Search Results (18)

Circadian rhythms are intrinsic, with roughly 24 h oscillations that coordinate many physiological functions and are increasingly recognized as key determinants of human health. When these rhythms become misaligned, there is an increased risk for neurodegenerative and psychiatric disorders, metabolic syndrome, sleep disturbances, and even certain cancers. The hormones, melatonin that rises in the evening and cortisol that peaks shortly after awakening, represent crucial biochemical markers of the circadian phase. This review systematically evaluates contemporary techniques for quantifying melatonin and cortisol, comparing biological matrices (blood, saliva, urine) alongside analytical platforms. Special focus is placed on two clinically informative markers: Dim Light Melatonin Onset (DLMO) and the Cortisol Awakening Response (CAR). We compared immunoassays with liquid chromatography tandem mass spectrometry (LC MS/MS), highlighting differences in sensitivity, specificity, and laboratory feasibility. Potential confounders, including ambient light, body posture, and exact sampling times—are discussed in detail, to show the capacity of providing the most reliable results. By emphasizing the need for standardized protocols and controlled sampling conditions, this review provides essential guidance for researchers and clinicians aiming to assess the circadian biomarkers melatonin and cortisol with precision since they can be used in clinical practice as diagnostic and prognostic tools for assessing numerous pathologies. Full article

Modern elite football is becoming increasingly physically demanding, often requiring training and matches to be played at night. This schedule may disrupt circadian rhythms and melatonin secretion, thereby impairing sleep and recovery. This study investigated the effects of training time on melatonin secretion, circadian phase markers, and sleep parameters in elite youth soccer players. Forty male players (aged 16–18 years) from an elite Spanish youth football club were studied. Two groups followed the same training program but trained either in the morning (MT) or in the evening (ET). Salivary melatonin was measured at six time points to determine the mean levels, dim light melatonin onset (DLMO), amplitude, and acrophase. Chronotype, sleep quality (PSQI), and daytime sleepiness (ESS) were assessed using validated questionnaires. Dietary intake and anthropometric variables were also recorded. The MT group had higher mean melatonin levels (p = 0.026) and earlier DLMO (p = 0.023) compared to the ET group. Sleep quality was significantly better in the MT group (p < 0.001), despite shorter sleep duration (p = 0.014). No major differences in diet or anthropometry were observed. The chronotype had a secondary effect on the circadian markers. Evening training is associated with alterations in melatonin rhythms and reduced sleep quality, possibly due to light-induced chronodisruption. These findings highlight the importance of training timing as a modifiable factor in the chronobiology and recovery of athletes. Incorporating circadian principles into training schedules may optimize resting time and thus performance and long-term health in athletes. Full article

Despite extensive research on the effects of sleep restriction on adolescent health, the field lacks experimental methods to study the health effects of mistimed sleep, which is also common among adolescents. This paper describes a novel 3-week experimental protocol that was designed to compare sleep restriction, like what many adolescents experience on school nights, against sleep that meets the recommended duration but is timed to be relatively aligned or misaligned with their circadian phase. Healthy 14–18-year-olds, classified as early (“Lark”) and late (“Owl”) chronotypes, entered a six-night chronotype-aligned stabilization condition, followed by five nights of sleep restriction, a return to the stabilization schedule, and five nights of healthy sleep duration (HS). During HS, participants were randomly assigned to early-to-bed versus late-to-rise arms, intended to align with or misalign with their circadian phase. Actigraphy monitored sleep, and weekly dim-light melatonin onset (DLMO) assessed circadian phase. Analyses confirmed that the protocol met five key validation metrics related to differential attrition, sleep timing, circadian phase, and experimental induction of HS that is timed to be relatively aligned vs. misaligned with circadian phase. This protocol appears useful for future research into how misaligned sleep patterns, which occur regularly for many adolescents, may impact health. Full article

The static lighting condition (SLC) in confined spaces may pose great challenges to the health of long-stay workers, inducing sleep disorders, cognitive decline, and negative emotions such as depression or anxiety. To explore human responses to the SLC (300 lx and 6000 K), 20 young subjects (22.6 ± 1.88 years old) were recruited in the underground confined lab for a week by measuring melatonin, core body temperature (CBT), subjective alertness (KSS score), sleep quality (Pittsburgh Sleep Quality Index, PSQI), Psychomotor Vigilance Task (PVT), Hamilton Depression Scale (HAMD) and Self-rating Anxiety Scale (SAS). The results showed a posterior shift in circadian rhythm after 1 week of confinement, with 0.62 h delay of dim light melatonin onset (DLMO), higher melatonin concentrations in the evening, lower melatonin concentrations at midnight, a day-by-day increase in KSS and CBT at bedtime, but this decreased daily when waking up, with cumulative effects. There was a progressive increase in sleep latency, PSQI scores, response time and scores of subjective emotion scales, meaning worse sleep, performance and emotional state. Due to limited exposure to high-lighting stimuli during the daytime, the initial concentrations of melatonin increased in the evening and decreased before sleep. In confined spaces, active health interventions by dynamic lighting patterns were proposed to safeguard human health and performance. Full article

Dim light melatonin onset (DLMO) is considered the most reliable marker of the circadian rhythm phase in humans. DLMO may moderately correlate with sleep onset and sleep offset time. There are no sufficient data about the correlations between DLMO and clinical scales assessing sleep quality and daytime symptoms of poor night sleep. The aim of the study was to determine the association between DLMO and basic sleep parameters from actigraphy and sleep diaries, as well as the association between DLMO and the following insomnia clinical scales: the Athens Insomnia Scale (AIS), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and chronotype questionnaires: Morningness–Eveningness Questionnaire (MEQ) and Composite Scale of Morningness (CSM). Participants of the study were healthy volunteers. Sleep parameters were measured by sleep diaries and actigraphy, and the following clinical scales: the AIS, ISI, and ESS, and chronotype questionnaires: MEQ and CSM. DLMO was calculated based on plasma melatonin concentration. The blood samples were collected hourly at five time points between 20:00 and 00:00 during the session in dim red light (<50 lux). Melatonin concertation was determined by LC-MS/MS. Twenty-one volunteers participated in the study. DLMO was calculated in 12 participants. There was a significant correlation between DLMO and ISI (r = 0.60, p = 0.038) and ESS (r = 0.61, p = 0.034). The correlation coefficient between the DLMO and the AIS was also high, however insignificant (r = 0.57, p = 0.054). There were no significant correlations between DLMO and chronotype scales MEQ and CSM. DLMO did not correlate with sleep onset and sleep offset; however, DLMO correlated with the Sleep Fragmentation Index (SFI) (r = 0.67, p = 0.017). DLMO is associated with poorer sleep maintenance, a stronger feeling of insomnia, and sleepiness during the day. Simultaneously, chronotype pattern and circadian rhythm parameters do not correlate with DLMO. Biological circadian rhythm does not reflect the real-life sleep–wake rhythm, indicating that the lifestyle is more often disconnected from the biological clock. Full article

Humans have a circadian rhythm for which the period varies among individuals. In the present study, we investigated the amount of natural phase delay of circadian rhythms after spending a day under dim light (Day 1 to Day 2) and the amount of phase advance due to light exposure (8000 lx, 4100 K) the following morning (Day 2 to Day 3). The relationships of the phase shifts with the circadian phase, chronotype and sleep habits were also investigated. Dim light melatonin onset (DLMO) was investigated as a circadian phase marker on each day. In the 27 individuals used for the analysis, DLMO was delayed significantly (−0.24 ± 0.33 h, p < 0.01) from Day 1 to Day 2 and DLMO was advanced significantly (0.18 ± 0.36 h, p < 0.05) from Day 2 to Day 3. There was a significant correlation between phase shifts, with subjects who had a greater phase delay in the dim environment having a greater phase advance by light exposure (r = −0.43, p < 0.05). However, no significant correlations with circadian phase, chronotype or sleep habits were found. These phase shifts may reflect the stability of the phase, but do not account for an individual’s chronotype-related indicators. Full article

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. Full article

Insomnia is a highly prevalent sleep disorder with strong bidirectional associations with depressive symptoms. The circadian preference for eveningness has been shown to be associated with depressive symptoms in insomnia and other mental health conditions. However, there is a lack of studies in insomnia investigating whether objective measures, such as dim light melatonin onset (DLMO) or polysomnographic (PSG) sleep, are associated with depressive symptoms. Therefore, we investigated the associations between subjective measures (questionnaires assessing anxiety, sleep quality and circadian preference, and sleep diary) and depressive symptoms and whether the addition of objective measures (DLMO, PSG parameters) would strengthen the associations with depressive symptoms. In 115 insomnia disorder patients we found that anxiety was strongly associated with depressive symptoms in a model including circadian preference, dysfunctional beliefs of sleep, and self-reported previous depressive symptoms (R² = 0.496, p < 0.001). The addition of sleep diary measures did not strengthen the model. We also found that the addition of objective measures (DLMO, PSG parameters) did not improve the subjective associations with depressive symptoms. Our data suggest that objective circadian markers are less important in the prediction of depressive symptoms in insomnia compared to subjective measures. Full article

In humans, physiological outputs of the body’s internal clock (i.e., saliva, serum, and temperature) can be collected to quantify the timing of the circadian system. In-lab assessment of salivary melatonin in a dimly lit environment is a common approach for adolescents and adults; however, the reliable measurement of melatonin onset in toddlers and preschoolers requires a modification of laboratory methods. For > 15 years, we have successfully collected data from ~250 in-home dim light melatonin onset (DLMO) assessments of children aged 2–5 years. Although in-home studies of circadian physiology may introduce a host of challenges and may increase the risk of incomplete data (e.g., accidental light exposure), in-home studies afford more comfort (e.g., less arousal in children) and flexibility for families. Here, we provide effective tools and strategies to assess children’s DLMO, a reliable marker of circadian timing, through a rigorous in-home protocol. We first describe our basic approach, including the study protocol, collection of actigraphy data, and strategies for training child participants to complete procedures. Next, we detail how to convert the home into a “cave”, or dim-light environment, and present guidelines for timing the salivary data collection. Lastly, we provide helpful tips to increase participants’ compliance based upon behavioral and developmental science tenets. Full article

Night shift workers experience circadian misalignment and sleep disruption, which impact hunger and food consumption. The study aim was to assess the impact of chronotype on hunger and snack consumption during a night shift with acute sleep deprivation. Seventy-two (36f, 36m) healthy adults participated in a laboratory study. A sleep opportunity (03:00–12:00) was followed by a wake period (12:00–23:00) and a simulated night shift (23:00–07:00). Subjective measures of hunger, prospective consumption, desire to eat fruit, and desire to eat fast food were collected before (12:20, 21:50) and after (07:20) the night shift. Snack opportunities were provided before (15:10, 19:40) and during (23:50, 03:30) the night shift. A tertile split of the dim light melatonin onset (DLMO) distribution defined early (20:24 ± 0:42 h), intermediate (21:31 ± 0:12 h), and late chronotype (22:56 ± 0:54 h) categories. There were no main effects of chronotype on any subjective measure (p = 0.172–0.975), or on snack consumption (p = 0.420), and no interactions between chronotype and time of day on any subjective measure (p = 0.325–0.927) or on snack consumption (p = 0.511). Differences in circadian timing between chronotype categories were not associated with corresponding differences in hunger, prospective consumption, desire to eat fruit, desire to eat fast food, or snack consumption at any measurement timepoint. Full article

The study’s aim was to examine the effect of chronotype on cognitive performance during a single night shift. Data were collected from 72 (36f) young, healthy adults in a laboratory study. Participants had a 9 h sleep period (03:00–12:00) followed by an 8 h night shift (23:00–07:00). During the night shift, participants completed five test sessions, which included measures of subjective sleepiness, subjective alertness, and sustained attention (i.e., psychomotor vigilance task; PVT). Dim light melatonin onset (DLMO) was derived from saliva samples taken during the evening preceding the night shift. A tertile split of DLMO was used to determine three chronotype categories: earlier (DLMO = 20:22 ± 0:42), intermediate (DLMO = 21:31 ± 0:13), and later (DLMO = 22:54 ± 0:54). There were (a) significant main effects of test session (all p < 0.001); (b) no main effects of chronotype; and (c) no interaction effects between chronotype and test session on sleepiness, alertness, PVT response time, and PVT lapses. The results indicate that under controlled sleeping conditions, chronotype based on dim light melatonin onset did not affect nighttime performance. Differences in performance during night shift between chronotypes reported by field studies may be related to differences in the amount and/or timing of sleep before or between night shifts, rather than circadian timing. Full article

Chronotype reflects circadian timing and can be determined from biological markers (e.g., dim light melatonin onset; DLMO), or questionnaires (e.g., Morningness-Eveningness Questionnaire; MEQ, or Munich Chronotype Questionnaire; MCTQ). The study’s aim was to quantify concordance between chronotype categorisations based on these measures. A total of 72 (36f) young, healthy adults completed the MEQ and MCTQ and provided saliva samples hourly in dim light during the evening in a laboratory. The corrected midpoint of sleep on free days (MSF_sc) was derived from MCTQ, and tertile splits were used to define early, intermediate and late DLMO-CT, MEQ-CT and MSF_sc-CT chronotype categories. DLMO correlated with MEQ score (r = −0.25, p = 0.035) and MSF_sc (r = 0.32, p = 0.015). For early, intermediate and late DLMO-CT categories, mean(SD) DLMO were 20:25(0:46), 21:33(0:10) and 23:03(0:53). For early, intermediate and late MEQ-CT categories, mean(SD) MEQ scores were 60.5(5.3), 51.4(2.9) and 40.8 (5.0). For early, intermediate and late MSF_sc-CT categories, mean(SD) MSF_sc were 03:23(0:34), 04:37(0:12) and 05:55(0:48). Low concordance of categorisations between DLMO-CT and MEQ-CT (37%), and between DLMO-CT and MSF_sc-CT (37%), suggests chronotype categorisations depend on the measure used. To enable valid comparisons with previous results and reduce the likelihood of misleading conclusions, researchers should select measures and statistical techniques appropriate to the construct of interest and research question. Full article

Melatonin has been used preclinically and clinically for different purposes. Some applications are related to readjustment of circadian oscillators, others use doses that exceed the saturation of melatonin receptors MT₁ and MT₂ and are unsuitable for chronobiological purposes. Conditions are outlined for appropriately applying melatonin as a chronobiotic or for protective actions at elevated levels. Circadian readjustments require doses in the lower mg range, according to receptor affinities. However, this needs consideration of the phase response curve, which contains a silent zone, a delay part, a transition point and an advance part. Notably, the dim light melatonin onset (DLMO) is found in the silent zone. In this specific phase, melatonin can induce sleep onset, but does not shift the circadian master clock. Although sleep onset is also under circadian control, sleep and circadian susceptibility are dissociated at this point. Other limits of soporific effects concern dose, duration of action and poor individual responses. The use of high melatonin doses, up to several hundred mg, for purposes of antioxidative and anti-inflammatory protection, especially in sepsis and viral diseases, have to be seen in the context of melatonin’s tissue levels, its formation in mitochondria, and detoxification of free radicals. Full article

Breakfast is often described as “the most important meal of the day” and human studies have revealed that post-prandial responses are dependent on meal timing, but little is known of the effects of meal timing per se on human circadian rhythms. We evaluated the effects of skipping breakfast for 6 days on core body temperature, dim light melatonin onset, heart rate variability, and clock gene expression in 10 healthy young men, with a repeated-measures design. Subjects were provided an isocaloric diet three times daily (3M) or two times daily (2M, i.e., breakfast skipping condition) over 6 days. Compared with the 3M condition, the diurnal rhythm of the core body temperature in the 2M condition was delayed by 42.0 ± 16.2 min (p = 0.038). On the other hand, dim light melatonin onset, heart rate variability, and clock gene expression were not affected in the 2M condition. Skipping breakfast for 6 days caused a phase delay in the core body temperature in healthy young men, even though the sleep–wake cycle remained unchanged. Chronic effects of skipping breakfast on circadian rhythms remain to be studied. Full article

The dichotomy index (I < O), a quantitative estimate of the circadian regulation of daytime activity and sleep, predicted overall cancer survival and emergency hospitalization, supporting its integration in a mHealth platform. Modifiable causes of I < O deterioration below 97.5%—(I < O)_low—were sought in 25 gastrointestinal cancer patients and 33 age- and sex-stratified controls. Rest-activity and temperature were tele-monitored with a wireless chest sensor, while daily activities, meals, and sleep were self-reported for one week. Salivary cortisol rhythm and dim light melatonin onset (DLMO) were determined. Circadian parameters were estimated using Hidden Markov modelling, and spectral analysis. Actionable predictors of (I < O)_low were identified through correlation and regression analyses. Median compliance with protocol exceeded 95%. Circadian disruption—(I < O)_low—was identified in 13 (52%) patients and four (12%) controls (p = 0.002). Cancer patients with (I < O)_low had lower median activity counts, worse fragmented sleep, and an abnormal or no circadian temperature rhythm compared to patients with I < O exceeding 97.5%—(I < O)_high—(p < 0.012). Six (I < O)_low patients had newly-diagnosed sleep conditions. Altered circadian coordination of rest-activity and chest surface temperature, physical inactivity, and irregular sleep were identified as modifiable determinants of (I < O)_low. Circadian rhythm and sleep tele-monitoring results support the design of specific interventions to improve outcomes within a patient-centered systems approach to health care. Full article