing.
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OBJECTIVES: Facial recognition is one of the key functions of the human brain, and linking a face to a name is critical in many social and occupational settings. This study assessed circadian- and wake-dependent effects on face-name recognition in healthy adults. METHODS: Thirteen healthy adults (20-70years; 7 F) were studied in a 39-day inpatient protocol that included 3weeks of 28 hours forced desynchrony with sleep restriction (6.5:21.5 hours sleep:wake). Starting 3 hours after scheduled wake, 6 novel face-name pairs were presented every 4 waking hours; recognition was tested 2 hours later. Performance data were averaged across â¼4 hours circadian phase or time-awake bins. RESULTS: Face-name recognition deteriorated with increased time awake (p < .0001) and exhibited significant circadian variation (p < .0001), with worst performance shortly after the core temperature nadir. There was a significant interaction between sex and circadian phase (p = .0177), with women performing significantly better than men at all circadian phases except 60° and 120°. Women exhibited a significantly higher amplitude than men during the third week of forced desynchrony (p < .01). CONCLUSIONS: Like many other aspects of neurobehavioral performance, recalling face-name associations is impacted by both duration of time awake and circadian phase. These results have implications for face recognition testing in medical contexts, such as in testing for dementia, because performance may be impacted by sleep deficiency and the time of testing.
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
OBJECTIVES: For optimal health and well-being the sleep episode and the circadian timing system should be properly aligned. We evaluated the effectiveness of different dynamic light and sleep/wake shift schedules for rapid circadian entrainment following an 8-hour advance of sleep. METHODS: Forty-three healthy participants completed an 8-day inpatient protocol in which the 8-hour sleep episode was advanced by 8 hours. Participants were assigned to one of five conditions: (1) dim ambient WHITE light and GRADUAL shift in which the sleep episode was incrementally advanced over 5days; (2) dim GREEN, short-wavelength (â¼504 nm) polychromatic light and GRADUAL shift; (3) dim WHITE light and SLAM shift, including an abrupt 8-hour advance on day 3 following an extended 32-hour wake episode; (4) GREEN light and SLAM shift; or (5) COMBINED (higher illuminance WHITE plus GREEN) light and modified SLAM shift with 2 short naps scheduled on the day prior to the abrupt advance. Phase shifts of the plasma dim light melatonin onset and sleep measures were compared to examine effects of protocol condition. RESULTS: After 5days, the COMBINED light/modified SLAM shift condition showed larger phase advances of dim light melatonin onset (4.02 ± 1.13 hours) compared to the other 4 conditions (range 1.50 ± 0.96-2.83 ± 2.23 hours; p < .05) and resulted in increased REM sleep duration and fewer sleep disruptions. CONCLUSIONS: Consideration of the type of shift and the illuminance and wavelength of light may assist in designing lighting countermeasures to sleep and circadian disruption, which has implications for jetlag, shiftwork, and circadian rhythm sleep disorders.
ABSTRACT
BACKGROUND: Excessive daytime sleepiness (EDS), experienced in 10% to 20% of the population, has been associated with cardiovascular disease and death. However, the condition is heterogeneous and is prevalent in individuals having short and long sleep duration. We sought to clarify the relationship between sleep duration subtypes of EDS with cardiovascular outcomes, accounting for these subtypes. METHODS AND RESULTS: We defined 3 sleep duration subtypes of excessive daytime sleepiness: normal (6-9 hours), short (<6 hours), and long (>9 hours), and compared these with a nonsleepy, normal-sleep-duration reference group. We analyzed their associations with incident myocardial infarction (MI) and stroke using medical records of 355 901 UK Biobank participants and performed 2-sample Mendelian randomization for each outcome. Compared with healthy sleep, long-sleep EDS was associated with an 83% increased rate of MI (hazard ratio, 1.83 [95% CI, 1.21-2.77]) during 8.2-year median follow-up, adjusting for multiple health and sociodemographic factors. Mendelian randomization analysis provided supporting evidence of a causal role for a genetic long-sleep EDS subtype in MI (inverse-variance weighted ß=1.995, P=0.001). In contrast, we did not find evidence that other subtypes of EDS were associated with incident MI or any associations with stroke (P>0.05). CONCLUSIONS: Our study suggests the previous evidence linking EDS with increased cardiovascular disease risk may be primarily driven by the effect of its long-sleep subtype on higher risk of MI. Underlying mechanisms remain to be investigated but may involve sleep irregularity and circadian disruption, suggesting a need for novel interventions in this population.
Subject(s)
Cardiovascular Diseases , Disorders of Excessive Somnolence , Myocardial Infarction , Stroke , Humans , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/genetics , Disorders of Excessive Somnolence/diagnosis , Disorders of Excessive Somnolence/epidemiology , Disorders of Excessive Somnolence/genetics , Sleep , Myocardial Infarction/epidemiology , Myocardial Infarction/genetics , Myocardial Infarction/complications , Stroke/diagnosis , Stroke/epidemiology , Stroke/geneticsABSTRACT
Light is the main environmental signal synchronizing circadian rhythms to the 24-hour light-dark cycle. Recent research has identified significant inter-individual variability in the sensitivity of the circadian system to light as measured by, among other indicators, melatonin suppression in response to light. These inter-individual differences in light sensitivity could result in differential vulnerability to circadian disruption and related impacts on health. A growing body of experimental evidence points to specific factors which are associated with variability in the melatonin suppression response; however, no review to date has summarized this research to present a comprehensive summary of current knowledge. The aim of this review is to provide an overview of the state of this evidence, which to date spans demographic, environmental, health-related, and genetic characteristics. Overall, we find that there is evidence of inter-individual differences for the majority of the characteristics examined, although research on many factors remains limited. Knowledge of individual factors that are linked to light sensitivity could inform improved lighting personalization, as well as the use of measures of light sensitivity to determine disease phenotypes and treatment recommendations.
Subject(s)
Circadian Rhythm , Melatonin , Humans , Circadian Rhythm/physiology , Photophobia , IndividualityABSTRACT
STUDY OBJECTIVES: Light is the main time cue for the human circadian system. Sleep and light are intrinsically linked; light exposure patterns can influence sleep patterns and sleep can influence light exposure patterns. However, metrics for quantifying light regularity are lacking, and the relationship between sleep and light regularity is underexplored. We developed new metrics for light regularity and demonstrated their utility in adolescents, across school term and vacation. METHODS: Daily sleep/wake and light patterns were measured using wrist actigraphy in 75 adolescents (54% male, 17.17 ± 0.83 years) over 2 weeks of school term and a subsequent 2-week vacation. The Sleep Regularity Index (SRI) and social jetlag were computed for each 2-week block. Light regularity was assessed using (1) variation in mean daily light timing (MLiT); (2) variation in daily photoperiod; and (3) the Light Regularity Index (LRI). Associations between SRI and each light regularity metric were examined, and within-individual changes in metrics were examined between school and vacation. RESULTS: Higher SRI was significantly associated with more regular LRI scores during both school and vacation. There were no significant associations of SRI with variation in MLiT or daily photoperiod. Compared to school term, all three light regularity metrics were less variable during the vacation. CONCLUSIONS: Light regularity is a multidimensional construct, which until now has not been formally defined. Irregular sleep patterns are associated with lower LRI, indicating that irregular sleepers also have irregular light inputs to the circadian system, which likely contributes to circadian disruption.
Subject(s)
Circadian Rhythm , Light , Photoperiod , Sleep , Lighting , Humans , Male , Female , Adolescent , Sleep Duration/radiation effects , Circadian Rhythm/physiology , Circadian Rhythm/radiation effects , Sleep/physiology , Sleep/radiation effects , Holidays , Leisure Activities , Jet Lag Syndrome , Time Factors , Schools , Cues , ActigraphyABSTRACT
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: Cancer patients often describe poor sleep quality and sleep disruption as contributors to poor quality of life (QoL). In a cross-sectional study of post-treatment breast, endometrial, and melanoma cancer patients, we used actigraphy to quantify sleep regularity using the sleep regularity index (SRI), and examined relationships with reported sleep symptoms and QoL. Methods: Participants were recruited post-primary treatment (35 diagnosed with breast cancer, 24 endometrial cancer, and 29 melanoma) and wore an actigraphy device for up to 2 weeks and SRI was calculated. Self-report questionnaires for cancer-related QoL [European Organization for Research and Treatment of Cancer EORTC (QLQ-C30)] were completed. Data were compared using analysis of variance (ANOVA) or Chi-Square tests. Multivariate linear regression analysis was used to determine independent variable predictors for questionnaire-derived data. Results: Age distribution was similar between cohorts. Endometrial and breast cancer cohorts were predominantly female, as expected, and body mass index (BMI) was higher in the endometrial cancer cohort, followed by breast and melanoma. There were no differences between tumor groups in: total sleep time, sleep onset latency, bedtime, and SRI (breast 80.9 ± 8.0, endometrial 80.3 ± 12.2, and melanoma 81.4 ± 7.0) (all p > 0.05). A higher SRI was associated with both better functional and symptom scores, including increased global QoL, better physical functioning, less sleepiness and fatigue, better sleep quality, and associated with less nausea/vomiting, dyspnea, and diarrhea (all p < 0.05). Conclusion: In cancer patients post-treatment, greater sleep regularity is associated with increased global QoL, as well as better physical functioning and fewer cancer related symptoms. Improving sleep regularity may improve QoL for cancer patients.
ABSTRACT
Light has many non-visual effects on human physiology, including alterations in sleep, mood, and alertness. These effects are mainly mediated by photoreceptors containing the photopigment melanopsin, which has a peak sensitivity to short wavelength ('blue') light. Commercially available light sensors are commonly wrist-worn and report photopic illuminance and are calibrated to perceive visual brightness and hence cannot be used to investigate the non-visual impacts of light. In this paper, we report the development of a wearable spectrophotometer designed to be worn as a pendant or affixed to clothing to capture spectral power density data close to eye level in the visible wavelength range 380-780 nm. From this, the relative impact of a given light stimulus can be determined for each photoreceptive input in the human eye by calculating effective illuminances. This device showed high accuracy for all effective illuminances while measuring a range of commonly encountered light sources by calibrating for directional response, dark noise, sensor saturation, non-linearity, stray-light and spectral response. Features of the device include IoT-integration, onboard data storage and processing, Bluetooth Low Energy (BLE) enabled data transfer, and cloud storage in one cohesive unit.
Subject(s)
Light , Photoreceptor Cells, Vertebrate/physiology , Spectrophotometry/instrumentation , Wearable Electronic Devices , Calibration , Equipment Design , Humans , LuminescenceABSTRACT
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
Light improves mood. The amygdala plays a critical role in regulating emotion, including fear-related responses. In rodents the amygdala receives direct light input from the retina, and light may play a role in fear-related learning. A direct effect of light on the amygdala represents a plausible mechanism of action for light's mood-elevating effects in humans. However, the effect of light on activity in the amygdala in humans is not well understood. We examined the effect of passive dim-to-moderate white light exposure on activation of the amygdala in healthy young adults using the BOLD fMRI response (3T Siemens scanner; n = 23). Participants were exposed to alternating 30s blocks of light (10 lux or 100 lux) and dark (<1 lux), with each light intensity being presented separately. Light, compared with dark, suppressed activity in the amygdala. Moderate light exposure resulted in greater suppression of amygdala activity than dim light. Furthermore, functional connectivity between the amygdala and ventro-medial prefrontal cortex was enhanced during light relative to dark. These effects may contribute to light's mood-elevating effects, via a reduction in negative, fear-related affect and enhanced processing of negative emotion.
Subject(s)
Amygdala/physiology , Emotions/physiology , Fear/physiology , Prefrontal Cortex/physiology , Adolescent , Adult , Brain Mapping/methods , Female , Humans , Image Processing, Computer-Assisted/methods , Light , Magnetic Resonance Imaging/methods , Male , Neural Pathways/physiology , Young AdultABSTRACT
Late diurnal preference has been linked to poorer mental health outcomes, but the understanding of the causal role of diurnal preference on mental health and wellbeing is currently limited. Late diurnal preference is often associated with circadian misalignment (a mismatch between the timing of the endogenous circadian system and behavioural rhythms), so that evening people live more frequently against their internal clock. This study aims to quantify the causal contribution of diurnal preference on mental health outcomes, including anxiety, depression and general wellbeing and test the hypothesis that more misaligned individuals have poorer mental health and wellbeing using an actigraphy-based measure of circadian misalignment. Multiple Mendelian Randomisation (MR) approaches were used to test causal pathways between diurnal preference and seven well-validated mental health and wellbeing outcomes in up to 451,025 individuals. In addition, observational analyses tested the association between a novel, objective measure of behavioural misalignment (Composite Phase Deviation, CPD) and seven mental health and wellbeing outcomes. Using genetic instruments identified in the largest GWAS for diurnal preference, we provide robust evidence that early diurnal preference is protective for depression and improves wellbeing. For example, using one-sample MR, a twofold higher genetic liability of morningness was associated with lower odds of depressive symptoms (OR: 0.92, 95% CI: 0.88, 0.97). It is possible that behavioural factors including circadian misalignment may contribute in the chronotype depression relationship, but further work is needed to confirm these findings.
Subject(s)
Circadian Rhythm , Mental Health , Anxiety/genetics , Circadian Rhythm/genetics , Humans , Risk Factors , Sleep/genetics , Surveys and QuestionnairesABSTRACT
Polycystic ovary syndrome (PCOS) is associated with a higher prevalence of sleep disturbances and obesity. Treatment of PCOS includes modifying lifestyle behaviours associated with weight management. However, poor sleep in the non-PCOS population has been associated with poorer lifestyle behaviours. The aim was to investigate whether sleep disturbance confounds or modifies the association between lifestyle factors and PCOS. This was a cross-sectional analysis from the Australian Longitudinal Study on Women's Health cohort aged 31-36 years in 2009 were analysed (n 6067, 464 PCOS, 5603 non-PCOS). Self-reported data were collected on PCOS, anthropometry, validated modified version of the Active Australia Physical Activity survey, validated FFQ and sleep disturbances through latent class analysis. Women with PCOS had greater adverse sleep symptoms including severe tiredness (P = 0·001), difficulty sleeping (P < 0·001) and restless sleep (P < 0·001), compared with women without PCOS. Women with PCOS also had higher energy consumption (6911 (sd 2453) v. 6654 (sd 2215) kJ, P = 0·017), fibre intake (19·8 (sd 7·8) v. 18·9 (sd 6·9) g, P = 0·012) and diet quality (dietary guidelines index (DGI)) (88·1 (sd 11·6) v. 86·7 (sd 11·1), P = 0·008), lower glycaemic index (50·2 (sd 4·0) v. 50·7 (sd 3·9), P = 0·021) and increased sedentary behaviour (6·3 (sd 2·8) v. 5·9 (sd 2·8) h, P = 0·009). There was a significant interaction between PCOS and sleep disturbances for DGI (P = 0·035), therefore only for women who had adequate sleep was PCOS associated with a higher DGI. For women with poorer sleep, there was no association between PCOS and DGI. The association between PCOS and improved diet quality may only be maintained if women can obtain enough good quality sleep.