Melatonin Profiles Research Articles

Light intensity and suppression of nocturnal plasma melatonin in Arctic charr (Salvelinus alpinus)

The problem of early sexual maturation among farmed Arctic charr and other salmonids can be effectively reduced by 24 h light overwinter, provided it is bright enough to over-ride interference from the natural daylength cycle. To determine the threshold light intensity to suppress the nocturnal elevation of plasma melatonin, three groups of individually tagged fish (n = 26–28/group ca. 1040 g) were reared on 12 h light: 12 h dark (LD 12:12) and subjected to nighttime light intensities of either 50–65, 0.1–0.3 or 0 (control) lux for five months (November to April). Daytime light intensity was 720–750 lx. Diel plasma melatonin profiles in both November and April were similar; mean daytime levels ranged from 20 to 100 pg/ml, and nighttime levels were inversely proportional to light intensity. In the control group at 0 lx, plasma melatonin increased about four-fold after lights-off, ranging between 320 and 430 pg/ml. Nighttime light intensity of 0.1–0.3 lx halved plasma melatonin levels to 140–220 pg/ml, and 50–65 lx further reduced the levels to one quarter of the control group, 68–108 pg/ml. Among the lit groups, daytime plasma melatonin levels were about 20–30 pg/ml, significantly lower than the nocturnal levels suggesting the diel hormonal rhythm was not completely abolished. Fish grew steadily from about 1100 g to 1600 g between November and April, independent of light intensity (P = .67). Overall, the study demonstrated the sensitivity of pineal melatonin hormone to different light intensities in Arctic charr.

Circadian rhythms of melatonin and peripheral clock gene expression in idiopathic REM sleep behavior disorder

ObjectiveTo evaluate changes in the expression of clock genes and melatonin levels in patients with idiopathic REM sleep behavior disorder (RBD) as a potential early stage of synucleinopathies. MethodsWe assessed the rhythmicity of circadian clock genes using real time-quantitative polymerase chain reaction and 24-h blood melatonin profiles using radio-immunoassay in 10 RBD patients and nine age-matched controls. ResultsThe RBD patients did not show circadian rhythmicity for clock genes Per2, Bmal1, and Nr1d1 but the rhythmicity of Per 1 remained, and the amplitude of Per3 was diminished. The 24-h melatonin rhythm did not differ between RBD patients and healthy control subjects. Melatonin profile in RBD patients was delayed by 2 h compared to controls, the habitual sleep phases were phase delayed by about 1 h, however no phase shift occurred in any of the clock genes studied. The control group had stable acrophases of melatonin rhythms of approximately 5 h whereas the RBD patients had a more dispersed range over 11 h. ConclusionsOur results suggest that RBD could be associated with altered expression of clock genes and delayed melatonin secretion. Thus, we argue that circadian system dysregulation could play a role in RBD.

Circadian Rhythm Disturbances in the Blind.

Sleep timing, quantity, and quality are controlled by homeostatic and circadian systems. Circadian clock systems are present in all cells and organs and their timing is determined by a transcriptional-translational feedback loop of circadian genes. Individual cellular clocks are synchronized by the central body clock, situated in the suprachiasmatic nucleus, which communicates with them through humoral and neural signals including melatonin. The circadian system controls both the circadian period: (i.e., the length of the intrinsic clock), but also the circadian phase (i.e., the clock timing). An important determinant of the circadian system is light exposure. In most humans, the circadian period is slightly longer than 24h and without regular resetting it tends to drift, leading to progressively later bedtimes and wake times and a tendency to cycle though periods of normal and abnormal sleep. Blind patients are thus at an increased risk of abnormal circadian function. The purpose of this article is to review recent research and clinical management of circadian rhythm disorders in blind patients. Blind patients can present delayed and advanced sleep phase disorders but the most common abnormality in totally blind patients without light perception is non-24-hour sleep-wake disorder (N24SWD). This is rare in the general population but may affect up to 50% of blind patients without light perception. The diagnosis of a circadian rhythm disorder in the blind is complex. New screening tools have been developed but actigraphy and repeated melatonin profiles over 24h remain essential. Circadian disorders in the blind are frequent, especially in the patients without light perception. They require accurate diagnosis in order to target treatment. Determining the precise nature of a sleep disorder in blind patients with a suspected circadian rhythm abnormality is complex and requires a detailed clinical history with sleep diaries and the use of actigraphy and melatonin profiles.

Diurnal melatonin profile in patients with pituitary adenomas

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

0117 Impact of Light Exposure during Sleep on Cardiometabolic Function

Artificial light exposure is increasingly widespread, particularly at night. Light exposure at night is known to impact circadian rhythms such as melatonin and sleep, and disturbances in these rhythms have been shown to affect cardiometabolic function. As such, the aim of this study was to test the hypothesis that light exposure at night during sleep negatively impacts cardiometabolic outcomes, possibly via disruptions to sleep architecture and melatonin profiles. Twenty healthy adults 18–40 years of age were randomized into Dark-Dark (DD) or Dark-Light (DL) groups and run in parallel for a three day and two night stay. Participants had 8 hours of sleep opportunity each night starting at habitual bedtime determined from one week of actigraphy with sleep diary. The DL group (n=10, 2 males, ages 26.61 ± 4.64 years, BMI 23.25 ± 3.94 kg/m^2) slept in the dark < 3 lux on Night 1 and slept in overhead room light of 100 lux on Night 2, while the DD group (n=10, 4 males, ages 26.78 ± 5.15 years, BMI 24.25 ± 3.71 kg/m^2) slept in the dark <3 lux on both Nights 1 and 2. Overnight polysomnography and hourly blood sampling for melatonin were collected on both nights. Oral glucose tolerance tests were performed on both mornings following sleep in the dark or 100 lux of light. Repeated measures ANOVA were performed between groups (DL vs. DD) with Day (Day 1 vs Day 2) and Time of Day as within-subject factors. Homeostatic model assessment of insulin resistance values were significantly higher (p<0.05) in the morning following sleep in the light (DL group) compared to sleep in the dark (DD group). This effect was primarily due to increased insulin levels for DL compared to DD group, for which there was a trend for group by day effect (p<0.09). A single night of light exposure during sleep acutely impacts insulin resistance, and chronic overnight exposure may have long-term effects on metabolic function. This research was supported National Institutes of Health grants 5T32HL7909, P01AG11412, and 8UL1TR000150-05.

Simultaneous release of melatonin and methylprednisolone from an injectable in situ self-crosslinked hydrogel/microparticle system for cartilage tissue engineering.

Recently, injectable hydrogel/microparticle systems have so considered for tissue engineering and regenerative medicine. In this study, we produced an injectable in situ self-crosslinked hydrogel/microparticle system for simultaneous dual drug delivery. First, melatonin conjugated chitosan microparticle loaded with methylprednisolone (MCC-MP) microparticle was fabricated by the covalent linkage of melatonin to chitosan by N-hydroxysuccinimide (NHS)1-Ethyl-3-(3-dimethylamino propyl)-carbodiimide (EDC) followed by an ionic gelation of MCC and MP using tripolyphosphate (TPP). Second, the hydrogel was prepared by the connection between the aldehyde group of alginate oxide (AD) and the amine group belonging to carboxymethyl chitosan (CMC) via Schiff base reaction. Finally, microparticle was incorporated into the AD-CMC hydrogel to produce a hydrogel/microparticle system. Hydrogel/microparticle was assessed by many techniques including microscopy, spectroscopy, particle size measurements, mechanical analysis, injectability, rheological analyses to ascertain hydrogel/microparticle properties. The biological assays of mesenchymal stem cells (MSCs) culture, 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), acridine orange/propidium iodide (AO/PI), and 4, 6-diamidino-2-phenylindole (DAPI) to assess cell viability and dimethylmethylene blue (DMMB) to evaluate proteoglycan content were done. The release profiles of melatonin and MP showed acceptable release after 60 and 20 days, respectively. The hydrogel/microparticle system has the ability to sustain cells alive. A higher rate of proteoglycan content was observed in hydrogel/microparticle as compared with hydrogel. With appropriate biocompatibility and adequate properties, this system can be a proper alternative for cartilage tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1932-1940, 2018.

Melatonin Treatment in Patients with Burning Mouth Syndrome: A Triple-Blind, Placebo-Controlled, Crossover Randomized Clinical Trial.

To evaluate the efficacy of melatonin compared to placebo in reducing pain associated with burning mouth syndrome (BMS), as well as side effects of treatment and effects on sleep quality, anxiety, and serum and salivary melatonin levels. In this triple-blind, randomized clinical trial, 20 BMS patients (mean age ± standard deviation: 64.4 ± 11.5 years; range: 35 to 82 years) were enrolled to receive melatonin (12 mg/day) or placebo for 8 weeks in a crossover design. After treatment, changes in pain from baseline were ascertained by patient self-assessment with a verbal category scale and a visual analog scale. Secondary outcomes included evaluation of changes in sleep quality and anxiety. Data were subjected to analysis of variance (ANOVA), Fisher exact test, paired t test, Wilcoxon signed rank test, or chi-square test, as appropriate. Melatonin was not superior to placebo in reducing pain. Melatonin significantly improved anxiety scores, though without strong clinical relevance. Independent of treatment, sleep quality did not significantly change during the trial, although melatonin slightly increased the number of hours slept. After active treatment, the mean ± standard error serum melatonin level peaked at 1,520 ± 646 pg/mL. A generally safe pharmacologic profile of melatonin was observed, and the placebo and melatonin treatments resulted in similar adverse effects. Within the limitations of this study, melatonin did not exhibit higher efficacy than placebo in relieving pain in BMS patients.

Meagre's melatonin profiles under captivity: circadian rhythmicity and light sensitiveness.

The present study reveals the first characterization of the plasma melatonin rhythms of the meagre (Argyrosomus regius) under aquaculture conditions. Melatonin levels were monitored during a 24h cycle under a photoperiod of 16L:8D and under constant darkness (DD), respectively to characterize the daily rhythm of this indoleamine and to test its endogenous origin. Besides, to identify which light intensities are perceived as night or day by this species, the degree of inhibition of nocturnal melatonin production caused by increasing intensities of light was tested (3.3, 5.3, 10.5, and 120μW/cm2), applying 1h light pulses at Mid-Dark. The result for melatonin daily rhythm in plasma showed a typical profile: concentration remained low during all daytime points, increasing greatly during dark points, with maximum values at 16:00 and 22:00h, zeitgeber time. Under DD conditions, the plasma melatonin profile persisted, with a similar acrophase but with a lower amplitude between subjective day and night periods, indicating this rhythm as being endogenously driven. Moreover, meagre seemed to be very sensitive to dim levels of illumination during the night, since an intensity of just 3.3μW/cm2 inhibited melatonin production. However, only the pulse of 5.3μW/cm2 caused a melatonin drop till daytime concentrations. Thus, the threshold of light detection by the pineal organ was suggested as being located between 3.3 and 5.3μW/cm2. Such results are an added value for this species biology knowledge, and in consequence to its adaptation to aquaculture conditions, allowing the improvement of culture husbandry protocols.

Comparison of Melatonin Profile and Alertness of Firefighters with Different Work Schedules.

Introduction:A two-shift work schedule with different rotations is common among firefighters in Iranian petrochemical companies. This study compared salivary melatonin and sleepiness on the last night before turning to day shift at 19:00, 23:00, 3:00, and 7:00 among petrochemical firefighters (PFFs) working seven and four consecutive night shifts.Methods:Sixty four PFFs working in the petrochemical industry were selected. To measure melatonin, saliva samples were taken, whereas the KSS index was used to assess sleepiness. Chi-square and independent samples t-test were carried out to analyze the data, and generalized linear model (GLM) was employed to determine the effect of confounding factors such as lighting and caffeine.Results:The levels of melatonin at 3:00 and 7:00, and the overall changes during the shift in the two shift patterns under the study were different (P < 0.05). Sleepiness was significantly different only at 3:00 in the two studied shift patterns, while the effects of lighting and caffeine on melatonin changes were not significant (P > 0.05).Conclusion:It seems that a slow shift rotation is better because it reduces the secretion of melatonin (hence reducing sleepiness during the night) and changes the peak of melatonin secretion to the daytime, which is a sign of adaptation.

Melanopsin System Dysfunction in Smith-Magenis Syndrome Patients.

Smith-Magenis syndrome (SMS) causes sleep disturbance that is related to an abnormal melatonin profile. It is not clear how the genomic disorder leads to a disturbed synchronization of the sleep/wake rhythm in SMS patients. To evaluate the integrity of the intrinsically photosensitive retinal ganglion cell (ipRGC)/melanopsin system, the transducers of the light-inhibitory effect on pineal melatonin synthesis, we recorded pupillary light responses (PLR) in SMS patients. Subjects were SMS patients (n = 5), with molecular diagnosis and melatonin levels measured for 24 hours and healthy controls (n = 4). Visual stimuli were 1-second red light flashes (640 nm; insignificant direct ipRGC activation), followed by a 470-nm blue light, near the melanopsin peak absorption region (direct ipRGC activation). Blue flashes produce a sustained pupillary constriction (ipRGC driven) followed by baseline return, while red flashes produce faster recovery. Pupillary light responses to 640-nm red flash were normal in SMS patients. In response to 470-nm blue flash, SMS patients had altered sustained responses shown by faster recovery to baseline. SMS patients showed impairment in the expected melatonin production suppression during the day, confirming previous reports. SMS patients show dysfunction in the sustained component of the PLR to blue light. It could explain their well-known abnormal melatonin profile and elevated circulating melatonin levels during the day. Synchronization of daily melatonin profile and its photoinhibition are dependent on the activation of melanopsin. This retinal dysfunction might be related to a deficit in melanopsin-based photoreception, but a deficit in rod function is also possible.

Exposure to Night-Time Traffic Noise, Melatonin-Regulating Gene Variants and Change in Glycemia in Adults.

Traffic noise has been linked to diabetes, with limited understanding of its mechanisms. We hypothesize that night-time road traffic noise (RTN) may impair glucose homeostasis through circadian rhythm disturbances. We prospectively investigated the relationship between residential night-time RTN and subsequent eight-year change in glycosylated hemoglobin (ΔHbA1c) in 3350 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA), adjusting for diabetes risk factors and air pollution levels. Annual average RTN (Lnight) was assigned to participants in 2001 using validated Swiss noise models. HbA1c was measured in 2002 and 2011 using liquid chromatography. We applied mixed linear models to explore RTN–ΔHbA1c association and its modification by a genetic risk score of six common circadian-related MTNR1B variants (MGRS). A 10 dB difference in RTN was associated with a 0.02% (0.003–0.04%) increase in mean ΔHbA1c in 2142 non-movers. RTN–ΔHbA1c association was modified by MGRS among diabetic participants (Pinteraction = 0.001). A similar trend in non-diabetic participants was non-significant. Among the single variants, we observed strongest interactions with rs10830963, an acknowledged diabetes risk variant also implicated in melatonin profile dysregulation. Night-time RTN may impair glycemic control, especially in diabetic individuals, through circadian rhythm disturbances. Experimental sleep studies are needed to test whether noise control may help individuals to attain optimal glycemic levels.

Differential impact in young and older individuals of blue-enriched white light on circadian physiology and alertness during sustained wakefulness

We tested the effect of different lights as a countermeasure against sleep-loss decrements in alertness, melatonin and cortisol profile, skin temperature and wrist motor activity in healthy young and older volunteers under extendend wakefulness. 26 young [mean (SE): 25.0 (0.6) y)] and 12 older participants [(mean (SE): 63.6 (1.3) y)] underwent 40-h of sustained wakefulness during 3 balanced crossover segments, once under dim light (DL: 8 lx), and once under either white light (WL: 250 lx, 2,800 K) or blue-enriched white light (BL: 250 lx, 9,000 K) exposure. Subjective sleepiness, melatonin and cortisol were assessed hourly. Skin temperature and wrist motor activity were continuously recorded. WL and BL induced an alerting response in both the older (p = 0.005) and the young participants (p = 0.021). The evening rise in melatonin was attentuated under both WL and BL only in the young. Cortisol levels were increased and activity levels decreased in the older compared to the young only under BL (p = 0.0003). Compared to the young, both proximal and distal skin temperatures were lower in older participants under all lighting conditions. Thus the color temperature of normal intensity lighting may have differential effects on circadian physiology in young and older individuals.

Daily profiles of serum and gastrointestinal melatonin in response to daytime or night-time supply of tryptophan-rich diet in carp (Catla catla)

Influences of daytime (~10:00 h) or night-time (~22:00 h) supply of L-tryptophan (Trp)-rich diet on daily rhythm features of melatonin and arylalkylamine-N-acetyltransferase (AANAT) protein (key regulator of melatonin biosynthesis) in gastrointestinal (gut) tissue extracts, and melatonin in serum were studied in carp (Catla catla). Analysis of obtained data revealed that the mesor and amplitude values of both melatonin and AANAT in gut tissue-extracts were higher in daytime-fed fish than those supplied with food at night, and their acrophase varied from ~2 h in the daytime-fed carp to ~10 h in night-time-fed fish. Notably, initiation of stimulatory response of melatonin and AANAT in gut to Trp-rich diet varied from ~2 h (following food supply in day) to ~6 h (after food supply during night). However, in either case, their elevated levels were maintained for ~12 h. Trp-rich diet also caused increase in serum melatonin levels, and the duration of such response varied with the time of food supply. Collectively, present study not only demonstrates the role of Trp-rich diet as a potential inducer of gut melatoninergic system and modulator of daily serum melatonin profiles, but underlines the importance of the time of food supply as a determining factor of its influence as well.

Field Study of Effects of Night Shifts on Cognitive Performance, Salivary Melatonin, and Sleep.

BackgroundNight shift work is associated with many problems such as sleep deprivation, sleepiness, decreased cognitive performance, increased human errors, and fatigue. This study set out to measure cognitive performance, melatonin rhythms, and sleep after different consecutive night shifts (7 vs. 4) among control room operators (CORs).MethodsThe participants included 60 CORs with a mean age of 30.2 years (standard deviation, 2.0) from a petrochemical complex located in Southern Iran. Cognitive performance was assessed using the n-back task and continuous performance test. To evaluate melatonin, saliva was collected and tested by enzyme-linked immunosorbent assay. To assess sleep and sleepiness, the Pittsburgh Sleep Quality Index and Karolinska Sleepiness Scale were used, respectively.ResultsIndividuals who worked 7 consecutive night shifts had a significantly better cognitive performance and sleep quality than those who worked 4 consecutive night shifts. However, salivary melatonin profile and sleepiness trend were not affected by shift type.ConclusionThe main duty of CORs working night shifts at the studied industry included managing safety-critical processes through complex displays; a responsibility that demands good cognitive performance and alertness. It is suggested that an appropriate number of consecutive night shifts in a rotating shift system should be planned with the ultimate aim of improving CROs performance/alertness and enhancing safety.

Profile and reproductive roles of seminal plasma melatonin of boar ejaculates used in artificial insemination programs.

Melatonin (MLT) is present in seminal plasma (SP) of mammalian species, including pigs, and it is credited with antioxidant properties. This study aims to identify the sources of variation and the role of boar SP MLT on sperm quality and functionality and in vivo fertilizing ability of liquid-stored semen doses used in AI programs. The SP MLT was measured using an ELISA kit in a total of 219 ejaculates collected from 76 boars, and reproductive records of 5,318 AI sows were recorded. Sperm quality was assessed according to motility (computer-aided sperm analysis) and viability (cytometry evaluation). Sperm functionality was assessed according to the cytometric determination of intracellular HO generation, total and mitochondrial O production, and lipid peroxidation in liquid AI semen samples stored at 17°C over 144 h. The concentration of SP MLT differed among seasons ( < 0.01) and day length periods ( < 0.001) of the year, demonstrating that the ejaculates collected during the increasing day length period (9.80 ± 1.38 pg/mL, range: 2.75-21.94) had lower SP MLT concentrations than those collected during the decreasing day length period (16.32 ± 1.67 pg/mL, range: 5.02-35.61). The SP MLT also differed ( < 0.001) among boars, among ejaculates within boar, and among portions within the ejaculate, demonstrating that SP from the first 10 mL of sperm-rich ejaculate fraction (SRF) exhibited lower MLT concentrations than post-SRF. The SP MLT was negatively related ( < 0.001) to mitochondrial O production in viable sperm. The SP MLT did not differ among AI boars ( = 14) hierarchically grouped according to high and low fertility outcomes. In conclusion, SP MLT concentration in AI boars varies depending on the season of ejaculate collection and differs among boars, ejaculates within boar, and portions within ejaculate. The SP MLT may act at the mitochondrial level of sperm by reducing the generation of O. However, this antioxidant role of SP MLT was not reflected in sperm quality or in vivo fertility outcomes of AI semen doses.

Melatonin and cortisol secretion profile in patients with pineal cyst before and after pineal cyst resection

A pineal cyst is a benign affection of the human pineal gland on the borderline between pathology and normality. Only a small percentage of patients present with symptoms and a surgical treatment is indicated in highly selected cases. A melatonin secretion in patients with a pineal cyst before and after a pineal cyst resection has not been studied yet and the effect of surgery on human metabolism is unknown. The present study examined melatonin, cortisol and blood glucose secretion profiles perioperatively in a surgical group of 4 patients. The control group was represented by 3 asymptomatic patients with a pineal cyst. For each patient, 24-h circadian secretion curves of melatonin, cortisol and glycemia were acquired. An analysis of melatonin profiles showed an expected diurnal pattern with the night peak in patients before the surgery and in the control group. In contrast, melatonin levels in patients after the surgery were at their minimum throughout the whole 24-h period. The cortisol secretion was substantially increased in patients after the surgery. Blood glucose sampling showed no statistically significant differences. Clinical results demonstrated statistically significant headache relief measured by Visual Analogue Scale in patients after the surgery. Despite the small number of examined patients, we can conclude that patients with a pineal cyst preserved the physiological secretion of the hormone melatonin while patients who underwent the pineal cyst resection experienced a loss of endogenous pineal melatonin production, which equated with pinealectomy. Surprisingly, cortisol secretion substantially increased in patients after the surgery.

Sleep during an Antarctic summer expedition: new light on "polar insomnia".

Sleep complaints are consistently cited as the most prominent health and well-being problem in Arctic and Antarctic expeditions, without clear evidence to identify the causal mechanisms. The present investigation aimed at studying sleep and determining circadian regulation and mood during a 4-mo Antarctic summer expedition. All data collection was performed during the continuous illumination of the Antarctic summer. After an habituation night and acclimatization to the environment (3 wk), ambulatory polysomnography (PSG) was performed in 21 healthy male subjects, free of medication. An 18-h profile (saliva sampling every 2 h) of cortisol and melatonin was assessed. Mood, sleepiness, and subjective sleep quality were assessed, and the psychomotor vigilance task was administered. PSG showed, in addition to high sleep fragmentation, a major decrease in slow-wave sleep (SWS) and an increase in stage R sleep. Furthermore, the ultradian rhythmicity of sleep was altered, with SWS occurring mainly at the end of the night and stage R sleep at the beginning. Cortisol secretion profiles were normal; melatonin secretion, however, showed a severe phase delay. There were no mood alterations according to the Profile of Mood States scores, but the psychomotor vigilance test showed an impaired vigilance performance. These results confirm previous reports on "polar insomnia", the decrease in SWS, and present novel insight, the disturbed ultradian sleep structure. A hypothesis is formulated linking the prolonged SWS latency to the phase delay in melatonin.NEW & NOTEWORTHY The present paper presents a rare body of work on sleep and sleep wake regulation in the extreme environment of an Antarctic expedition, documenting the effects of constant illumination on sleep, mood, and chronobiology. For applied research, these results suggest the potential efficiency of melatonin supplementation in similar deployments. For fundamental research, these results warrant further investigation of the potential link between melatonin secretion and the onset of slow-wave sleep.

Profile and reproductive roles of seminal plasma melatonin of boar ejaculates used in artificial insemination programs

Profile and reproductive roles of seminal plasma melatonin of boar ejaculates used in artificial insemination programs

Melatonin and Angelman Syndrome: Implications and Mathematical Model of Diurnal Secretion.

The main aim of the study was to compare the melatonin rhythms in subjects with Angelman syndrome (n = 9) and in children with (n = 80) and without (n = 40) epilepsy (nonepileptic patients diagnosed with peripheral nerve palsies, myopathy, and back pain) using our mathematical model of melatonin circadian secretion. The characteristics describing the diurnal hormone secretion such as minimum melatonin concentration, release amplitude, phase shift of melatonin release, and sleep duration as well as the dim light melatonin onset (DLMO) of melatonin secretion and the γ shape parameter allow analyzing the fit and deducing about how much the measured melatonin profile differs from a physiological bell-shaped secretion. The estimated sleep duration and phase shift of melatonin release as well as the DMLO offsets at 25% and 50% relative thresholds are the key characteristic of Angelman syndrome children. As revealed from the γ shape parameter, the melatonin secretion profiles are disturbed in majority of the AG subjects revealing rather a triangular course instead of the bell-like one.

The effect of blue-blocking and neutral intraocular lenses on circadian photoentrainment and sleep one year after cataract surgery.

To compare the long-term effect on circadian photoentrainment and sleep in patients implanted with neutral and blue-blocking intraocular lenses 1year after cataract surgery. Randomized, controlled trial involving 67 patients with age-related cataract. Intervention was cataract surgery with implantation of either a neutral or a blue-blocking intraocular lens (IOL). Main outcome was activation of the intrinsically photosensitive retinal ganglion cells (ipRGC) measured by chromatic pupillometry. The circadian rhythm was analysed by 24-hr melatonin profiles and actigraphy; the latter was also used to determine objective sleep quality. The Pittsburgh Sleep Quality Index determined subjective sleep quality. One year after surgery, peak melatonin concentration was 3.3pg/ml (95% CI, 2-5.5) corresponding to 50% lower for the participants allocated to blue-blocking IOLs compared with participants allocated to neutral IOLs. Compared with preoperative levels, the ipRGC response had increased by 13.7% (95% confidence interval [CI], 3.2-22.6) 1year after surgery. Objective sleep quality was also improved as the time of wakefulness after sleep onset had improved by 5min (95% CI, 1-10) for the entire population while sleep efficiency had increased by two percentage points (95% CI, 0.42-3.65) although exclusively, for the participants allocated to blue-blocking IOLs. Blue-blocking IOLs increased sleep efficiency but lowered nocturnal melatonin secretion compared with neutral IOLs. Cataract surgery improved the response of ipRGCs and sleep quality. However, the effect of cataract surgery on sleep quality may be unrelated to circadian photoentrainment.