Nocturnal Melatonin Secretion Research Articles

Effects of evening smartphone use on sleep and declarative memory consolidation in male adolescents and young adults

Abstract Exposure to short-wavelength light before bedtime is known to disrupt nocturnal melatonin secretion and can impair subsequent sleep. However, while it has been demonstrated that older adults are less affected by short-wavelength light, there is limited research exploring differences between adolescents and young adults. Furthermore, it remains unclear whether the effects of evening short-wavelength light on sleep architecture extend to sleep-related processes, such as declarative memory consolidation. Here, we recorded polysomnography from 33 male adolescents (15.42 ± 0.97 years) and 35 male young adults (21.51 ± 2.06 years) in a within-subjects design during three different nights to investigate the impact of reading for 90min either on a smartphone with or without a blue-light filter or from a printed book. We measured subjective sleepiness, melatonin secretion, sleep physiology, and sleep-dependent memory consolidation. While subjective sleepiness remained unaffected, we observed a significant melatonin-attenuation effect in both age groups immediately after reading on the smartphone without a blue-light filter. Interestingly, adolescents fully recovered from the melatonin attenuation in the following 50min before bedtime, whereas adults still, at bedtime, exhibited significantly reduced melatonin levels. Sleep-dependent memory consolidation and the coupling between sleep spindles and slow oscillations were not affected by short-wavelength light in both age groups. Nevertheless, adults showed a reduction in N3 sleep during the first night-quarter. In summary, avoiding smartphone use in the last hour before bedtime is advisable for adolescents and young adults to prevent sleep disturbances. Our research empirically supports general sleep hygiene advice and can inform future recommendations regarding the use of smartphones and other screen-based devices before bedtime.

Power Analysis for Human Melatonin Suppression Experiments.

In humans, the nocturnal secretion of melatonin by the pineal gland is suppressed by ocular exposure to light. In the laboratory, melatonin suppression is a biomarker for this neuroendocrine pathway. Recent work has found that individuals differ substantially in their melatonin-suppressive response to light, with the most sensitive individuals being up to 60 times more sensitive than the least sensitive individuals. Planning experiments with melatonin suppression as an outcome needs to incorporate these individual differences, particularly in common resource-limited scenarios where running within-subjects studies at multiple light levels is costly and resource-intensive and may not be feasible with respect to participant compliance. Here, we present a novel framework for virtual laboratory melatonin suppression experiments, incorporating a Bayesian statistical model. We provide a Shiny web app for power analyses that allows users to modify various experimental parameters (sample size, individual-level heterogeneity, statistical significance threshold, light levels), and simulate a systematic shift in sensitivity (e.g., due to a pharmacological or other intervention). Our framework helps experimenters to design compelling and robust studies, offering novel insights into the underlying biological variability in melatonin suppression relevant for practical applications.

Two oscillatory components detected by forced splitting of the sleep-wake cycle in humans.

The sleep-wake cycle of human subjects was artificially split into two episodes by imposing an 8-h light and 4-h dark cycle (LD 8:4) twice a day for 7 days, which was followed by a 3-day free-running session. Sleep was permitted only in the dark period. The subjects in the ordinary group were exposed to ordinary light (ca. 500 lx) in the 8-h light period, and those in the bright light group to bright (ca. 5,000 lx) and ordinary light alternatively with bright light after the first dark period (2400-400). Split sleeps persisted in the free-running session with the major episode around the first dark period and the minor episode around the second dark period. By contrast, circadian melatonin rhythm in the free-running session significantly phase delayed in the ordinary light group, but phase advanced in the bright light group, keeping the melatonin rhythm unsplit. The length of nocturnal melatonin secretion (NMS) was significantly shortened in the bright light group. Interestingly, the falling phase of NMS advanced significantly further than the rising phase. Such a difference was not detected in the ordinary light group. Similar differences were observed in the body temperature rhythm. These findings indicated oscillatory mechanisms underlying split sleeps distinct from the circadian pacemaker and suggested an involvement of different circadian oscillators in the rising and falling phases of NMS, which is consistent with the dual oscillator model proposed for the circadian system of nocturnal rodents.NEW & NOTEWORTHY The present study demonstrated that human sleep was separated into two essentially identical components, which persisted under constant conditions, suggesting circadian oscillator underlying split-sleep episodes. The study also indicated differential light sensitivities in the rising and falling phases of circadian melatonin rhythm, indicating the involvement of two different oscillators. These results consisted of the evening and morning dual-oscillator hypothesis for the circadian pacemaker and the hierarchical model for the pacemaker and sleep-wake cycle.

Differential responses to artificial photoperiods of the rising and falling phases of human melatonin rhythm are consistent with a dual oscillator hypothesis.

Circadian rhythms and sleep-wake cycles were measured in volunteers staying singly in temporal isolation unit where they were exposed to artificial short and long light-dark (LD) cycles for 7 days. The long day consisted of 16-h light and 8-h dark (LD 16:8) and the short day consisted of 8-h light and 16-h dark (LD 8:16). During the light period, bright light of approximately 5,000 lux was given from the ceiling and during the dark period there was no illumination. Sleep was monitored by bed sensors, wrist actiwatch, and polysomnography (PSG) on the first and last nights of the schedule. Sleep length was significantly longer under LD 8:16 than under LD 16:8 and the sleep quality estimated by PSG was worse under LD 8:16 than under LD 16:8, which were comparable to natural seasonality in sleep. The circadian rhythm in plasma melatonin was measured in dim light (10 lux) before and after the LD exposures. The nocturnal melatonin secretion (NMS) was significantly longer after LD 8:16 than after LD 16:8 due to differential phase shifts of the rising and falling phases of NMS. After LD 8:16, the falling phase was much advanced than the rising phase, whereas after LD 16:8 the rising phase was much delayed than the falling phase, resulting in the NMS compression. These results indicate that the light sensitivity in terms of phase shifting is different in the two circadian phases, supporting a dual oscillator hypothesis with different phase-response curves for light in the human circadian system.NEW & NOTEWORTHY The present study demonstrated differential light responsiveness of the rising and falling phases of nocturnal melatonin secretion in human subjects exposed to artificial long (LD 16:8) and short days (LD 8:16) and suggested the involvement of different oscillators under these phases. The findings well mimicked the seasonality of the circadian rhythms in nature and consisted with the evening/morning dual oscillator hypothesis proposed originally for nocturnal rodents, providing a new concept for the human circadian system.

The spectral sensitivity of human circadian phase resetting and melatonin suppression to light changes dynamically with light duration

Human circadian, neuroendocrine, and neurobehavioral responses to light are mediated primarily by melanopsin-containing intrinsically-photosensitive retinal ganglion cells (ipRGCs) but they also receive input from visual photoreceptors. Relative photoreceptor contributions are irradiance- and duration-dependent but results for long-duration light exposures are limited. We constructed irradiance-response curves and action spectra for melatonin suppression and circadian resetting responses in participants exposed to 6.5-h monochromatic 420, 460, 480, 507, 555, or 620 nm light exposures initiated near the onset of nocturnal melatonin secretion. Melatonin suppression and phase resetting action spectra were best fit by a single-opsin template with lambdamax at 481 and 483 nm, respectively. Linear combinations of melanopsin (ipRGC), short-wavelength (S) cone, and combined long- and medium-wavelength (L+M) cone functions were also fit and compared. For melatonin suppression, lambdamax was 441 nm in the first quarter of the 6.5-h exposure with a second peak at 550 nm, suggesting strong initial S and L+M cone contribution. This contribution decayed over time; lambdamax was 485 nm in the final quarter of light exposure, consistent with a predominant melanopsin contribution. Similarly, for circadian resetting, lambdamax ranged from 445 nm (all three functions) to 487 nm (L+M-cone and melanopsin functions only), suggesting significant S-cone contribution, consistent with recent model findings that the first few minutes of a light exposure drive the majority of the phase resetting response. These findings suggest a possible initial strong cone contribution in driving melatonin suppression and phase resetting, followed by a dominant melanopsin contribution over longer duration light exposures.

Fluoxetine modifies circadian rhythm by reducing melatonin content in zebrafish

Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI), increases the serotonin levels in the brain to treat depression. Antidepressants have been demonstrated to modulate circadian rhythm, but the underlying mechanisms by which antidepressants regulate circadian rhythm require more research. This study aimed to investigate the role of FLX on circadian rhythm by analyzing the movement behavior and internal circadian oscillations in zebrafish. The results showed that the expression of clock genes clock1a and bmal1b was significantly down-regulated, and the amplitude reduction and phase shift were observed after FLX treatment. Furthermore, FLX exposure inhibited the expression of aanat2, which led to a decrease in nocturnal melatonin secretion. aanat2-/- larvae showed disrupted circadian rhythm. These findings may help reveal the effect of FLX exposure on the circadian rhythm and locomotor activity. It may provide theoretical data for the clinical application of FLX.

Melatonin in razor clam Sinonovacula constricta: Examination of metabolic pathways, tissue distribution, and daily rhythms

Melatonin affects physiological processes that have circadian and seasonal cycles and causes behavioural changes in nearly all organisms, ranging from bacteria to mammals. However, no studies have focused on the presence, biosynthetic pathway, and rhythms of melatonin in bivalves, which are considered as the class of molluscs with the highest economic value. Here, the metabolic pathway and tissue distribution of melatonin, tissue transcription profiles of melatonin-related genes [key synthases arylalkylamine N-acetyltransferase type 2 and 5 (aanat2, aanat5), N-acetylserotonin methyltransferase (asmt), and melatonin receptor type 1 A1 and C3 (MTNR1A1, MTNR1C3)], daily changes in melatonin, transcripts of genes, and effects of four lights (blue, cyan, orange, and red) during the night on melatonin secretion were studied in a bivalve species, razor clam Sinonovacula constricta. Our results showed the presence of complete metabolic and circadian entrainment pathways of melatonin. The melatonin content in the lymphocytes and labial palp was higher than that in the other studied tissues, and aanat2, aanat5, asmt, MTNR1A1, and MTNR1C3 mRNA levels were the highest in the labial palp. Melatonin fluctuated rhythmically in lymphocytes and labial palps and increased at night. Similarly, aanat2, aanat5, asmt, MTNR1A1, and MTNR1C3 mRNA levels were rhythmic in the labial palp, peaking at night. In addition, blue light effectively inhibited the nocturnal secretion of melatonin in the clam. In summary, our results suggest that melatonin plays a role in light signal transduction and the circadian system in S. constricta.

Night melatonin levels affect cognition in diurnal animals: Molecular insights from a corvid exposed to an illuminated night environment

This study investigated the role of nocturnal melatonin secretion in the cognitive performance of diurnal animals. An initial experiment measured the cognitive performance in Indian house crows treated for 11 days with 12 h light at 1.426 W/m2 (∼150 lux) coupled with 12 h of 0.058 W/m2 (∼6-lux) dim light at night (dLAN) or with absolute darkness (0 lux dark night, LD). dLAN treatment significantly decreased midnight melatonin levels and negatively impacted cognitive performance. Subsequently, the role of exogenous melatonin (50 μg; administered intraperitoneally half an hour before the night began) was assessed on the regulation of cognitive performance in two separate experimental cohorts of crows kept under dLAN; LD controls received vehicle. Exogenous melatonin restored its mid-night levels under dLAN at par with those under LD controls, and improved the cognitive performance, as measured in the innovative problem-solving, and spatial and pattern learning-memory efficiency tests in dLAN-treated crows. There were concurrent molecular changes in the cognition-associated brain areas, namely the hippocampus, nidopallium caudolaterale and midbrain. In particular, the expression levels of genes involved in neurogenesis and synaptic plasticity (bdnf, dcx, egr1, creb), and dopamine synthesis and signalling (th, drd1, drd2, darpp32, taar1) were restored to LD control levels in crows treated with illuminated nights and received melatonin. These results demonstrate that the maintenance of nocturnal melatonin levels is crucial for an optimal higher-order brain function in diurnal animals in the face of an environmental threat, such as light pollution.

Effect of night-shift work on cortisol circadian rhythm and melatonin levels.

ObjectivesNight-shift work has been associated with several negative effects on worker’s health, possibly due to circadian desynchronization, sleep deprivation and suppression of nocturnal melatonin secretion including exposure to light during the work shift. The objective of this study was to evaluate the impact of fixed night-shift work versus day-shift work on the sleep-wake cycle and on the night and day levels of cortisol and melatonin.Material and MethodsSaliva samples were obtained from 36 individuals, 19 day workers (12 women and 7 men) and 17 night workers (12 women and 5 men) from a university hospital in southern Brazil, with no history of chronic diseases. Demographic and personal information were obtained through a self-administered questionnaire and sleep information by the Munich chronotype questionnaire.ResultsSalivary cortisol showed normal circadian rhythm in day- and night-shift workers, but was attenuated in night-shift workers during their working hours and on leave days. Night workers sleep fewer hours at night and have higher negative social jet lag than day workers.ConclusionIntervals between night shifts can be beneficial for the recovery of the hypothalamic-pituitary-adrenal axis, minimizing the negative effects on workers’ health, in addition to a preventive approach to aspects related to sleep hygiene and healthy life habits.

Interactions between nocturnal melatonin secretion, metabolism, and sleeping behavior in adolescents with obesity

Background/objectivesSleeping behavior and individual prospensity in sleep timing during a 24 h period, known as chronotypes, are underestimated factors, which may favor the development of obesity and metabolic diseases. Furthermore, melatonin is known to play an important role in circadian rhythm, but was also suggested to directly influence metabolism and bodyweight regulation. Since disturbed and shifted sleep rhythms have been observed in adolescents with obesity, this study aimed to investigate potential interactions between melatonin secretion, chronobiology, and metabolism. In addition, the influence of artificial light especially emitted by electronic devices on these parameters was of further interest.Subjects/methodsWe performed a cross-sectional study including 149 adolescents (mean age 14.7 ± 2.1 years) with obesity. Metabolic blood parameters (e.g., cholesterol, triglycerides, uric acid, and insulin) were obtained from patients and correlated with nocturnal melatonin secretion. Melatonin secretion was determined by measuring 6-sulfatoxymelatonin (MT6s), the major metabolite of melatonin in the first-morning urine, and normalized to urinary creatinine levels to account for the urinary concentration. Chronobiologic parameters were further assessed using the Munich ChronoType Questionnaire.ResultsSubjects with insulin resistance (n = 101) showed significantly lower nocturnal melatonin levels compared to those with unimpaired insulin secretion (p = 0.006). Furthermore, triglyceride (p = 0.012) and elevated uric acid levels (p = 0.029) showed significant associations with melatonin secretion. Patients with late chronotype showed a higher incidence of insulin resistance (p = 0.018). Moreover, late chronotype and social jetlag were associated with the time and duration of media consumption.ConclusionWe identified an association of impaired energy metabolism and lower nocturnal melatonin secretion in addition to late chronotype and increased social jetlag (misalignment of biological and social clocks) in adolescents with obesity. This might point towards a crucial role of chronotype and melatonin secretion as risk factors for the development of pediatric and adolescent obesity.

The Effects of Melatonin on Cognition and Αβ load in an Alzheimer’s Disease Mouse Model

AbstractBackgroundThe neurohormone melatonin is released from the pineal gland and is an endogenous antioxidant and free radical scavenger that regulates sleep/wake cycle and circadian rhythm. Decline of nocturnal melatonin secretion with severe sleep disturbance has been consistently reported in Alzheimer’s Disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. However, exogenous melatonin supplementation can reduce Αβ neurotoxicity and formation while improving cognitive performance and sleep quality.MethodIn this study, the long‐term influence of melatonin on behavioral and neuropathological changes were evaluated in the 5xFAD mouse model, when treatment was started in adolescence. After ∼20 weeks of orally administered melatonin (10 mg/kg), Morris water maze behaviour was assessed in 54 mice, followed by Aβ42 quantification in hippocampal tissue.ResultOverall, transgenic mice showed impaired learning, and a significant increase in Aβ42 plaque load, replicating previous results with this strain. Melatonin marginally improved learning by decreasing distance travelled in the Morris water maze and slightly decreasing Aβ42 concentration in the hippocampus. These results support the hypothesis that long‐term melatonin supplementation may be beneficial at early stages of the disease process and should be explored more fully.ConclusionAbnormal accumulation of neurotoxic forms of Αβ occur in brain regions involved in the regulation of sleep in AD patients and the disturbed regulation of sleep that occurs early in the disease may contribute to cognitive decline by decreasing Αβ clearance. In contrast to conventional antioxidants, melatonin crosses the blood‐brain barrier, is relatively devoid of toxicity, and constitutes a straight‐forward potential therapeutic candidate in AD treatment.

O031 Nocturnal melatonin secretion in post-treatment breast cancer patients: a preliminary study

Abstract Purpose Breast-cancer patients frequently report of poor sleep-quality. Although the pathophysiology is unclear, circadian-sleep misalignment is a plausible mechanism. We compared nocturnal melatonin-secretion, a circadian rhythm marker, in post-menopausal, post-treatment (≥12-months) female breast-cancer patients (BCG), with post-menopausal female controls with no history of cancer (CG) Methods We recruited 6 BCG and 10 CG from Westmead Hospital breast-cancer outpatient clinic or hospital-staff community, respectively. Participants completed the Pittsburgh Sleep Quality Index (PSQI; >5 PSQI-score=poor sleep-quality) and ~7 days of home-actigraphy (Philips Actiwatch-2, Philips Respironics, USA) to ascertain habitual bed-time (HBT). Later, participants completed an overnight, in-laboratory study, with saliva sampled (n=13) at regular intervals under strict dim-light conditions (<1 lux). Salivary-melatonin concentrations were quantified via radioimmunoassay (University of Adelaide). We measured 1) clock-time when salivary-melatonin concentrations reached 4pg/mL (melatonin onset-[DLMO-4pg/ml]) and 2) time-interval between HBT and DLMO-4pg/ml (indicates circadian-sleep misalignment-[PAR-DLMO]). Data were expressed as median [interquartile range], and compared using 2-sided Mann Whitney U-tests. p<0.05 was considered significant. Results BCG and CG had similar ages (62.5 [59.5–67.3] vs. 58.5 [54.0–66.3] yrs, respectively; p=0.23). Compared with CG, BCG had higher PSQI-scores (8.50 [5.25–10.75] vs. 4.00 [3.75–5.50] a.u.; p=0.07), but similar HBT (22:49 [21:46-23:38] vs. 22:17 [21:59-22:21] h:min; p=0.26). BCG had later DLMO-4pg/ml (20:46 [20:01-22:03] vs. 18:23 [17:55-20:07] h:min; p=0.03) and shorter PAR-DLMO (1.43 [0.96–2.38] vs. 3.63 [2.18–3.90] hrs; p=0.09), than CG. Conclusion Preliminary data indicate BCG had poorer sleep-quality, delayed melatonin onset, and altered circadian-sleep alignment; compared with CG. We speculate disrupted nocturnal melatonin-secretion potentially influences poor sleep-quality reported by breast-cancer patients.

A combination of melatonin and moderate-intensity aerobic exercise improves pancreatic beta-cell function and glycemic homeostasis in type 2 diabetic model of animals

Nocturnal melatonin secretion is important for preservation of ß-cell mass and function. Knowing that type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia caused by the elevated resistance of peripheral tissues to insulin, reduction in pineal melatonin and disturbances of insulin secretion by pancreatic ß-cells. In this context, exercise is considered one of the most valuable non-pharmacological approaches for treatment of T2DM. Considering the beneficial role of melatonin on glycemic metabolism in physical exercise, we investigated the effects of moderate-intensity aerobic exercise plus melatonin on glycemic homeostasis, the morphology and architecture of pancreas in spontaneous T2DM animals [Goto-Kakizaki (GK) rats]. The results confirmed that melatonin alone reduced the mass of epididymal white adipose tissue (WAT); however, only the combination of melatonin and physical exercise significantly reduced caloric intake, body weight, WAT and improved glucose tolerance and insulin sensitivity in T2DM rats. This combination also reduced apoptosis of cells in pancreatic islets. We observed either melatonin or the combination was able to reduce insulinemia. However, only the combination improved the morphology of the pancreatic islets. Thus, we conclude that in GK rats, melatonin plays a crucial role in the functionality of the pancreas to improve insulin sensitivity of peripheral tissues and, consequently, to maintain the glucose homeostasis. In addition, the combination is more efficiency to improve glucose tolerance and integrity of pancreatic islets in GK rats than melatonin alone.

Comparative Neurology of Circadian Photoreception: The Retinohypothalamic Tract (RHT) in Sighted and Naturally Blind Mammals.

The mammalian eye contains two systems for light perception: an image detecting system constituted primarily of the classical photoreceptors, rods and cones, and a non-image forming system (NIF) constituted of a small group of intrinsically photosensitive retinal ganglion cells driven by melanopsin (mRGCs). The mRGCs receive input from the outer retina and NIF mediates light entrainment of circadian rhythms, masking behavior, light induced inhibition of nocturnal melatonin secretion, pupillary reflex (PLR), and affect the sleep/wake cycle. This review focuses on the mammalian NIF and its anatomy in the eye as well as its neuronal projection to the brain. This pathway is known as the retinohypothalamic tract (RHT). The development and functions of the NIF as well as the knowledge gained from studying gene modified mice is highlighted. Furthermore, the similarities of the NIF between sighted (nocturnal and diurnal rodent species, monkeys, humans) and naturally blind mammals (blind mole rats Spalax ehrenbergi and the Iberian mole, Talpa occidentalis) are discussed in relation to a changing world where increasing exposure to artificial light at night (ALAN) is becoming a challenge for humans and animals in the modern society.

Modelling the effect of light through commercially available blue-blocking lenses on the human circadian system

ABSTRACT Clinical relevance Wearing blue-blocking lenses (BBLs) in the evening hours may not be effective in improving sleep quality. Optometrists need to be informed in prescribing BBLs by highlighting the consequences of their wear to the circadian system. Background Excessive exposure to artificial light, particularly at short wavelengths, during the evening, may disrupt normal nocturnal melatonin production, which is a natural process of the circadian rhythm and affect sleep quality. Current BBLs have been designed to limit blue-light exposure and may offer a means to minimise disruption to the circadian system. The purpose of this study was to evaluate the impact of BBLs on a normal sleep-wake circadian rhythm. Methods Seven different commercial brands of BBLs (Crizal Prevencia, Smart Blue Filter, Blu-OLP, Blue Control, UV++Blue Control, SeeCoat Blue UV and Blue Guardian) and powers (+2.00 D, −2.00 D and Plano) were evaluated by quantifying the degree to which they reduce light radiation from lamps and electronic devices. In particular, the non-linear circadian index and the circadian stimulus was determined for various light sources to establish changes in melatonin production that occur while viewing through different BBLs. Results A large difference was shown in the effectiveness of different BBL brands in reducing the spectral sensitivity of the circadian system. The BBL brand was shown to selectively affect the non-linear circadian index and circadian stimulus, particularly with those with transmittance profiles that block the most blue light having the lowest effect on the suppression of nocturnal melatonin secretion. Conclusion BBLs may not improve sleep quality, because they continue to allow the transmittance of blue light that may suppress nocturnal melatonin secretion and hence disrupt the normal sleep-wake circadian rhythm.

The Lighting Environment, Its Metrology, and Non-visual Responses.

International standard CIE S 026:2018 provides lighting professionals and field researchers in chronobiology with a method to characterize light exposures with respect to non-visual photoreception and responses. This standard defines five spectral sensitivity functions that describe optical radiation for its ability to stimulate each of the five α-opic retinal photoreceptor classes that contribute to the non-visual effects of light in humans via intrinsically-photosensitive retinal ganglion cells (ipRGCs). The CIE also recently published an open-access α-opic toolbox that calculates all the quantities and ratios of the α-opic metrology in the photometric, radiometric and photon systems, based on either a measured (user-defined) spectrum or selected illuminants (A, D65, E, FL11, LED-B3) built into the toolbox. For a wide variety of ecologically-valid conditions, the melanopsin-based photoreception of ipRGCs has been shown to account for the spectral sensitivity of non-visual responses, from shifting the timing of nocturnal sleep and melatonin secretion to regulating steady-state pupil diameter. Recent findings continue to confirm that the photopigment melanopsin also plays a role in visual responses, and that melanopsin-based photoreception may have a significant influence on brightness perception and aspects of spatial vision. Although knowledge concerning the extent to which rods and cones interact with ipRGCs in driving non-visual effects is still growing, a CIE position statement recently used melanopic equivalent daylight (D65) illuminance in preliminary guidance on applying “proper light at the proper time” to manipulate non-visual responses. Further guidance on this approach is awaited from the participants of the 2nd International Workshop on Circadian and Neurophysiological Photometry (in Manchester, August 2019). The new α-opic metrology of CIE S 026 enables traceable measurements and a formal, quantitative specification of personal light exposures, photic interventions and lighting designs. Here, we apply this metrology to everyday light sources including a natural daylight time series, a range of LED lighting products and, using the toobox, to a smartphone display screen. This collection of examples suggests ways in which variations in the melanopic content of light over the day can be adopted in strategies that use light to support human health and well-being.

Outdoor Light at Night and Breast Cancer Incidence in the Danish Nurse Cohort Study

Introduction: Breast cancer is the most common cancer type, and the most common reason for cancer-related deaths among women worldwide. Animal and epidemiologic studies suggest that exposure to light at night may contribute to increased breast cancer risk through circadian disruption, which involves a decrease in the nocturnal secretion of melatonin followed by disturbed estrogen regulation, however, epidemiological evidence is limited. In this study, we examined the association between exposure to residential outdoor light at night (LAN) and breast cancer incidence in the Danish Nurse Cohort Study. Methods: We followed 20,404 Danish nurses from 1993 or 1999 through 2012. LAN exposure was estimated using the US Defense Meteorological Satellite Program's (DMSP) Operational Linescan System. We collected LAN data (nW/cm2/sr) for 1996, 1999, 2000, 2002, 2004, 2005, and 2010, assigned at the subject's residence during the follow-up. Data on the incidence of breast cancer was obtained from the Danish Cancer Registry. We used time-varying Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for reproductive, lifestyle and environmental factors such as residential air pollution, road traffic noise, and greenspace. Results: Of the 20,490 women, 1,081 developed breast cancer in total during 339,633 person-years of follow-up. Based on the fully adjusted model of LAN exposure divided into quintiles, where the lowest LAN quintile was reference (0-13.6 nW/cm2/sr), we found an increase in breast cancer incidence at higher LAN levels: HR: 1.01 (95% CI: 0.83-1.23, p = 0.92), 1.08 (95% CI: 0.88-1.33, p = 0.44), 1.04 (0.83-1.30, p = 0.74), and 0.87 (95% CI: 0.66-1.15, p = 0.32) for the 2nd, 3rd, 4th, and 5th quintiles, respectively. Conclusion: There was a tendency, that higher levels of exposure to LAN were associated with a higher risk of breast cancer although the statistical significance was not observed.

A novel role for the pineal gland: Regulating seasonal shifts in the gut microbiota of Siberian hamsters

The gut microbiota plays a significant role in a variety of host behavioral and physiological processes. The mechanisms by which the gut microbiota and the host communicate are not fully resolved but include both humoral and direct neural signals. The composition of the microbiota is affected by internal (host) factors and external (environmental) factors. One such signal is photoperiod, which is represented endogenously by nocturnal pineal melatonin (MEL) secretion. Removal of the MEL signal via pinealectomy abolishes many seasonal responses to photoperiod. In Siberian hamsters (Phodopus sungorus), MEL drives robust seasonal shifts in physiology and behavior, such as immunity, stress, body mass, and aggression. While the profile of the gut microbiota also changes by season, it is unclear whether these changes are driven by pineal signals. We hypothesized that the pineal gland mediates seasonal alterations in the composition of the gut microbiota. To test this, we placed pinealectomized and intact hamsters into long or short photoperiods for 8weeks, collected weekly fecal samples, and measured weekly food intake, testis volume, and body mass. We determined microbiota composition using 16S rRNA sequencing (Illumina MiSeq). We found significant effects of treatment and time on the abundances of numerous bacterial genera. We also found significant associations between individual OTU abundances and body mass, testis mass, and food intake, respectively. Finally, results indicate a relationship between overall community structure, and body and testis masses. These results firmly establish a role for the pineal gland in mediating seasonal alterations in the gut microbiota. Further, these results identify a novel neuroendocrine pathway by which a host regulates seasonal shifts in gut community composition, and indicates a relationship between seasonal changes in the gut microbiota and seasonal physiological adjustments.

Serum Melatonin with Respect to Mental Health (Anxiety & Depression) Status of First Year M.B.B.S Students

Introduction: Melatonin is a pineal hormone secreted in circadian manner, with a peak during evening and night. Night-time light exposure is a powerful suppressor of nocturnal melatonin secretion. Dopamine and serotonin have complex relationship in melatonin synthesis and secretion. Reduced levels of melatonin have been associated with severe depression. Melatonin exhibits GABA-like effects may be responsible to reduce anxiety.
 Objectives: To determine the Serum Melatonin levels with respect to bedtime and its correlation with the severity of anxiety and depression. Also, to find the difference in anxiety score, depression score and serum melatonin level with respect to gender.
 Methods: A cross sectional study was done amongst first year medical students, and anxiety and depression score was calculated using Hamilton’s anxiety and depression scale. Estimation of Serum Melatonin was done on the fasting morning blood samples.
 Results and Conclusion: The present study shows that there is no significant difference in melatonin secretion in the students with late bedtime. With the increasing severity of the anxiety the serum melatonin was found to be lower, but the difference was not statistically significant. Similar results were observed with depression. The results shows non-significant higher anxiety and depression scores in females as compared to males. The study results also shows the significant high levels of melatonin in males as compared to females. Low melatonin levels in females may be attributed to high anxiety and depression in females.

0545 Bi-Layer Melatonin Tablet Provides Immediate and Extended Absorption to Address Primary Sleep Issues

Abstract Introduction Melatonin is a naturally-occurring hormone that functions in the regulation of the sleep-wake cycle. Exogenous melatonin has demonstrated utility for the induction and maintenance of sleep. Modulation of tablet dissolution rates can be achieved by strategically using binding agents in two layers to rapidly raise melatonin levels and sustain elevated levels over time to better emulate normal nocturnal melatonin secretion. Methods A randomized, double-blind, controlled cross-over study was conducted in healthy adults (n=18) to investigate the pharmacokinetics of a 4.5 mg melatonin bi-layer tablet with either prolonged-release (PR) or immediate-release (IR) characteristics. Blood samples were collected at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8 and 10 h post-ingestion and melatonin concentrations were quantified. Results The PR formulation had a lower maximum concentration (Cmax, p<0.002), but a longer time to reach maximum concentration (Tmax, p<0.001). Absorption rate constant (Ka) and terminal disposition rate constant (λ) were both lower in PR melatonin than the IR formulation (p<0.001), indicating slower absorption and elimination rates. These measures were consistent with significantly greater absorption (ta1/2, p<0.002) and elimination half-lives (t1/2, p<0.001) in the IR formulation compared to the PR formulation. Additionally, plasma melatonin concentrations reached pre-ingestion values by 8 h post-administration of the PR formulation, indicating that individuals sleeping for a recommended 7-9 hours will wake with normal melatonin levels, when taken an hour before bedtime. Conclusion Prolonged-release bi-layer melatonin tablet safely and effectively extends the absorption of exogenous melatonin compared to an immediate-release formulation. Support Pharmavite, LLC