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Numerous studies have reported that eveningness is associated with increased alcohol consumption. However, biological markers of circadian timing, such as dim light melatonin onset (DLMO) and circadian photoreceptor responsivity (post-illumination pupil response, PIPR), have rarely been assessed in the context of habitual alcohol consumption. This study aimed to examine sleep, circadian timing, and photoreceptor responsivity in adult alcohol drinkers.Participants (21 to 45 years) included 28 light and 50 heavy drinkers. The 8-day study consisted of a week of ad lib sleep monitored with wrist actigraphy, followed by a 9-h laboratory session with a photoreceptor responsivity and circadian phase assessment.The heavy drinkers obtained on average 28 more minutes of sleep (p = 0.002) and reported more eveningness than the light drinkers (p = 0.029). There was a trend for a shorter DLMO-midsleep interval (p = 0.059) in the heavy drinkers, reflecting a tendency for them to sleep at an earlier circadian phase. The PIPR in the heavy drinkers was significantly smaller than in the light drinkers (p = 0.032), suggesting reduced circadian photoreceptor responsivity in the heavy drinkers. A larger PIPR was significantly associated with a later DLMO in the light drinkers (r = 0.44, p = 0.019), but this relationship was absent in the heavy drinkers (r = -0.01, p = 0.94).These results are consistent with earlier reports of more eveningness and a shorter DLMO-midsleep interval being associated with heavier alcohol drinking. The novel finding of reduced circadian photoreceptor responsivity in heavy drinkers is consistent with prior rodent studies. Future studies should explore the impact of habitual alcohol consumption on other measures of circadian photoreceptor responsivity.

Daily rhythms are observed in humans and almost all other organisms. Most of these observed rhythms reflect both underlying endogenous circadian rhythms and evoked responses from behaviours such as sleep/wake, eating/fasting, rest/activity, posture changes and exercise. For many research and clinical purposes, it is important to understand the contribution of the endogenous circadian component to these observed rhythms.The goal of this manuscript is to provide guidance on best practices in measuring metrics of endogenous circadian rhythms in humans and promote the inclusion of circadian rhythms assessments in studies of health and disease. Circadian rhythms affect all aspects of physiology. By specifying minimal experimental conditions for studies, we aim to improve the quality, reliability and interpretability of research into circadian and daily (i.e., time-of-day) rhythms and facilitate the interpretation of clinical and translational findings within the context of human circadian rhythms. We describe protocols, variables and analyses commonly used for studying human daily rhythms, including how to assess the relative contributions of the endogenous circadian system and other daily patterns in behaviours or the environment. We conclude with recommendations for protocols, variables, analyses, definitions and examples of circadian terminology.Although circadian rhythms and daily effects on health outcomes can be challenging to distinguish in practice, this distinction may be important in many clinical settings. Identifying and targeting the appropriate underlying (patho)physiology is a medical goal. This review provides methods for identifying circadian effects to aid in the interpretation of published work and the inclusion of circadian factors in clinical research and practice.

BACKGROUND: Sleep disturbance is common among individuals with Tourette’s Disorder (TD). Given that sleep is influenced by the circadian system, this study examined circadian rhythms and sleep in adults with TD, and explored the possible benefit of short-wavelength wearable morning light therapy. METHODS: Participants were 34 adults with TD (n=14) and age- and sex-matched healthy controls (HC; n=20). Participants were screened using clinician-rated diagnostic and tic severity interviews, and procedures lasted 3 consecutive weeks. Participants completed a baseline week of actigraphy. Adults with TD completed two weeks of Re-Timer(™) morning light therapy and continued actigraphy monitoring. Dim light melatonin onset (DLMO) phase assessment, tic severity interview, and measures of chronotype, sleep disturbance, daytime sleepiness, disability, depression, anxiety, and stress were completed at baseline and post-intervention. RESULTS: Adults with TD reported significantly greater eveningness and sleep disturbance relative to controls. Per wrist actigraphy, adults with TD exhibited significantly longer sleep onset latency, lower sleep efficiency, and greater sleep fragmentation than HC. Following morning light therapy there was significant advances in DLMO phase, but not self-report or actigraphy sleep variables. There were small, statistically significant decreases in tic severity and impairment. There were also significant reductions in daytime sleepiness, and self-reported anxiety, but not depression, stress, or disability. Participants reported minimal side effects and rated light therapy as acceptable and comfortable. CONCLUSIONS: Findings showed some benefits following brief light therapy in TD; further exploration of the impact of spectral tuning the photic environment as part of treatment for TD subjects is warranted.

Background There is increasing evidence that bipolar disorder is influenced by circadian timing, including the timing of sleep and waking activities. Previous studies in bipolar disorder have shown that people with later timed daily activities, also known as late chronotypes, are at higher risk for subsequent mood episodes over the following 12–18 months. However, these studies were limited to euthymic patients and smaller sample sizes. The aim of the current study was to further examine baseline chronotype as a potentially important predictor of mood-related outcomes in a larger sample of individuals with bipolar disorder and over the longest follow up period to date, of 5 years. Participants included 318 adults diagnosed with bipolar I and II (19–86 years) who were enrolled in the Prechter Longitudinal Study of Bipolar Disorder. Results Participants with a late chronotype were found to be more likely to have mild to more severe depressive symptoms (PHQ-9 ≥ 5) as captured with PHQ-9 assessments every 2 months over the 5 year follow up period. This higher risk for depressive symptoms remained even after adjusting for age, sex and mood at baseline. Additionally, late chronotypes reported fewer hypomania/mania episodes during the 5 year follow up, as derived from clinical interviews every two years. Conclusions These results highlight the potential clinical usefulness of a single self-report question, in identifying patients at risk for a more depressive mood course. The results also suggest that circadian phase advancing treatments, that can shift circadian timing earlier, should be explored as a means to reduce depressive symptoms in late chronotypes with bipolar disorder.

Light is a potent circadian entraining agent. For many people, daily light exposure is fundamentally dysregulated with reduced light during the day and increased light into the late evening. This lighting schedule promotes chronic disruption to circadian physiology resulting in a myriad of impairments. Developmental changes in sleep-wake physiology suggest that such light exposure patterns may be particularly disruptive for adolescents and further compounded by lifestyle factors such as early school start times. This narrative review describes evidence that reduced light exposure during the school day delays the circadian clock, and longer exposure durations to light-emitting electronic devices in the evening suppress melatonin. While home lighting in the evening can suppress melatonin secretion and delay circadian phase, the patterning of light exposure across the day and evening can have moderating effects. Photic countermeasures may be flexibly and scalably implemented to support sleep-wake health; including manipulations of light intensity, spectra, duration and delivery modality across multiple contexts. An integrative approach addressing physiology, attitudes, and behaviors will support optimization of light-driven sleep-wake outcomes in adolescents.

This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep–wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time. While there are incomplete and insufficient prevalence data, CRSWD likely affect at least 800,000 and perhaps as many as 3 million individuals in the United States, and if Shift Work Disorder and Jet Lag are included, then many millions more are impacted. The SRS Advocacy Taskforce has identified CRSWD as a class of sleep disorders for which additional high-quality research could have a significant impact to improve patient care. Participants were selected for their expertise and were assigned to one of three working groups: Phase Disorders, Entrainment Disorders, and Other. Each working group presented a summary of the current state of the science for their specific CRSWD area, followed by discussion from all participants. The outcome of those presentations and discussions are presented here.

Study ObjectivesA critical barrier to successful treatment of circadian misalignment in shift workers is determining circadian phase in a clinical or field setting. Light and movement data collected passively from wrist actigraphy can generate predictions of circadian phase via mathematical models; however, these models have largely been tested in non-shift working adults. This study tested the feasibility and accuracy of actigraphy in predicting dim light melatonin onset (DLMO) in fixed night shift workers.MethodsA sample of 45 night shift workers wore wrist actigraphs before completing DLMO in the laboratory (17.0 days ± 10.3 SD). DLMO was assessed via 24 hourly saliva samples in dim light (ResultsModel predictions of DLMO showed good concordance with in-lab DLMO, with Lin’s concordance coefficient of 0.70, which was twice as high as agreement using average sleep timing as a proxy of DLMO. The absolute mean error of the predictions was 2.88 h, with 76% and 91% of the predictions falling with 2 and 4 h, respectively.ConclusionThis study is the first to demonstrate the use of wrist actigraphy-based estimates of circadian phase as a clinically useful and valid alternative to in-lab measurement of DLMO in fixed night shift workers. Future research should explore how additional predictors may impact accuracy.

Study Objectives We investigated biological and behavioral rhythm period lengths (i.e. taus) of delayed sleep–wake phase disorder (DSWPD) and non-24-hour sleep–wake rhythm disorder (N24SWD). Based on circadian phase timing (temperature and dim light melatonin onset), DSWPD participants were dichotomized into a circadian-delayed and a circadian non-delayed group to investigate etiological differences. Methods Participants with DSWPD (n = 26, 17 m, age: 21.85 ± 4.97 years), full-sighted N24SWD (n = 4, 3 m, age: 25.75 ± 4.99 years) and 18 controls (10 m, age: 23.72 ± 5.10 years) participated in an 80-h modified constant routine. An ultradian protocol of 1-h “days” in dim light, controlled conditions alternated 20-min sleep/dark periods with 40-min enforced wakefulness/light. Subjective sleepiness ratings were recorded prior to every sleep/dark opportunity and median reaction time (vigilance) was measured hourly. Obtained sleep (sleep propensity) was derived from 20-min sleep/dark opportunities to quantify hourly objective sleepiness. Hourly core body temperature was recorded, and salivary melatonin assayed to measure endogenous circadian rhythms. Rhythm data were curved using the two-component cosine model. Results Patients with DSWPD and N24SWD had significantly longer melatonin and temperature taus compared to controls. Circadian non-delayed DSWPD had normally timed temperature and melatonin rhythms but were typically sleeping at relatively late circadian phases compared to those with circadian-delayed DSWPD. Conclusions People with DSWPD and N24SWD exhibit significantly longer biological circadian rhythm period lengths compared to controls. Approximately half of those diagnosed with DSWPD do not have abnormally delayed circadian rhythm timings suggesting abnormal phase relationship between biological rhythms and behavioral sleep period or potentially conditioned sleep-onset insomnia.

Adult studies show that healthy diet patterns relate to better sleep. However, evidence during adolescence, when sleep may change dramatically, is lacking. Within a cohort of 458 Mexican adolescents, we examined whether consumption of three dietary patterns was associated with sleep duration and timing measured 2 years later, as well as changes in sleep timing and duration. Dietary patterns (identified a posteriori in a prior analysis) were assessed with a baseline food frequency questionnaire, and sleep was measured with wrist actigraphy at baseline and follow-up. Linear regression analyses adjusting for sex, age, screen time, and smoking were conducted. Adolescents with higher consumption of a Plant-Based and Lean Proteins pattern had earlier sleep timing (&minus, 0.45 h with 95% Confidence Interval (CI) &minus, 0.81, &minus, 0.08 in the highest compared to lowest quartiles), less of a phase delay in sleep timing over follow-up (&minus, 0.39 h with 95% CI &minus, 0.80, 0.02), and shorter weekend sleep duration (0.5 h with 95% CI &minus, 0.88, &minus, 0.1). Higher consumption of an Eggs, Milk and Refined Grain pattern was associated with earlier sleep timing (&minus, 0.40 h with 95% CI &minus, 0.77, &minus, 0.04), while consumption of a Meat and Starchy pattern was related to higher social jetlag (weekend&ndash, weekday sleep timing difference). Healthier diet patterns may promote better sleep in adolescents.

In addition to the caloric and macronutrient composition of meals, timing of energy consumption may be important for optimal glucose metabolism. Our goal was to examine whether the habitual timing of energy intake was associated with insulin sensitivity in healthy volunteers. Volunteers without diabetes aged 21&ndash, 50 years completed a 3-day food diary and underwent an oral glucose tolerance test to estimate insulin sensitivity (n = 44). From the food diary, we calculated the proportions of the total energy and macronutrients consumed in the morning and evening, and the clock time at which 25%, 50% and 75% of total energy was consumed. A greater proportion of energy intake in the morning was significantly associated with higher insulin sensitivity estimated by Matsuda Index (B = 2.8 per 10%, 95%CI: 0.3, 5.2). The time at which 25% of energy was consumed was associated with insulin sensitivity estimated by Matsuda Index (B = &minus, 1.6 per hour, 95%CI: &minus, 3.0, &minus, 0.3) and QUICKI (B = &minus, 1.4 per hour, 95%CI: &minus, 2.8, &minus, 0.1). The timing of carbohydrate consumption demonstrated similar associations. Greater energy intake earlier in the day was associated with higher insulin sensitivity in individuals without diabetes.

Irregular rest-activity patterns can disrupt metabolic and hormonal physiology and potentially lead to disease. Little is known regarding rest-activity patterns during gestation and their association with hormonal rhythms and health in pregnant women. We conducted a pilot study to determine if 24 h rest-activity was related to saliva cortisol rhythms and maternal-fetal health in an economically disadvantaged population. Primiparous women wore a wrist actigraphy device for a week to record activity during gestational weeks 22 (G22; n = 50) and 32 (G32; n = 46) and postpartum week one (PPW1; n = 39). Participants collected saliva samples every 4 hr over a 24 hr period during G22 (n = 22), G32 (n = 20) and 24–48 hr postnatal (n = 20), and cortisol concentrations were measured with ELISA. Circadian rhythmicity was assessed using autocorrelation coefficient (r24) and cosinor analysis. Blood glucose levels, body mass index (BMI), gestational disease data, and gestational age of infant at birth were abstracted from medical charts. Time of cortisol peak (acrophase) during G22 was related with acrophase of activity (r = 0.66; p = 0.001) and blood glucose levels (r = 0.58; p = 0.006). During G22, minutes of wake after sleep onset was positively related to cortisol mesor and AUC (p

OBJECTIVE: To examine the feasibility, acceptability, and effects of a home-based morning bright light treatment on pain, mood, sleep, and circadian timing in US veterans with chronic low back pain. DESIGN: An open treatment trial with a seven-day baseline, followed by 13 days of a one-hour morning bright light treatment self-administered at home. Pain, pain sensitivity, mood, sleep, and circadian timing were assessed before, during, and after treatment. SETTING: Participants slept at home, with weekly study visits and home saliva collections. PARTICIPANTS: Thirty-seven US veterans with medically verified chronic low back pain. METHODS: Pain, mood, and sleep quality were assessed with questionnaires. Pain sensitivity was assessed using two laboratory tasks: a heat stimulus and an ischemia stimulus that gave measures of threshold and tolerance. Sleep was objectively assessed with wrist actigraphy. Circadian timing was assessed with the dim light melatonin onset. RESULTS: Morning bright light treatment led to reduced pain intensity, pain behavior, thermal pain threshold sensitivity, post-traumatic stress disorder symptoms, and improved sleep quality (P

ᅟ The Morningness-Eveningness Questionnaire (MEQ) and Munich ChronoType Questionnaire (MCTQ) are sometimes used to estimate circadian timing. However, it remains unclear if they can reflect a change in circadian timing after a light treatment. In this study, 31 participants (25–68 years) completed both questionnaires before and after a 13–28 day morning light treatment. The dim light melatonin onset (DLMO), a physiological marker of circadian timing, was also assessed in a subsample of 16 participants. The DLMO phase advanced on average by 47 min (p

This article focuses on melatonin and other melatonin receptor agonists, and specifically their circadian phase shifting and sleep-enhancing properties. The circadian system and circadian rhythm sleep-wake disorders are briefly reviewed, followed by a summary of the circadian phase shifting, sleep-enhancing properties, and possible safety concerns associated with melatonin and other melatonin receptor agonists. The recommended use of melatonin, including dose and timing, in the latest American Academy of Sleep Medicine Clinical Practice Guidelines for the treatment of intrinsic circadian rhythm disorders is also reviewed. Lastly, the practical aspects of treatment and consideration of clinical treatment outcomes are discussed.

Objective This observational pilot study examined objective circadian phase and sleep timing in chronic migraine (CM) and healthy controls (HC) and the impact of circadian factors on migraine frequency and severity. Background Sleep disturbance has been identified as a risk factor in the development and maintenance of CM but the biological mechanisms linking sleep and migraine remain largely theoretical. Methods Twenty women with CM and 20 age-matched HC completed a protocol that included a 7 day sleep assessment at home using wrist actigraphy followed by a circadian phase assessment using salivary melatonin. We compared CM vs HC on sleep parameters and circadian factors. Subsequently, we examined associations between dim-light melatonin onset (DLMO), the midpoint of the sleep episode, and the phase angle (time from DLMO to sleep midpoint) with the number of migraine days per month and the migraine disability assessment scale (MIDAS). Results CM and HC did not differ on measures of sleep or circadian phase. Within the CM group, more frequent migraine days per month was significantly correlated with DLMO (r = .49, P = .039) and later sleep episode (r = .47, P = .037). In addition, a greater phase angle (ie, circadian misalignment) was significantly correlated with more severe migraine-related disability (r = .48, P = .042). These relationships remained significant after adjusting for total sleep time. Conclusions This pilot study revealed that circadian misalignment and delayed sleep timing are associated with higher migraine frequency and severity, which was not better accounted for by the amount of sleep. These findings support the plausibility and need for further investigation of a circadian pathway in the development and maintenance of chronic headaches. Specifically, circadian misalignment and delayed sleep timing could serve as an exacerbating factor in chronic migraines when combined with biological predispositions or environmental factors.

Study Objectives:Recent evidence indicates that daytime sleep disturbance associated with night shift work may arise from both circadian misalignment and sleep reactivity to stress. This presents a...

There is increasing evidence that sleep and circadian disruption can worsen the disease course in inflammatory bowel disease (IBD). Sleep and circadian disruption are prevalent in society and are associated with worse outcomes in IBD. Emerging research suggests sleep and circadian disruption can impact key components in IBD disease flares, including intestinal permeability, translocation of bacterial endotoxins, intestinal dysbiosis, and proinflammatory cytokines. Much of this research has been conducted in animal models. There is a clear need for large randomized controlled trials in human patients with IBD, where the potential for chronotherapeutic strategies to improve disease course can be tested.

Few studies have examined relationships between circadian rhythms and unipolar major depressive disorder. Further, no study to date has examined circadian markers as predictors of response to depression treatment. In the present study, we examined associations between circadian timing and its alignment with sleep and depression severity in 30 adults with major depressive disorder who completed a randomized controlled trial of two weeks of time in bed (TIB) restriction administered adjunctive to fluoxetine, with a focus on sex differences. Thirty adults with major depressive disorder received 8 weeks of fluoxetine 20–40 mgs and were randomized to 8h TIB or 6h TIB for the first 2 weeks. Participants in the 6h TIB condition were further randomized to a delayed bedtime or advanced risetime group. Circadian measures included dim light melatonin onset (DLMO) and the difference between DLMO and midsleep point (i.e., phase angle difference). Depression was assessed using the Hamilton Rating Scale for Depression. For females, a phase delay after 2 weeks of fluoxetine and the experimental TIB manipulation was associated with a poorer response to fluoxetine, and depression severity was negatively correlated with phase angle difference, whereas males showed a positive correlation between depression severity and phase angle difference.

Objective/Background To compare sleep and circadian variability in adults with delayed sleep–wake phase disorder (DSWPD) to healthy controls. Patients/Methods Forty participants (22 DSWPD, 18 healthy controls) completed a ten-day protocol, consisting of DLMO assessments on two consecutive nights, a five-day study break, followed by two more DLMO assessments. All participants were instructed to sleep within one hour of their self-reported average sleep schedule for the last four days of the study break. We analyzed the participants' wrist actigraphy data during these four days to examine intraindividual variability in sleep timing, duration and efficiency. We also examined shifts in the DLMO from before and after the study break. Results and conclusions Under the same conditions, people with DSWPD had significantly more variable wake times and total sleep time than healthy controls (p ≤ 0.015). Intraindividual variability in sleep onset time and sleep efficiency was similar between the two groups (p ≥ 0.30). The DLMO was relatively stable across the study break, with only 11% of controls but 27% of DSWPDs showed more than a one hour shift in the DLMO. Only in the DSWPD sample was greater sleep variability associated with a larger shift in the DLMO (r = 0.46, p = 0.03). These results suggest that intraindividual variability in sleep can be higher in DSWPD versus healthy controls, and this may impact variability in the DLMO. DSWPD patients with higher intraindividual variability in sleep are more likely to have a shifting DLMO, which could impact sleep symptoms and the optimal timing of light and/or melatonin treatment for DSWPD. Clinical trial Circadian Phase Assessments at Home, http://clinicaltrials.gov/show/NCT01487252 , NCT01487252 .

Introduction Critically ill patients often suffer from fragmented sleep due to light and noise in the intensive care unit (ICU). We investigated whether placing patients in a sleep/circadian friendly protocol improved patient-reported sleep quality and ICU outcomes. Methods Patients were included if they were expected to have a >24-hour stay. Exclusion criteria included age Results Sixty-one patients were enrolled: 28 randomized to sleep/circadian protocol, 33 to control protocol. 14 subjects were excluded from analysis due to developing criteria for exclusion. Nine patients (median age 50 years, 6 females) maintained in the sleep/circadian protocol, 13 patients were not maintained in sleep/circadian protocol and 25 patients in control protocol (median age 64 years, 20 females). There was no difference in age, gender, or race between groups (p> 0.05). Median ICU first overnight dB level (10:00pm-6:00am) was 44.2 (±2.7) for sleep/circadian protocol and 50.5 (±4.9) for combined group (p= 0.008). Median ICU first overnight lux (10:00pm-4:00am) was 2.28 (±61.3) in sleep/circadian protocol and 18.42 (±90.9) in combined group (p=0.0374). A continued stay in the sleep/circadian protocol resulted in decreased total decibel level (p= 0.0018) decreased total overnight lux exposure (p= 0.0025) and decreased reported awakenings in first night (p= 0.0175). There were no differences in ICU length of stay, inpatient mortality, or readmission rates between groups (p>0.05). Three patients developed delirium, all originally randomized to control group. Conclusion We report on the successful outcomes associated with a sleep/circadian friendly protocol within a large tertiary center medical ICU which resulted in significant decreases in objectively assessed noise and light, and subjectively reported nocturnal awakenings. We continue to collect data to determine if the sleep/circadian friendly protocol should be permanently implemented in the ICU. Support None.

From smart work scheduling to optimal drug timing, there is enormous potential in translating circadian rhythms research results for precision medicine in the real world. However, the pursuit of such effort requires the ability to accurately estimate circadian phase outside of the laboratory. One approach is to predict circadian phase noninvasively using light and activity measurements and mathematical models of the human circadian clock. Most mathematical models take light as an input and predict the effect of light on the human circadian system. However, consumer-grade wearables that are already owned by millions of individuals record activity instead of light, which prompts an evaluation of the accuracy of predicting circadian phase using motion alone. Here, we evaluate the ability of four different models of the human circadian clock to estimate circadian phase from data acquired by wrist-worn wearable devices. Multiple datasets across populations with varying degrees of circadian disruption were used for generalizability. Though the models we test yield similar predictions, analysis of data from 27 shift workers with high levels of circadian disruption shows that activity, which is recorded in almost every wearable device, is better at predicting circadian phase than measured light levels from wrist-worn devices when processed by mathematical models. In those living under normal living conditions, circadian phase can typically be predicted to within 1 h, even with data from a widely available commercial device (the Apple Watch). These results show that circadian phase can be predicted using existing data passively collected by millions of individuals with comparable accuracy to much more invasive and expensive methods.

The preference of the sleep/wake cycle can be grouped into categories or chronotypes. Inflammatory bowel disease (IBD) has been linked to poor sleep quality which correlates with disease severity. Social jet lag (SJL) is the difference between sleep timing on work and free days and is a marker for circadian misalignment which has been linked to increased inflammation. We investigated whether chronotype, SJL, sleep debt (SD), and food timing were associated with an IBD specific complications and a lower quality of life. Overall, 191 subjects (115 IBD subjects and 76 healthy controls (HC)) completed the Pittsburgh Sleep Quality Index (PSQI), Morningness-Eveningness Questionnaire (MEQ), Munich ChronoType Questionnaire (MCTQ), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and a structured Food Timing Questionnaire. Later chronotype (by MEQ) was associated with a worse SIBDQ (r = -0.209; P 0.05). SJL was increased in IBD at 1.32 h ± 1.03 vs. 1.05 h ± 0.97 in HC, P 0.05, when adjusted for age. SJL (2 h) was present in 40% of severe/complicated Crohn's patients (fistulizing or structuring Crohn's or history of Crohn's related surgery) compared to only 16% of uncomplicated Crohn's patients (P 0.05). Sleep debt was increased in IBD subjects compared to HC at 21.90 m ± 25.37 vs. 11.49 m ± 13.58, P 0.05. IBD subjects with inconsistent breakfast or dinner times had lower SIBDQ scores (4.78 ± 1.28 vs. 5.49 ± 1.02, P 0.05; 4.95 ± 0.31 vs. 5.42 ± 0.32, P 0.05 respectively). In summary, later chronotype, and markers of circadian misalignment (social jet lag, sleep debt, and inconsistent meal timing) were associated with IBD disease specific complications and/or lower quality of life.

The dim light melatonin onset (DLMO) is the most reliable measure of central circadian timing in humans. However, it is not always possible to measure the DLMO because sample collection has to occur in the hours before usual sleep onset, it requires staff support and considerable participant effort, and it is relatively expensive. Questionnaires that ask people about the timing of their behavior, such as their sleep, may provide an easier and less expensive estimate of circadian timing. The objective of this analysis was to compare the MEQ score derived from the Morningness-Eveningness Questionnaire (MEQ) and the MSFsc derived from the Munich ChronoType Questionnaire (MCTQ) to the DLMO in the largest sample to date ( N = 60). Our hypothesis was that MSFsc would correlate more highly with the DLMO than MEQ score. Our sample of 36 healthy controls and 24 patients with delayed sleep phase disorder ranged in age from 18 to 62 years. All participants slept at times of their own choosing for a week before the assessment of their DLMO. The DLMO correlated significantly with both the MEQ score ( r = −0.70, p < 0.001) and MSFsc ( r = 0.68, p < 0.001). A linear regression using MEQ, MSFsc, and age to predict the DLMO explained 60% of the DLMO variance. The strongest predictor of the DLMO was MSFsc (beta = 0.51, p = 0.001), followed by MEQ (beta = −0.41, p = 0.004), and age (beta = 0.26, p = 0.013). The beta values for MSFsc and MEQ score were not statistically different from each other. Nonetheless, around a 4-h range in the DLMO was observed at a given MEQ score and a given MSFsc, indicating that neither questionnaire should be exclusively used to time light or exogenous melatonin treatment, as this could result in the mistiming of these treatments relative to the DLMO, thereby potentially worsening circadian misalignment.

A significant delay in the timing of endogenous circadian rhythms has been associated with delayed sleep phase disorder (DSPD). More recently, other mechanisms have also been proposed to account for this disorder. To further explore the etiology of DSPD, the present study compared nocturnal melatonin profiles of 26 DSPD patients (18 males, 8 females; age, 21.73 ± 4.98 years) and 17 normally timed good sleepers (10 males, 7 females; age, 23.82 ± 5.23 years) in a time-free, dim-light (

Chronic heavy alcohol use is known to cause gut leakiness and alcoholic liver disease (ALD), but only 30% of heavy drinkers develop increased intestinal permeability and ALD. The hypothesis of this study was that disruption of circadian rhythms is a potential risk factor in actively drinking alcoholics for gut leakiness and endotoxemia. We studied 20 subjects with alcohol use disorder (AD) and 17 healthy controls (HC, 6 day workers, 11 night workers). Subjects wore a wrist actiwatch for 7 days and underwent a 24-h dim light phase assessment and urine collection for intestinal permeability. The AD group had significantly less total sleep time and increased fragmentation of sleep ( P < 0.05). AD also had significantly lower plasma melatonin levels compared with the HC [mean area under the curve (AUC) 322.78 ± 228.21 vs. 568.75 ± 304.26 pg/ml, P = 0.03]. In the AD group, AUC of melatonin was inversely correlated with small bowel and colonic intestinal permeability (lactulose-to-mannitol ratio, r = −0.39, P = 0.03; urinary sucralose, r = −0.47, P = 0.01). Cosinor analysis of lipopolysaccharide-binding protein (marker of endotoxemia) and lipopolysaccharide every 4 h for 24 h in HC and AD subjects had a midline estimating statistic of rhythm of 5,026.15 ± 409.56 vs. 6,818.02 ± 628.78 ng/ml ( P < 0.01) and 0.09 ± 0.03 vs. 0.15 ± 0.19 EU/ml ( P < 0.05), respectively. We found plasma melatonin was significantly lower in the AD group, and lower melatonin levels correlated with increased intestinal permeability and a marker of endotoxemia. Our study suggests the suppression of melatonin in AD may promote gut leakiness and endotoxemia.

Little is known about the light exposure in full-time office workers, who spend much of their workdays indoors. We examined the 24-hour light exposure patterns of 14 full-time office workers during a week in summer, and assessed their dim light melatonin onset (DLMO, a marker of circadian timing) at the end of the working week. Six workers repeated the study in winter. Season had little impact on the workers' schedules, as the timing of sleep, commute, and work did not vary by more than 30 minutes in the summer and winter. In both seasons, workers received significantly more morning light on workdays than weekends, due to earlier wake times and the morning commute. Evening light in the two hours before bedtime was consistently dim. The timing of the DLMO did not vary between season, and by the end of the working week, the workers slept at a normal circadian phase.

We sought to establish the feasibility and preliminary effects of home-wearable light therapy for postpartum depression, and its effects on circadian measures. Eight women within 6 months postpartum were prescribed 60 min of daily morning light therapy for 5 weeks. The device was well tolerated. Significant improvements were observed in self-report and clinician-rated depression symptoms, with little change in objective circadian measures. Home-wearable light therapy is feasible for postpartum women and may be a promising treatment for postpartum depression. Clinicaltrials.gov Identifier: NCT02769858

This review summarizes recent developments relevant to the treatment of circadian rhythm sleep-wake disorders. The clinical practice guidelines for the treatment of intrinsic circadian rhythm sleep-wake disorders is described, followed by recent treatment studies for delayed sleep-wake phase disorder, non-24 hour sleep-wake disorder, irregular sleep-wake disorder and shift work. New methods to estimate circadian phase, including home saliva collection to estimate the dim light melatonin onset, circadian questionnaires and general rules to guide light and exogenous melatonin treatments are described. New developments in light treatment are detailed, including light flashes during sleep and wearable light devices. Substances such as caffeine and alcohol, and devices such as electronic tablets are also considered for their potential to shift circadian timing. Finally, an update on melatonin supplements in the US is discussed, along with the controversy surrounding the use of melatonin supplements in patients with prediabetes or diabetes.

The efficacy of bright light and/or melatonin treatment for Delayed Sleep Wake Phase Disorder (DSWPD) is contingent upon an accurate clinical assessment of the circadian phase. However, the process of determining this circadian phase can be costly and is not yet readily available in the clinical setting. The present study investigated whether more cost-effective and convenient estimates of the circadian phase, such as self-reported sleep timing, can be used to predict the circadian phase and guide the timing of light and/or melatonin treatment (i.e. dim-light melatonin onset, core body temperature minimum and melatonin secretion mid-point) in a sample of individuals with DSWPD.Twenty-four individuals (male = 17; mean age = 21.96, SD = 5.11) with DSWPD were selected on the basis of ICSD-3 criteria from a community-based sample. The first 24-hours of a longer 80-hour constant laboratory ultradian routine were used to determine core body temperature minimum (cBTSignificant moderate to strong positive correlations were observed between self-reported sleep timing variables and DLMO, cBTThese findings suggest that self-reported sleep timing may be useful clinically to predict a therapeutically relevant circadian phase in DSWPD.

Our objectives were to investigate the period lengths (i.e., taus) of the endogenous core body temperature rhythm and melatonin rhythm in delayed sleep-wake phase disorder patients (DSWPD) and non-24-h sleep-wake rhythm disorder patients (N24SWD) compared with normally entrained individuals. Circadian rhythms were measured during an 80-h ultradian modified constant routine consisting of 80 ultrashort 1-h “days” in which participants had 20-min sleep opportunities alternating with 40 min of enforced wakefulness. We recruited a community-based sample of 26 DSWPD patients who met diagnostic criteria (17 males, 9 females; age, 21.85 ± 4.97 years) and 18 healthy controls (10 males, 8 females; age, 23.72 ± 5.10 years). Additionally, 4 full-sighted patients (3 males, 1 female; age, 25.75 ± 4.99 years) were diagnosed with N24SWD and included as a discrete study group. Ingestible core temperature capsules were used to record minute temperatures that were averaged to obtain 80 hourly data points. Salivary melatonin concentration was assessed every half-hour to determine time of dim light melatonin onset at the beginning and end of the 80-h protocol. DSWPD patients had significantly longer melatonin rhythm taus (24 h 34 min ± 17 min) than controls (24 h 22 min ± 15 min, p = 0.03, d = 0.70). These results were further supported by longer temperature rhythm taus in DSWPD patients (24 h 34 min ± 26 min) relative to controls (24 h 13 min ± 15 min, p = 0.01, d = 0.80). N24SWD patients had even longer melatonin (25 h ± 19 min) and temperature (24 h 52 min ± 17 min) taus than both DSWPD ( p = 0.007, p = 0.06) and control participants ( p < 0.001, p = 0.02, respectively). Between 12% and 19% of the variance in DSWPD patients’ sleep timing could be explained by longer taus. This indicates that longer taus of circadian rhythms may contribute to the DSWPD patients’ persistent tendency to delay, their frequent failure to respond to treatment, and their relapse following treatment. Additionally, other factors can contribute to misalignments in DSWPD and N24SWD disorders.

Alcohol-induced intestinal hyperpermeability (AIHP) is a known risk factor for alcoholic liver disease (ALD), but only 20–30% of heavy alcoholics develop AIHP and ALD. The hypothesis of this study is that circadian misalignment would promote AIHP. We studied two groups of healthy subjects on a stable work schedule for 3 mo [day workers (DW) and night workers (NW)]. Subjects underwent two circadian phase assessments with sugar challenge to access intestinal permeability between which they drank 0.5 g/kg alcohol daily for 7 days. Sleep architecture by actigraphy did not differ at baseline or after alcohol between either group. After alcohol, the dim light melatonin onset (DLMO) in the DW group did not change significantly, but in the NW group there was a significant 2-h phase delay. Both the NW and DW groups had no change in small bowel permeability with alcohol, but only in the NW group was there an increase in colonic and whole gut permeability. A lower area under the curve of melatonin inversely correlated with increased colonic permeability. Alcohol also altered peripheral clock gene amplitude of peripheral blood mononuclear cells in CLOCK, BMAL, PER1, CRY1, and CRY2 in both groups, and inflammatory markers lipopolysaccharide-binding protein, LPS, and IL-6 had an elevated mesor at baseline in NW vs. DW and became arrhythmic with alcohol consumption. Together, our data suggest that central circadian misalignment is a previously unappreciated risk factor for AIHP and that night workers may be at increased risk for developing liver injury with alcohol consumption.

Central circadian timing influences mental and physical health. Research in nocturnal rodents has demonstrated that when alcohol is consumed, it reaches the central hypothalamic circadian pacemaker (suprachiasmatic nuclei) and can directly alter circadian phase shifts to light. In two separate studies, we examined, for the first time, the effects of a single dose of alcohol on circadian phase advances and phase delays to light in humans. Two 23-day within-subjects placebo-controlled counterbalanced design studies were conducted. Both studies consisted of 6 days of fixed baseline sleep to stabilize circadian timing, a 2-day laboratory session, a 6-day break, and a repeat of 6 days of fixed sleep and a 2-day laboratory session. In the phase advance study ( n = 10 light drinkers, 24–45 yr), the laboratory sessions consisted of a baseline dim light phase assessment, sleep episode, alcohol (0.6 g/kg) or placebo, 2-h morning bright light pulse, and final phase assessment. In the phase-delay study ( n = 14 light drinkers, 22–44 yr), the laboratory sessions consisted of a baseline phase assessment, alcohol (0.8 g/kg) or placebo, 2-h late night bright light pulse, sleep episode, and final phase assessment. In both studies, alcohol either increased or decreased the observed phase shifts to light (interaction P ≥ 0.46), but the effect of alcohol vs. placebo on phase shifts to light was always on average smaller than 30 min. Thus, no meaningful effects of a single dose of alcohol vs. placebo on circadian phase shifts to light in humans were observed.

Summary Short sleep/dark durations are common in modern society. We investigated if exposure to additional evening ambient light, often associated with later bedtimes and short sleep, reduces circadian phase advances to morning bright light. Twelve healthy subjects participated in two conditions that differed in the distribution of sleep before exposure to morning bright light. Subjects had a consolidated 9-h night time sleep opportunity, or a 3-h daytime nap followed by a 6-h night time sleep opportunity, each before morning bright light. Eight of the 12 subjects obtained similar amounts of sleep in both conditions, and yet still showed significant reductions in phase advances with 6-h nights (1.7 versus 0.7 h, P

The dim light melatonin onset (DLMO) is the most reliable circadian phase marker in humans, but the cost of assaying samples is relatively high. Therefore, the authors examined differences between DLMOs calculated from hourly versus half-hourly sampling and differences between DLMOs calculated with two recommended thresholds (a fixed threshold of 3 pg/mL and a variable “3k” threshold equal to the mean plus two standard deviations of the first three low daytime points). The authors calculated these DLMOs from salivary dim light melatonin profiles collected from 122 individuals (64 women) at baseline. DLMOs derived from hourly sampling occurred on average only 6–8 min earlier than the DLMOs derived from half-hourly saliva sampling, and they were highly correlated with each other (r ≥ 0.89, p < .001). However, in up to 19% of cases the DLMO derived from hourly sampling was >30 min from the DLMO derived from half-hourly sampling. The 3 pg/mL threshold produced significantly less variable DLMOs than the 3k threshold. However, the 3k threshold was significantly lower than the 3 pg/mL threshold (p < .001). The DLMOs calculated with the 3k method were significantly earlier (by 22–24 min) than the DLMOs calculated with the 3 pg/mL threshold, regardless of sampling rate. These results suggest that in large research studies and clinical settings, the more affordable and practical option of hourly sampling is adequate for a reasonable estimate of circadian phase. Although the 3 pg/mL fixed threshold is less variable than the 3k threshold, it produces estimates of the DLMO that are further from the initial rise of melatonin.

Inflammatory bowel disease (IBD) is a waxing and waning disease characterized by diarrhea, abdominal pain and weight loss. Recently, there has been an increased interest in the roles that sleep, circadian rhythms and melatonin could have as regulators of inflammation in the Gl tract. Advances in our understanding of the molecular machinery of the circadian clock, and the discovery of clock genes in the GI tract are opening up new avenues of research for a role of sleep in IBD. Altering circadian rhythm significantly worsens the development of colitis in animal models, and preliminary human studies have shown that patients with IBD are at increased risk for altered sleep patterns. Further research is needed to clarify the role of disturbances in IBD.

Partial sleep deprivation is increasingly common in modern society. This study examined for the first time if partial sleep deprivation alters circadian phase shifts to bright light in humans. Thirteen young healthy subjects participated in a repeated-measures counterbalanced design with 2 conditions. Each condition had baseline sleep, a dim-light circadian phase assessment, a 3-day phase-advancing protocol with morning bright light, then another phase assessment. In one condition (no sleep deprivation), subjects had an 8-h sleep opportunity per night during the advancing protocol. In the other condition (partial sleep deprivation), subjects were kept awake for 4 h in near darkness (

Exogenous melatonin is increasingly used for its phase shifting and soporific effects. We generated a three pulse phase response curve (PRC) to exogenous melatonin (3 mg) by administering it to free-running subjects. Young healthy subjects (n = 27) participated in two 5 day laboratory sessions, each preceded by at least a week of habitual, but fixed sleep. Each 5 day laboratory session started and ended with a phase assessment to measure the circadian rhythm of endogenous melatonin in dim light using 30 min saliva samples. In between were three days in an ultradian dim light (< 150 lux)‐dark cycle (LD 2.5 : 1.5) during which each subject took one pill per day at the same clock time (3 mg melatonin or placebo, double blind, counterbalanced). Each individual’s phase shift to exogenous melatonin was corrected by subtracting their phase shift to placebo (a free-run). The resulting PRC has a phase advance portion peaking about 5 h before the dim light melatonin onset, in the afternoon. The phase delay portion peaks about 11 h after the dim light melatonin onset, shortly after the usual time of morning awakening. A dead zone of minimal phase shifts occurred around the first half of habitual sleep. The fitted maximum advance and delay shifts were 1.8 h and 1.3 h, respectively. This new PRC will aid in determining the optimal time to administer exogenous melatonin to achieve desired phase shifts and demonstrates that using exogenous melatonin as a sleep aid at night has minimal phase shifting effects.

Circadian (body clock) timing has a profound influence on mental health, physical health, and health behaviors. This review focuses on how light, melatonin, and other melatonin receptor agonist drugs can be used to shift circadian timing in patients with misaligned circadian rhythms. A brief overview of the human circadian system is provided, followed by a discussion of patient characteristics and safety considerations that can influence the treatment of choice. The important features of light treatment, light avoidance, exogenous melatonin, and other melatonin receptor agonists are reviewed, along with some of the practical aspects of light and melatonin treatment.

A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed.

Summary The dim light melatonin onset (DLMO) assists with the diagnosis and treatment of circadian rhythm sleep disorders. Home DLMOs are attractive for cost savings and convenience, but can be confounded by home lighting and sample timing errors. We developed a home saliva collection kit with objective measures of light exposure and sample timing. We report on our first test of the kit in a clinical population. Thirty-two participants with delayed sleep phase disorder (DSPD; 17 women, aged 18–52 years) participated in two back-to-back home and laboratory phase assessments. Most participants (66%) received at least one 30-s epoch of light >50 lux during the home phase assessments, but for only 1.5% of the time. Most participants (56%) collected every saliva sample within 5 min of the scheduled time. Eighty-three per cent of home DLMOs were not affected by light or sampling errors. The home DLMOs occurred, on average, 10.2 min before the laboratory DLMOs, and were correlated highly with the laboratory DLMOs (r = 0.93, P

Study objectives There is a need for the accurate assessment of circadian phase outside of the clinic/laboratory, particularly with the gold standard dim light melatonin onset (DLMO). We tested a novel kit designed to assist in saliva sampling at home for later determination of the DLMO. The home kit includes objective measures of compliance to the requirements for dim light and half-hourly saliva sampling. Design Participants were randomized to one of two 10-day protocols. Each protocol consisted of two back-to-back home and laboratory phase assessments in counterbalanced order, separated by a 5-day break. Setting Laboratory or participants' homes. Participants Thirty-five healthy adults, age 21-62 y. Interventions N/A. Measurements and results Most participants received at least one 30-sec epoch of light > 50 lux during the home phase assessments (average light intensity 4.5 lux), but on average for 50 lux or sampling errors. There was no significant difference between the home and laboratory DLMOs (P > 0.05); on average the home DLMOs occurred 9.6 min before the laboratory DLMOs. The home DLMOs were highly correlated with the laboratory DLMOs (r = 0.91, P Conclusions Participants were reasonably compliant to the home phase assessment procedures. The good agreement between the home and laboratory dim light melatonin onsets (DLMOs) demonstrates that including objective measures of light exposure and sample timing during home saliva sampling can lead to accurate home DLMOs. Clinical trial registration Circadian Phase Assessments at Home, http://clinicaltrials.gov/show/NCT01487252, NCT01487252.

Both light and melatonin can be used to phase shift the human circadian clock, but the phase-advancing effect of the combination has not been extensively investigated.The objective of the study was to determine whether phase advances induced by morning intermittent bright light and a gradually advancing sleep schedule could be increased with afternoon melatonin.Healthy adults (25 males, 19 females, between the ages of 19 and 45 yr) participated in the study.There were 3 d of a gradually advancing sleep/dark period (wake time 1 h earlier each morning), bright light on awakening [four 30-min bright-light pulses (approximately 5000 lux) alternating with 30 min room light60 lux] and afternoon melatonin, either 0.5 or 3.0 mg melatonin timed to induce maximal phase advances, or matching placebo. The dim light melatonin onset was measured before and after the treatment to determine the phase advance.There were significantly larger phase advances with 0.5 mg (2.5 h, n = 16) and 3.0 mg melatonin (2.6 h, n = 13), compared with placebo (1.7 h, n = 15), but there was no difference between the two melatonin doses. Subjects did not experience jet lag-type symptoms during the 3-d treatmentAfternoon melatonin, morning intermittent bright light, and a gradually advancing sleep schedule advanced circadian rhythms almost 1 h/d and thus produced very little circadian misalignment. This treatment could be used in any situation in which people need to phase advance their circadian clock, such as before eastward jet travel or for delayed sleep phase syndrome.

The time at which the dim light melatonin onset (DLMO) occurs can be used to ensure the correct timing of light and/or melatonin administration in order to produce desired circadian phase shifts. Sometimes however, measuring the DLMO is not feasible. Here we determined if the DLMO was best estimated from fixed sleep times (based on habitual sleep times) or free (ad libitum) sleep times. Young healthy sleepers on fixed (n = 60) or free (n = 60) sleep schedules slept at home for 6 days. Sleep times were recorded with sleep logs verified with wrist actigraphy. Half-hourly saliva samples were then collected during a dim light phase assessment and were later assayed to determine the DLMO. We found that the DLMO was more highly correlated with sleep times in the free sleepers than in the fixed sleepers (DLMO versus wake time, r = 0.70 and r = 0.44, both P < 0.05). The regression equation between wake time and the DLMO in the free sleepers predicted the DLMO in an independent sample of free sleepers (n = 23) to within 1.5 h of the actual DLMO in 96% of cases. These results indicate that the DLMO can be readily estimated in people whose sleep times are minimally affected by work, class and family commitments. Further work is necessary to determine if the DLMO can be accurately estimated in people with greater work and family responsibilities that affect their sleep times, perhaps by using weekend wake times, and if this method will apply to the elderly and patients with circadian rhythm disorders.

Small shifts in circadian timing occur frequently as a result of daylight saving time or later weekend sleep. These subtle shifts in circadian phase have been shown to influence subjective sleepiness, but it remains unclear if they can significantly affect performance. In a retrospective analysis we examined performance on the Psychomotor Vigilance Test before bedtime and after wake time in 11 healthy adults on fixed sleep schedules based on their habitual sleep times. The dim light melatonin onset, a marker of circadian timing, was measured on two occasions. An average 1.1 hour shift away from a proposed optimal circadian phase angle (6 hours between melatonin onset and midpoint of sleep) significantly slowed mean, median and fastest 10% reaction times before bedtime and after wake time (p

Bright light is the recommended treatment for winter seasonal affective disorder (SAD). Previously we showed that the antidepressant effect of morning (but not evening) light was greater than placebo after 3 weeks of treatment. Here, we determined if the magnitude and direction of circadian rhythm phase shifts produced by the bright light in the previous study were related to the antidepressant effects. Twenty-six SAD patients from the original sample of 96 had their rectal temperature continuously monitored while they participated in a placebo-controlled parallel design conducted over six winters. After a baseline week, there were three treatments for 4 weeks-morning light, evening light, or morning placebo. Bright light was produced by light boxes (approximately 6000 lux). Placebos were sham negative ion generators. All treatments were 1.5 h in duration. Depression ratings were made weekly by blind raters. Circadian phase shifts were determined from changes in the timing of the core body temperature minimum (Tmin). Morning light advanced and evening light delayed the Tmin by about 1 h. The placebo treatment did not alter circadian phase. As the sleep schedule was held constant, morning light increased and evening light decreased the Tmin to wake interval, or phase angle between circadian rhythms and sleep. Phase advance shifts and increases in the phase angle were only weakly associated with antidepressant response. However, there was an inverted U-shaped function showing that regardless of treatment assignment the greatest antidepressant effects occurred when the phase angle was about 3h, and that patients who moved closer to this phase angle benefited more than those who moved farther from it. However 46% of our sample had a phase angle within 30 min of this 3 h interval at baseline. So it does not appear that an abnormal phase angle can entirely account for the etiology of SAD. A majority (75%) of the responders by strict joint criteria had a phase angle within this range after treatment, so it appears that obtaining the ideal phase relationship may account for some, but not all of the antidepressant response. In any case, regardless of the mechanism for the antidepressant effect of morning light, it can be enhanced when patients sleep at the ideal circadian phase and reduced when they sleep at a more abnormal circadian phase.

The aim of this study was to undertake a preliminary investigation of the novel hypothesis that weakened circadian rhythmicity is an aspect of the psychobiology of neuroticism (N). Two groups of subjects [young healthy females categorised as High N (N=8) or Low N (N=6)] were compared in terms of a classical circadian variable (the unmasked rhythm in core body temperature), and a validated psychological variable (diurnal rhythm in Positive Affect), under two experimental protocols (constant routine and ambulatory). As predicted, model-fitting analyses found that the High N group was characterised by attenuated circadian amplitudes in unmasked body temperature under both protocols. Also as hypothesised Positive Affect exhibited a circadian rhythm that was only significant in the Low N group. A stronger synchronisation between the biological and psychological rhythms was also observed in the Low N group. Results are discussed in terms of the implications of a possible circadian diathesis for disorders and complaints across the neurotic spectrum.