Melatonin Phase Research Articles

Circadian rhythms of melatonin and its relationship with anhedonia in patients with mood disorders: a cross-sectional study

BackgroundMood disorders are strongly associated with melatonin disturbances. However, it is unclear whether there is a difference in melatonin concentrations and melatonin circadian rhythm profiles between depression and bipolar disorder. In addition, the relationship between anhedonia, a common symptom of affective disorders, and its melatonin circadian rhythm remains under-investigated.MethodsThirty-four patients with depression disorder, 20 patients diagnosed with bipolar disorder and 21 healthy controls participated in this study. The Revised Physical Anhedonia Scale (RPAS) was performed to assess anhedonia. Saliva samples were collected from all subjects at fixed time points (a total of 14 points) in two consecutive days for measuring the melatonin concentrations to fit circadian rhythms of subjects. Melatonin circadian rhythms were compared between the three groups using ANOVA. Partial correlation analysis and linear regression analysis were used to explore the correlation between melatonin rhythm variables and anhedonia.ResultsWe found that the peak phase of melatonin in the depression group was significantly advanced compared to the control group (P < 0.001) and the bipolar disorder group (P = 0.004). The peak phase of melatonin and RPAS showed a negative correlation (P = 0.003) in depression patients, which was also demonstrated in the multiple linear regression model (B=-2.47, P = 0.006).ConclusionsThese results suggest that circadian rhythms of melatonin are differentiated in depression and bipolar disorder and correlate with anhedonia in depression. Future research needs to explore the neurobiological mechanisms linking anhedonia and melatonin circadian rhythms in depressed patients.

Effects of calibrated blue–yellow changes in light on the human circadian clock

Evening exposure to short-wavelength light can affect the circadian clock, sleep and alertness. Intrinsically photosensitive retinal ganglion cells expressing melanopsin are thought to be the primary drivers of these effects. Whether colour-sensitive cones also contribute is unclear. Here, using calibrated silent-substitution changes in light colour along the blue–yellow axis, we investigated whether mechanisms of colour vision affect the human circadian system and sleep. In a 32.5-h repeated within-subjects protocol, 16 healthy participants were exposed to three different light scenarios for 1 h starting 30 min after habitual bedtime: baseline control condition (93.5 photopic lux), intermittently flickering (1 Hz, 30 s on–off) yellow-bright light (123.5 photopic lux) and intermittently flickering blue-dim light (67.0 photopic lux), all calibrated to have equal melanopsin excitation. We did not find conclusive evidence for differences between the three lighting conditions regarding circadian melatonin phase delays, melatonin suppression, subjective sleepiness, psychomotor vigilance or sleep.The Stage 1 protocol for this Registered Report was accepted in principle on 9 September 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.13050215.v1.

The Timing of the Melatonin Onset and Phase Angle to Sleep Onset in Older Adults after Uncontrolled vs. Controlled Lighting Conditions.

The main aim of this study was to explore how melatonin onset timing and phase angle to bedtime in healthy older adults are impacted by prior light exposure. A total of 13 healthy older (ages 56-74) individuals were studied on two successive evenings. Prior to the first evening, the participants were in self-selected lighting conditions for the first 4-6 h of the day and then were in dim light (3 lux) until their scheduled bedtime. On the second day, individuals from Project A remained in the dim lighting conditions throughout the entire day but those in Project B were in more typical indoor lighting (~90 lux) throughout the day. On both evenings, hourly blood samples were collected and assayed for melatonin, and melatonin onset timing and phase angle to sleep onset was determined. Overall, melatonin onset was earlier and the phase angle was larger on Night 1 than on Night 2. In Project A there was no significant difference between melatonin onset on night 1 vs. night 2. However, in Project B melatonin onset was significantly later on Night 2 (in typical indoor lighting) than on Night 1 (in dim lighting). Our results suggest that in older people, uncontrolled bright light early in the day did not impact the timing of dim light melatonin onset (DLMO) when assessed later that same evening. However, in older adults, exposure to ordinary room light during melatonin phase assessment appeared to suppress melatonin, leading to a later observed time of melatonin onset, as has been reported previously for young adults.

Melanopic irradiance defines the impact of evening display light on sleep latency, melatonin and alertness

Evening light-emitting visual displays may disrupt sleep, suppress melatonin and increase alertness. Here, we control melanopic irradiance independent of display luminance and colour, in 72 healthy males 4 h before habitual bedtime and expose each of them to one of four luminance levels (i.e., dim light, smartphone, tablet or computer screen illuminance) at a low and a high melanopic irradiance setting. Low melanopic light shortens the time to fall asleep, attenuates evening melatonin suppression, reduces morning melatonin, advances evening melatonin onset and decreases alertness compared to high melanopic light. In addition, we observe dose-dependent increases in sleep latency, reductions in melatonin concentration and delays in melatonin onset as a function of melanopic irradiance—not so for subjective alertness. We identify melanopic irradiance as an appropriate parameter to mitigate the unwanted effects of screen use at night. Our results may help the many people who sit in front of screens in the evening or at night to fall asleep faster, feel sleepier, and have a more stable melatonin phase by spectrally tuning the visual display light without compromising the visual appearance.

SUNBATHING FOR IMPROVING THE SLEEP QUALITY OF THE ELDERLY

Background: Sleep changes is associated with the aging process. The elderly reported that they often had difficulty in falling and staying asleep Objective: This study purposed to determine the effect of sunbathing on improving the elderly’s sleep quality in Werda Nursing Home. Methods: A quasi-experimental was conducted with one group pre-post-test design. The population was 42 elderly in Werda Nursing Home. The sample was 38 respondents taken by quota sampling technique. The modified PSQI was used to collect data. Statistical analysis was using Mann Whitney showed a p-value of 0,000 smaller than α 0.05. Result: The study results showed that frequency of pre-test data before treatment obtained a mean of 7.06, in the post-test after being given treatment for 2 weeks, the mean obtained was 4.04. Conclusion: Sunbathing affected the elderly’s sleep quality. The sunlight had a double impact in enhancing melatonin through the retinohypothalamic duct and SCN and stimulating the nocturnal melatonin phase by rearranging the pacemaker.

Phenotypic divergence in sleep and circadian cycles linked by affective state and environmental risk related to psychosis.

Environmental cues influence circadian rhythm timing and neurochemicals involved in the regulation of affective behavior. How this interplay makes them a probable nonspecific risk factor for psychosis is unclear. We aimed to identify the relationship between environmental risk for psychosis and circadian timing phenotypes sampled from the general population. Using an online survey, we devised a cumulative risk exposure score for each of the 1898 survey respondents based on 23 empirically verified transdiagnostic risks for psychosis, three dimensions of affect severity, psychotic-like experiences, and help-seeking behavior. Quantitative phenotyping of sleep and circadian rhythms was undertaken using at-home polysomnography, melatonin and cortisol profiles, and 3-week rest-activity behavior in individuals with a high-risk exposure load (top 15% of survey respondents, n = 22) and low-risk exposure load (bottom 15% of respondents, n = 22). Psychiatric symptoms were present in 100% of the high-load participants and 14% of the low-load participants. Compared to those with a low-load, high-load participants showed a later melatonin phase which was reflected by a greater degree of dispersion in circadian timing. Phase relationships between later circadian melatonin phase and later actigraphic sleep onsets were maintained and these were strongly correlated with self-reported sleep mid-points. No differences were identified from polysomnography during sleep between groups. Distinguishing circadian timing from other sleep phenotypes will allow adaptation for dosage of time-directed intervention, useful in stabilizing circadian timekeeping physiology and potentially reducing the multisystemic disruption in mental health disorders.

Homeostatic response to sleep deprivation and circadian rhythmicity are intact in older adults with insomnia.

We examined whether homeostatic sleep drive and circadian rhythmicity differ in older adults with insomnia (OAI) compared to older good sleepers (GS). OAI (n = 37) and GS (n = 30) participated in a 60-h in-lab study with sleep deprivation and constant routine paradigms. Homeostatic sleep drive was assessed by examining the effect of sleep deprivation on delta EEG power and theta EEG power, and repeated sleep latency tests. Circadian rhythm was assessed with salivary melatonin (phase and amplitude), core body temperature (phase, amplitude, and mesor), and sleep latency during a constant routine paradigm. Mixed models were used to assess interactions of group (OAS vs GS) with homeostatic sleep and circadian effects. Compared to GS, OAI showed a greater linear increase in waking theta power during sleep deprivation, but the two groups did not show differential responses to sleep deprivation in delta EEG, or in repeated sleep latency tests. The two groups did not differ in circadian phase or amplitude of melatonin or core body temperature rhythms. OAI had a significantly elevated core body temperature mesor compared to GS. Homeostatic response to sleep deprivation was intact in OAI compared to GS; theta EEG power suggested a greater homeostatic response in OAI. Circadian rhythm amplitude and phase were similar in OAI compared to GS. Elevated body temperature mesor in OAI may indicate elevated physiological arousal. These findings suggest that effective treatments for insomnia in older adults may leverage intact sleep and circadian regulatory mechanisms, rather than repair defective sleep and circadian regulation.

Optimized office lighting advances melatonin phase and peripheral heat loss prior bedtime

Improving indoor lighting conditions at the workplace has the potential to support proper circadian entrainment of hormonal rhythms, sleep, and well-being. We tested the effects of optimized dynamic daylight and electric lighting on circadian phase of melatonin, cortisol and skin temperatures in office workers. We equipped one office room with an automated controller for blinds and electric lighting, optimized for dynamic lighting (= Test room), and a second room without any automated control (= Reference room). Young healthy participants (n = 34) spent five consecutive workdays in each room, where individual light exposure data, skin temperatures and saliva samples for melatonin and cortisol assessments were collected. Vertical illuminance in the Test room was 1177 ± 562 photopic lux (mean ± SD) , which was 320 lux higher than in the Reference room (p < 0.01). Melanopic equivalent daylight (D65) illuminance was 931 ± 484 melanopic lux in the Test room and 730 ± 390 melanopic lux in the Reference room (p < 0.01). Individual light exposures resulted in a 50 min earlier time of half-maximum accumulated illuminance in the Test than the Reference room (p < 0.05). The melatonin secretion onset and peripheral heat loss in the evening occurred significantly earlier with respect to habitual sleeptime in the Test compared to the Reference room (p < 0.05). Our findings suggest that optimized dynamic workplace lighting has the potential to promote earlier melatonin onset and peripheral heat loss prior bedtime, which may be beneficial for persons with a delayed circadian timing system.

Effects of Circadian Phase Tailored Light Therapy on Sleep, Mood, and Cognition in Alzheimer’s Disease: Preliminary Findings in a Pivotal Study

It is shown that the circadian system is affected in patients with Alzheimer’s disease (AD) even at an early stage of the disease and that such dysfunction may be detrimental to sleep, mood, and cognitive functioning. Light is a strong central modulator of the circadian rhythms and is potentially beneficial to mood and cognitive functioning via a direct effect or indirectly via its modulating effects on circadian rhythms. This study focuses on tracking the effect of light therapy on sleep quality, mood, and cognition in AD of mild/moderate severity. We performed a single-blind randomized controlled trial to investigate the effects of a light therapy treatment tailored to the individual circadian phase as measured by dim light melatonin onset (DLMO). Such a treatment induced an objective circadian phase shift consistent with the melatonin phase response curve to light exposure, led to a shortening of the phase angle DLMO-falling asleep time, and was associated with an improvement in subjective sleep quality and cognitive performance.

Sleep and circadian phenotype in people without cone-mediated vision: a case series of five CNGB3 and two CNGA3 patients.

Light exposure entrains the circadian clock through the intrinsically photosensitive retinal ganglion cells, which sense light in addition to the cone and rod photoreceptors. In congenital achromatopsia (prevalence 1:30–50 000), the cone system is non-functional, resulting in severe light avoidance and photophobia at daytime light levels. How this condition affects circadian and neuroendocrine responses to light is not known. In this case series of genetically confirmed congenital achromatopsia patients (n = 7; age 30–72 years; 6 women, 1 male), we examined survey-assessed sleep/circadian phenotype, self-reported visual function, sensitivity to light and use of spectral filters that modify chronic light exposure. In all but one patient, we measured rest-activity cycles using actigraphy over 3 weeks and measured the melatonin phase angle of entrainment using the dim-light melatonin onset. Owing to their light sensitivity, congenital achromatopsia patients used filters to reduce retinal illumination. Thus, congenital achromatopsia patients experienced severely attenuated light exposure. In aggregate, we found a tendency to a late chronotype. We found regular rest-activity patterns in all patients and normal phase angles of entrainment in participants with a measurable dim-light melatonin onset. Our results reveal that a functional cone system and exposure to daytime light intensities are not necessary for regular behavioural and hormonal entrainment, even when survey-assessed sleep and circadian phenotype indicated a tendency for a late chronotype and sleep problems in our congenital achromatopsia cohort.

Associations Between Chrononutrition With Sleep Quality and Melatonin Rhythm of Pregnant Women

Abstract Objectives Chrononutrition is referred to as a zeitgeber for its ability to synchronize the circadian rhythm. In addition to the role as circadian marker, sleep and melatonin are important factors for optimal maternal and infant outcomes. Understanding the chrononutrition factors associated with sleep quality and melatonin rhythm during pregnancy has practical importance for preventive care. Hence, this study aimed to examine the association between chrononutrition with sleep quality and melatonin rhythm during pregnancy. Methods A total of 114 primigravidas were recruited at randomly selected government maternal and child clinics in Kuala Lumpur, Malaysia. Gestational age and pre-pregnancy body mass index (BMI) were extracted from clinic records. Components of chrononutrition including meal timing, meal frequency, eating window, breakfast skipping, and night eating were assessed using 3-day food record. Sleep quality in the third trimester was determined using Pittsburgh Sleep Quality Index (PSQI). Subsample (n = 48) provided salivary samples at 4 time-points (9:00, 15:00, 21:00 and 3:00 h) over 24 hours for melatonin assay. Results The mean gestational age of participants was 33.0 (2.1) weeks; 13% were underweight and 22% were overweight/obese before pregnancy. Average daily meal frequency was 4.1 (0.9). The majority (68%) practiced a shorter eating window (≤12 hours); 25% skipped breakfast and 19% ate within 2 hours pre-bedtime. The prevalence of poor sleep among the participants was 56%. Mean salivary melatonin level was 19.6 (16.3) pmol/L. In the adjusted linear regression model, lower meal frequency and fat intake during dinner were significant predictors of poor sleep quality (β = −0.266, P = 0.035 and β = −0.232, P = 0.026, respectively). Eating nearer to bedtime was significantly associated with greater deviation of melatonin acrophase from mid-sleep clock time (β = −0.339, P = 0.043). Conclusions Findings suggested that unfavorable characteristics of chrononutrition may contribute to poor sleep and misalignment of melatonin phase. Components of chrononutrition may be incorporated into meal intervention to improve maternal sleep quality and circadian health. Funding Sources Research relating to this abstract was funded by the Ministry of Education Malaysia Fundamental Research Grant.

Effects of Organic Light-Emitting Diodes on Circadian Rhythm and Sleep.

ObjectiveOrganic light-emitting diodes (OLEDs) emit less blue light than traditional light-emitting diodes (LEDs), and we previously found that early-night OLED light exposure (LE) delays the melatonin phase by less than LED at a color temperature of 4,000 K. As a follow-up study, we investigated the effects of OLED and LED at a different color temperature (3,000 K) on melatonin profile, sleep, and vigilance. Methods24 healthy subjects (27.5±5.1 years) were exposed to three light conditions [OLED, LED, and dim light (DL)] from 17:30 to 24:00, in a random order and with a 1-week interval. Saliva samples for melatonin were taken every hour from 18:00 to 24:00. Polysomnography (PSG) and a psychomotor vigilance test (PVT) were performed. ResultsMelatonin onset time was significantly delayed under OLED and LED compared with DL, with no significant difference between OLED and LED. The mean melatonin level at 24:00 under LED was lower than that under DL, but there was no significant difference between OLED LE and DL. The percentage of slow wave sleep (N3) in LED was significantly lower than in OLED. ConclusionExposure to light in the evening can suppress melatonin secretion late at night and disturb deep sleep, and those effects are slightly worse under LED than OLED.

Prolonged, Controlled Daytime versus Delayed Eating Impacts Weight and Metabolism

A delayed eating schedule is associated with increased risk of obesity and metabolic dysfunction in humans.1-9 However, there are no prolonged, highly controlled experimental studies testing the effects of meal timing on weight and metabolism in adults with a body mass index (BMI) of 19-27kg/m2.10-18 Twelve healthy adults (age: 26.3± 3.4 years; BMI: 21.9± 1.7kg/m2; 5 females) participated in a randomized crossover study in free-living conditions. Three meals and two snacks with comparable energy and macronutrient contents were provided during two, 8-week, counterbalanced conditions separated by a 2-week washout period: (1) daytime (intake limited to 0800 h-1900 h) and (2) delayed (intake limited to 1200 h-2300 h). Sleep-wake cycles and exercise levels were held constant. Weight, adiposity, energy expenditure, and circadian profiles of hormones and metabolites were assessed during four inpatient visits occurring before and after each condition. Body weight, insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR]), trunk-to-leg fat ratio, resting energy expenditure, respiratory quotient, and fasting glucose, insulin, total and high-density lipoprotein (dHDL) cholesterol, and adiponectin decreased on the daytime compared to the delayed schedule. These measures, as well as triglycerides, increased on the delayed compared to the daytime schedule (effect size range: d= 0.397-1.019). Circadian phase and amplitude of melatonin, cortisol, ghrelin, leptin, and glucose were not differentially altered by the eating schedules. Overall, an 8-week daytime eating schedule, compared to a delayed eating schedule, promotes weight loss and improvements in energy metabolism and insulin in adults with BMI 19-27kg/m2, underscoring the efficacy and feasibility of daytime eating as a behavioral modification for real-world conditions.

0047 The Change in Melatonin Rhythm Depending on Dementia Severity in Alzheimer’s Disease (AD) Patients

Abstract Introduction In Alzheimer’s disease (AD), both sleep and circadian dysfunctions are commonly reported and these are associated with neurodegenerative change. Actually, it has been reported that changes in circadian rhythms in AD were apparently discrete from those seen in normal aging. Previous studies reported the delayed phase in the activity or core body temperature rhythms in severe AD patients compared to normal controls. However, it is unknown whether similar changes in melatonin rhythms occur in AD patients who were not severely demented. We aimed to compare melatonin rhythms depending on dementia severity in mild and moderate AD patients. Methods We recruited AD patients of mild or moderate degree who had the Pittsburgh Sleep Quality Index (PSQI) score of 5 or greater and/or complained insomnia symptoms more than 3 times a week for a month. The patients were classified according to their Clinical Dementia Rating (CDR) score into 3 groups (CDR=0.5, 1, 2). The dim light melatonin onset (DLMO) was determined from seven hourly saliva samples obtained in the laboratory prior to sleep onset measured by actigraphy. The phase angle between the DLMO and sleep onset (PA-SO), and that between the DLMO and midsleep time (PA-MST) were calculated. Each group included 13, 13 and 6 AD patients with the CDR score of 0.5, 1 and 2, respectively. The DLMO and PA were compared among the 3 groups, and correlation analyses of the DLMO and PA with the MMSE in the Korean version of CERAD Packet (MMSE-KC) scores were done in total patients. Results There was no significant difference in the DLMO and PA between the 3 groups. The MMSE-KC score was positively correlated with the DLMO and negatively correlated with the PA-MST. Conclusion There were no changes in melatonin rhythms according to dementia severity in mild and moderate AD patients with sleep complaints. However, our study showed that earlier melatonin phase was associated with more impaired cognitive function. Support Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT &amp; Future Planning (2017R1A2B4003493)

Disrupted sleep maintenance is associated with altered circadian phase and phase angle in community-dwelling adults

ObjectiveWe aimed to compare the sleep onset, dim light melatonin onset (DLMO) and phase angle (PA) between sleep onset and DLMO of insomnia patients with those of controls, and to examine the difference in these parameters in relation to objective sleep quality. MethodsParticipants were recruited from three Public Health Centers in Korea. Actigraphy recordings were conducted for seven days. Five hourly saliva samples were obtained from three hours prior to sleep onset. A total of 48 controls and 64 insomnia patients were analyzed. Nocturnal sleep parameters, DLMO, and PA were compared between the controls and insomnia patients, and between the controls and patients with difficulty in maintaining sleep (DMS). These sleep and circadian parameters were compared among the subgroups divided by wake after sleep onset (WASO) amount. ResultsThere were no significant differences in sleep parameters between the control and insomnia groups, and between the controls and DMS subgroup. The sleep onset, DLMO, and PA of the insomnia group or those of DMS subgroup were not different from those of controls. There were significant differences in the sleep onset and DLMO (p < 0.05) among mild, moderate, and severe WASO groups. A regression analysis revealed the earlier DLMO and shorter PA predicted the severity of WASO (p < 0.0001) in total participants. ConclusionsInsomnia patients exhibited no difference in their sleep timing and melatonin rhythm compared to controls. However, these circadian parameters varied depending on the severity of WASO, and advanced melatonin phase and its shortened phase angle were associated with worsening of sleep maintenance.

Mood and sleep improvement with critically-timed wake and light interventions in premenstrual, peripartum vs. perimenopausal depression depend on specific underlying melatonin and sleep circadian phase disturbances

Mood and sleep improvement with critically-timed wake and light interventions in premenstrual, peripartum vs. perimenopausal depression depend on specific underlying melatonin and sleep circadian phase disturbances

Diurnal rhythms of cortisol and melatonin in night eating and non-night eating male police officers

Abstract Background Working during the night has in previous studies been associated with behavioural changes and diseases. Disturbance between behavioural and biological circadian rhythms have been suggested as a possible mechanism linking night work with cardiovascular diseases and pre-diabetic changes. The aim of this study was to investigate if night eating during two, four and seven consecutive night shifts is associated with differences in the diurnal rhythms of cortisol and melatonin in male police officers in Denmark. Methods We conducted an experimental study among 37 male police officers in Denmark who all collected data on the last night shift in three different work schedules with two, four and seven consecutive night shifts, respectively. Night eating was self-reported and defined as eating at least one main meal between midnight and early morning. Differences in the diurnal rhythms of concentrations of cortisol and melatonin in saliva were tested by phase changes and amplitude differences. Results Sixteen (43.2%) police officers ate a main meal during the last night shift in all three work schedules. The timing of the lowest cortisol concentration was on average delayed with 2:10 hours (95% CI 0:24-3:56 hours) and the level of the lowest cortisol concentration was on average supressed with 66% (95% CI 47-94%) for night eaters compared to non-night eaters. There was no association with number of consecutive night shifts. The phase and amplitude of melatonin were not statistically significantly different between night eaters and non-night eaters. Conclusions Night eating behaviour is associated with differences in the diurnal rhythm of cortisol in Danish male police officers working during the night. The difference in cortisol rhythm between night eaters and non-night eaters on night shifts is not affected by the number of consecutive night shifts. Key messages Night eating behaviour is associated with differences in the diurnal rhythm of cortisol. Future studies should focus on potential health outcomes of night eating behaviour among night workers.

Generalizability of A Neural Network Model for Circadian Phase Prediction in Real-World Conditions

A neural network model was previously developed to predict melatonin rhythms accurately from blue light and skin temperature recordings in individuals on a fixed sleep schedule. This study aimed to test the generalizability of the model to other sleep schedules, including rotating shift work. Ambulatory wrist blue light irradiance and skin temperature data were collected in 16 healthy individuals on fixed and habitual sleep schedules, and 28 rotating shift workers. Artificial neural network models were trained to predict the circadian rhythm of (i) salivary melatonin on a fixed sleep schedule; (ii) urinary aMT6s on both fixed and habitual sleep schedules, including shift workers on a diurnal schedule; and (iii) urinary aMT6s in rotating shift workers on a night shift schedule. To determine predicted circadian phase, center of gravity of the fitted bimodal skewed baseline cosine curve was used for melatonin, and acrophase of the cosine curve for aMT6s. On a fixed sleep schedule, the model predicted melatonin phase to within ± 1 hour in 67% and ± 1.5 hours in 100% of participants, with mean absolute error of 41 ± 32 minutes. On diurnal schedules, including shift workers, the model predicted aMT6s acrophase to within ± 1 hour in 66% and ± 2 hours in 87% of participants, with mean absolute error of 63 ± 67 minutes. On night shift schedules, the model predicted aMT6s acrophase to within ± 1 hour in 42% and ± 2 hours in 53% of participants, with mean absolute error of 143 ± 155 minutes. Prediction accuracy was similar when using either 1 (wrist) or 11 skin temperature sensor inputs. These findings demonstrate that the model can predict circadian timing to within ± 2 hours for the vast majority of individuals on diurnal schedules, using blue light and a single temperature sensor. However, this approach did not generalize to night shift conditions.

Increased sensitivity of the circadian system to light in delayed sleep-wake phase disorder.

This is the first study to demonstrate an altered circadian phase shifting response in a circadian rhythm sleep disorder. Patients with delayed sleep-wake phase disorder (DSWPD) demonstrate greater sensitivity of the circadian system to the phase-delaying effects of light. Increased circadian sensitivity to light is associated with later circadian timing within both control and DSWPD groups. DSWPD patients had a greater sustained pupil response after light exposure. Treatments for DSWPD should consider sensitivity of the circadian system to light as a potential underlying vulnerability, making patients susceptible to relapse. Patients with delayed sleep-wake phase disorder (DSWPD) exhibit delayed sleep-wake behaviour relative to desired bedtime, often leading to chronic sleep restriction and daytime dysfunction. The majority of DSWPD patients also display delayed circadian timing in the melatonin rhythm. Hypersensitivity of the circadian system to phase-delaying light is a plausible physiological basis for DSWPD vulnerability. We compared the phase shifting response to a 6.5h light exposure (∼150lux) between male patients with diagnosed DSWPD (n=10; aged 20.8±2.3years) and male healthy controls (n=11; aged 22.4±3.3years). Salivary dim light melatonin onset (DLMO) was measured under controlled conditions in dim light (<3lux) before and after light exposure. Correcting for the circadian time of the light exposure, DSWPD patients exhibited 31.5% greater phase delay shifts than healthy controls. In both groups, a later initial melatonin phase was associated with a greater magnitude phase shift, indicating that increased circadian sensitivity to light may be a factor that contributes to delayed phase, even in non-clinical groups. DSWPD patients also had reduced pupil size following the light exposure, and showed a trend towards increased melatonin suppression during light exposure. These findings indicate that, for patients with DSWPD, assessment of light sensitivity may be an important factor that can inform behavioural therapy, including minimization of exposure to phase-delaying night-time light.

Average mid-sleep time as a proxy for circadian phase.

Assessments of circadian phase using melatonin are laborious. Sleep-time indices allow for less laborious phase calculations, but common indices weakly represent melatonin phase. We show how a single sleep-time assessment can represent melatonin phase by over 60%, improving the use of subjective sleep to mirror objective circadian phase.