Claude Gronfier

Melatonin is a hormone synthesized by the pineal gland from tryptophan as a precursor and serotonin as an intermediate. It is secreted during the night and displays a peak around 3 a.m., depending on the individual chronotype. This rhythm is generated by an endogenous biological clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus and entrained to the light/dark cycle (circadian rhythm). The roles of melatonin are numerous, but this hormone is described as a messenger of nighttime to the body, a modulator of circadian rhythmicity in mammals (including humans), and a regulator of seasonal rhythms in photoperiodic animals. Melatonin, as a hormone message controlled by the central circadian clock, distributes temporal cues to the complex network of peripheral circadian clocks found in a multitude of target structures. This message favors the adaptation of the entire organism to the photoperiod. In this way, melatonin plays the role of an endogenous synchronizer capable of reinforcing the circadian rhythms, stabilizing them and maintaining their phase relationships (internal synchronization), which contributes to a physiological coherence. In fact, melatonin is not the sleep hormone, but it reinforces the contrast between day/night and activity/sleep. Further, exogenous administration of melatonin favors sleep onset (soporific effect) and influences the endogenous melatonin rhythm (advancing or delaying it according to the time of administration; a so-called chronobiotic activity) via the circadian clock. This chronobiotic activity is the pharmacological basis for the treatment of dysrhythmia (jet lag syndrome, delayed-sleep phase syndrome, non-24 circadian sleep disorder in blind people, etc.).

Hunger and satiety are interoceptions involved in the control of food intake. How they change across the day and from one day to the next, as well as their relationships with physiological parameters, remain poorly understood. In a five-day laboratory study, 20 healthy male participants (24.2 +/- 3.3 years) were given 3 meals per day (breakfast, lunch, dinner), at times based on each individual's internal time. Subjects had a 8-h sleep opportunity at night recorded by polysomnography, during which time they were exposed to 4 different light intensities (0, 3, 8, or 20 lux). Hunger and satiety were assessed before and after each meal. Heart rate was measured continuously and glucose levels were sampled every 15 minutes. We found that: 1) hunger and satiety varied dynamically with the lowest levels at breakfast and the highest at lunch and dinner (p < 0.001 ); 2) Hunger and satiety were subject-dependent, and keep stable across the five experimental days; 3) heart rate was higher after than before meals (p < 0.0001), and higher around breakfast than dinner; 4) Glycemia before and after meals was respectively stable throughout the day and over the five-day study; 5) interoception was correlated with fluctuations in heart rate, glucose levels and sleep duration. Overall, our results reveal that hunger and satiety perception are individual characteristics. To better understand the role of interoception in food intake control, both hunger and satiety should be measured separately in their respective states.

The International Society for Bipolar Disorders (ISBD) Chronobiology and Chronotherapy Task Force conducted a comprehensive review to deliver concise evidence-based recommendations on the use of bright light therapy (BLT) for bipolar disorder (BD). Adjunctive BLT is likely an efficacious acute treatment for bipolar depression as implicated by higher quality evidence. The position of maintenance BLT for relapse prevention awaits further investigation. Protocols of effective BLT in BD are similar to parameters indicated for treatment of seasonal and non-seasonal major depressive disorder. Anti-manic prophylaxis (especially for BD-I) and clinical monitoring are recommended with initiation of and ongoing light treatment. Administer BLT daily, preferably in the morning or at mid-day. If mornings are prohibitive, then mid-day exposure, implemented to avoid excessively early wake times, is an acceptable alternative. Informed by the literature, target 30 min/day of BLT exposure. Patients wary of emergent hypomania or partial responders, can initiate 15 min/day and increase by 15 min each week to full response (or 30-60 min/day by the fourth week). Consider patient centred outcome assessments to evaluate mood response, safety and side effects. Clinical improvement is typically observed within 1-2 weeks, with response/remission expected by 4-6 weeks. Integration of BLT with other chronotherapeutic strategies may enhance long-term efficacy.

Sleep regulation depends on the complex interplay between homeostatic and circadian processes synchronized by the light/dark cycle. Sleep is also directly regulated by light via the retinal inputs to the preoptic area (POA). Although the light-responsive POA neurons project to several wake-promoting structures, including histaminergic neurons in the tuberomammillary nucleus (TMn), there is no functional evidence for their involvement in light-induced sleep. To bridge this gap, we used histidine decarboxylase (HDC, the histamine-synthetizing enzyme) knockout mice (HDC−/−, n=7) and hM4Di-HDC-cre mice (HDC+/+, n=8) subjected to an ultradian light/dark protocol (LD 1h:1h over 24h), and another group of hM4Di-HDC-cre mice (n=8) exposed to a 1-h light pulse. We found that light pulses during the biological night enhanced slow wave sleep and increased cortical EEG power in the delta range (0.5-3Hz), and that these effects were significantly attenuated both in HDC−/− (83 vs 23 min/6h, p=0.005) under LD 1h:1h condition and in hM4Di-HDC-cre mice after acute chemogenetic silencing of histamine neurons by the DREADD ligand deschloroclozapine (15 vs 6 min/h, p=0.0016) under a 1-h light pulse. In addition, the sleep-inducing effect of light was circadian dependent, with the strongest effect at the beginning and end of the night but no effect at all during the biological day in HDC+/+mice. Our study provides functional evidence that the acute sleep-inducing effects of light on sleep require histamine neurotransmission in mice.

Hunger and satiety, as two main interoceptions alternating around each meal, participate in the control of food intake. However, the temporal characteristics of these sensations across different times of the day and from one day to another, as well as their relationship with other physiological parameters, remain poorly understood.In a five-day laboratory study, 20 healthy male participants (24.2 ± 3.3) received three meals (breakfast, lunch, dinner) at wake (WT) + 50 min, WT + 320 min, WT + 720 min, based on each individual’s habitual sleep/wake times. Subjects were not allowed naps during the 16-h day, and their 8-h sleep at night was recorded with polysomnography. Questionnaires investigating hunger and satiety were given before and after each meal. Heart rate was measured continuously and glucose levels every 15 min. We found that: 1) hunger and satiety of each individual showed a dynamic daily variation, with minimal hunger and satiety at breakfast and increasing levels throughout the day, reaching a maximum at lunch (p < 0.01), and no difference between lunch and dinner; 2) the perception levels of hunger and satiety was subject dependent, and the levels were stable in each subject across the 5 experimental days (p < 0.0001); 3) heart rate and glucose levels were significantly influenced by the day of the study, meal time, and internal state (pre/post-meal); 4) sleep duration and structure did not correlate with daytime interoception.Altogether, our results reveal that hunger and satiety are two individual interoception modalities that are both dynamic during the day and remarkably stable throughout the week (in this 5-day experimental study). They suggest that hunger and satiety are robust in controlling food intake, and that good sleep optimizes energy balance, promotes optimal metabolic function, and maintains regular eating patterns.

The spectral distribution is a fundamental property of non-monochromatic optical radiation. It is commonly used in research and practical applications when studying how light interacts with matter and living organisms, including humans. In the field of lighting, misconceptions about the spectral distribution of light are responsible for unfounded claims, which pervade the scientific and technical communities. Starting from the definition of the spectral distribution, this paper describes the ambiguities and errors associated with a purely graphical analysis of the spectral distribution. It also emphasizes the importance of considering the particle nature of light in research involving both visual and non-visual effects, which implies using the spectral distribution expressed in the photon system of units, a system that has been seldom used in lighting research for historical reasons. The authors encourage lighting engineers and researchers to determine which system is best suited to their work and then proceed with the correct use of spectral distributions and of spectral weighting functions for applications involving optical radiation.

Sleeping problems are prevalent among children and adolescents, often leading to frequent consultations with pediatricians. While cognitive-behavioral therapy has shown effectiveness, especially in the short term, there is a lack of globally endorsed guidelines for the use of pharmaceuticals or over-the-counter remedies in managing sleep onset insomnia. An expert panel of pediatric sleep specialists and chronobiologists met in October 2023 to develop practical recommendations for pediatricians on the management of sleep onset insomnia in typically developing children. When sleep onset insomnia is present in otherwise healthy children, the management should follow a stepwise approach. Practical sleep hygiene indications and adaptive bedtime routine, followed by behavioral therapies, must be the first step. When these measures are not effective, low-dose melatonin, administered 30–60 min before bedtime, might be helpful in children over 2 years old. Melatonin use should be monitored by pediatricians to evaluate the efficacy as well as the presence of adverse effects.    Conclusion: Low-dose melatonin is a useful strategy for managing sleep onset insomnia in healthy children who have not improved or have responded insufficiently to sleep hygiene and behavioral interventions. What is Known:• Pediatric insomnia is a common disorder and impacts children's emotional, behavioral, and cognitive functioning, as well as parents' sleep and daytime functioning.• There is no consensus in Europe on the management of sleep onset insomnia and the use of melatonin in typically developing children. What is New:• A group of European experts has compiled a set of recommendations for the management of insomnia, developing a step-by-step approach.• Sleep hygiene, behavioral strategies, and finally low-dose melatonin represent valid strategies for managing sleep onset insomnia.

The ovarian cycle has a well-established circa-monthly rhythm, but the mechanisms involved in its regularity are unknown. Is the rhythmicity driven by an endogenous clock-like timer or by other internal or external processes? Here, using two large epidemiological datasets (26,912 cycles from 2303 European women and 4786 cycles from 721 North American women), analyzed with time series and circular statistics, we find evidence that the rhythmic characteristics of the menstrual cycle are more likely to be explained by an endogenous clock-like driving mechanism than by any other internal or external process. We also show that the menstrual cycle is weakly but significantly influenced by the 29.5-day lunar cycle and that the phase alignment between the two cycles differs between the European and the North American populations. Given the need to find efficient treatments of subfertility in women, our results should be confirmed in larger populations, and chronobiological approaches to optimize the ovulatory cycle should be evaluated.

Discomfort glare is a common visual sensation, which is generally reported when being exposed to a brighter lit environment. In certain clinical conditions, this sensation is abnormally amplified, and is commonly named photophobia. Despite the frequent appearance of this sensation in everyday life or in pathological conditions, the underlying mechanisms remain poorly understood. We show here, in highly controlled laboratory constant routine conditions, that light-induced discomfort glare is rhythmic over the 24-hour day. We reveal a strong circadian drive, with a sinusoidal rhythmicity, with maximal discomfort glare in the middle of the night and minimal in the afternoon. We also find a modest sleep-related homeostatic drive of visual discomfort, with a linear increase in discomfort glare over 34 hours of prolonged wakefulness. Our study reveals that discomfort glare is primarily driven by the ipRGC pathway, and that mid and/or long wavelengths cones are involved as well. The 6.5-hour phase lag between the rhythms of photoreceptors’ sensitivity, assessed through pupillary light reflex, and of glare discomfort, suggests two independent underlying mechanisms. In conclusion, our findings highlight the need to take time-of-day and biological rhythmicity into account in the evaluation of light-induced discomfort glare. Apprehending these mechanisms may help understand photophobia in clinical populations, such as in migraine patients, and should be taken into account to optimize light quality at home and at the workplace, both for day and night work.

Discomfort glare is a common visual sensation, which is generally reported when being exposed to a brighter lit environment. In certain clinical conditions, this sensation is abnormally amplified, and is commonly named photophobia. Despite the frequent appearance of this sensation in everyday life or in pathological conditions, the underlying mechanisms remain poorly understood. We show here, in highly controlled laboratory constant routine conditions, that light-induced discomfort glare is rhythmic over the 24-hour day. We reveal a strong circadian drive, with a sinusoidal rhythmicity, with maximal discomfort glare in the middle of the night and minimal in the afternoon. We also find a modest sleep-related homeostatic drive of visual discomfort, with a linear increase in discomfort glare over 34 hours of prolonged wakefulness. Our study reveals that discomfort glare is primarily driven by the ipRGC pathway, and that mid and/or long wavelengths cones are involved as well. The 6.5-hour phase lag between the rhythms of photoreceptors' sensitivity, assessed through pupillary light reflex, and of glare discomfort, suggests two independent underlying mechanisms. In conclusion, our findings highlight the need to take time-of-day and biological rhythmicity into account in the evaluation of light-induced discomfort glare. Apprehending these mechanisms may help understand photophobia in clinical populations, such as in migraine patients, and should be taken into account to optimize light quality at home and at the workplace, both for day and night work.