Circadian Sleep-wake Rhythm Research Articles

Obstructive sleep apnea syndrome, orexin, and sleep-wake cycle: The link with the neurodegeneration.

Obstructive sleep apnea syndrome (OSAS) significantly affects the sleep-wake circadian rhythm through intermittent hypoxia and chronic sleep fragmentation. OSAS patients often experience excessive daytime sleepiness, frequent awakenings, and sleep fragmentation, leading to a disrupted circadian rhythm and altered sleep-wake cycle. These disruptions may exacerbate OSAS symptoms and contribute to neurodegenerative processes, particularly through the modulation of clock gene expression such as CLOCK, BMAL1, and PER. Emerging evidence connects OSAS to cognitive impairment and suggests that these changes may contribute to the development of neurodegenerative disorders such as Alzheimer disease, suggesting that OSAS could be a reversible risk factor for these conditions. Biomarkers, including melatonin and orexin, play crucial roles in understanding these mechanisms. In OSAS patients, melatonin, a marker of circadian rhythmicity, often shows altered secretion patterns that are not fully corrected by continuous positive airway pressure therapy. Orexin, which regulates the sleep-wake cycle, exhibits increased cerebrospinal fluid levels in OSAS patients, possibly due to compensatory mechanisms against sleep impairment and daytime sleepiness. These biomarkers highlight the intricate relationship between circadian rhythm disruptions and neurodegenerative risks in OSAS, emphasizing the need for further research and potential therapeutic strategies to mitigate these effects and improve patient outcomes.

Actigraphy-based assessment of circadian rhythmicity and sleep in patients with Usher syndrome type 2a: A case-control study.

This study aimed to improve our understanding of sleep problems as a comorbidity of hereditary deaf-blindness due to Usher syndrome type 2a. Fifteen patients with Usher syndrome type 2a with a conclusive genetic diagnosis and 15 unaffected controls participated in comprehensive sleep and activity assessments for 2 weeks, using the MotionWatch 8 actigraph and consensus sleep diary. Various sleep parameters including sleep opportunity window, sleep latency, sleep efficiency, and self-reported sleep quality were analysed. Non-parametric circadian rhythm analysis was performed to evaluate circadian rhythmicity. Additionally, regression analyses were conducted to study potential correlations between sleep parameters and patients' demographics and disease progression. Patients with Usher syndrome type 2a exhibited significantly longer sleep latency and lower self-reported sleep and rest quality compared with controls. Additionally, day-to-day variability of sleep efficiency and sleep latency were significantly higher in the patient population. Non-parametric circadian rhythm analysis revealed no significant differences in circadian rhythmicity. Regression analyses indicated that having Usher syndrome type 2a was a significant predictor of poor sleep outcomes. No clear correlations were found between the level of visual impairment and sleep parameters, suggesting that the negative effects of Usher syndrome type 2a on sleep manifest independently of the progressive visual impairment. These findings suggest that, while circadian sleep-wake rhythm remain intact, patients with Usher syndrome type 2a suffer from sleep disturbances that likely arise from factors beyond their progressive blindness. With sleep problems being a major risk factor for physical and mental health problems, we advocate that sleep problems should be recognized as a hallmark symptom of Usher syndrome type 2a, warranting in-depth research for potential targeted therapeutic interventions.

Subjective sleep quality in adolescent girls with menstrual disorders

Background. Menstrual irregularities occupy a leading place among gynecological diseases in girls. It is assumed that there is a connection between reproductive system disorders and sleep in adolescent girls, but to date this issue remains poorly understood.The aim. To study the subjective sleep quality of adolescent girls with irregular and regular menstrual cycles.Materials and methods. A survey of 461 teenage girls living in the city of Irkutsk and the Irkutsk region was conducted in the period from January 2023 to May 2024. Two groups were formed: group 1 – teenage girls with an irregular menstrual cycle (n = 121), group 2 – teenage girls without menstrual disorders (n = 340).Results. Adolescent girls with irregular menstrual cycles had sleep disturbances more often and longer, falling asleep later and taking longer, waking up later, poor sleep and daytime sleepiness. The average duration of sleep on weekdays, regardless of the nature of the menstrual cycle, was below the normal values for this age, which indicates a sleep deficit in adolescent girls.Conclusions. Poor sleep hygiene in adolescent girls, poor quality and short sleep cause disruption of the circadian rhythm that regulates the menstrual cycle. Increasing the duration and improving the quality of sleep are an important component of the formation and maintenance of reproductive health in adolescent girls. Further research is needed to better understand the complex relationships between circadian sleep-wake rhythms and the reproductive system in adolescent girls.

La melatonina nei disturbi del sonno in bambini e adolescenti con problemi neurocomportamentali

Melatonin, a neurohormone produced by the pineal gland, regulates the sleep-wake circadian rhythm. Sleep disorders are prevalent in children, especially those with neurodevelopmental disorders like autism and other neurodisabilities and affect about 50-75% of this population. The use of melatonin to improve sleep in this population has been debated for over 20 years, with recent reviews addressing its efficacy and safety. Melatonin significantly improves sleep latency and total sleep time in children with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and other neurodevelopmental disorders. However, its effectiveness in reducing night awakenings is limited. Short-term use shows no significant association with serious adverse effects, though mild side effects like headache, nausea, drowsiness, and mood changes are common. Long-term safety data are limited but suggest no significant impact on puberty onset or bone health. Dosing and timing of melatonin administration vary widely, and individualized treatment plans are recommended. The use of melatonin should be accompanied by behavioural interventions, and potential side effects should be monitored closely.

Orexin Receptor Antagonists for the Prevention and Treatment of Alzheimer's Disease and Associated Sleep Disorders.

Orexins/hypocretins are neuropeptides produced by the hypothalamic neurons, binding two G-protein coupled receptors (orexin 1 and orexin 2 receptors) and playing a critical role in regulating arousal, wakefulness, and various physiological functions. Given the high prevalence of sleep disturbances in Alzheimer's disease (AD) and their reported involvement in AD pathophysiology, the orexin system is hypothesized to contribute to the disease pathogenesis. Specifically, recent evidence suggests that orexin's influence may extend beyond sleep regulation, potentially affecting amyloid-β and tau pathologies. Dual orexin receptor antagonists (DORAs), namely suvorexant, lemborexant, and daridorexant, demonstrated efficacy in treating chronic insomnia disorder across diverse clinical populations. Considering their stabilizing effects on sleep parameters and emerging evidence of a possible neuroprotective role, these agents represent a promising strategy for AD management. This leading article reviews the potential use of orexin receptor antagonists in AD, particularly focusing on their effect in modulating disease-associated sleep disturbances and clinical outcomes. Overall, clinical studies support the use of DORAs to enhance sleep quality in patients with AD with comorbid sleep and circadian sleep-wake rhythm disorders. Preliminary results also suggest that these compounds might influence AD pathology, potentially affecting disease progression. Conversely, research on selective orexin receptor antagonists in AD is currently limited. Further investigation is needed to explore orexin antagonism not only as a symptomatic treatment for sleep disturbances, but also for its broader implications in modifying AD neurodegeneration, emphasizing mechanisms of action and long-term outcomes.

КЛИНИЧЕСКАЯ ЭФФЕКТИВНОСТЬ НЕГОРМОНАЛЬНЫХ МЕТОДОВ ТЕРАПИИ ПАТАЛОГИЧЕСКОГО КЛИМАКТЕРИЧЕСКОГО СИНДРОМА У ЖЕНЩИН

The purpose of the study is to study the clinical effectiveness of the dietary supplement "Menophen" in comparison with β-alanine in the treatment of menopausal symptoms in women in the perimenopausal, menopausal and postmenopausal periods. Menopausal syndrome is a complex of vegetative-vascular, psycho-emotional, metabolic-endocrine, vaginal, sexual and other disorders. According to domestic authors, vasomotor disorders such as hot flashes, lability of blood pressure and pulse, increased sweating, chills, which significantly reduce the quality of life of patients and disrupt the circadian sleep-wake rhythm, come to the fore. Today, menopausal women continue to work actively, but hot flashes and sleep disturbances significantly reduce their level of performance and increase the number of absences from sick leave by 82%, compared to women without hot flashes. At the same time, 87.5% of women refuse to use and prescribe MHT, expressing doubts about the safety of their use; the main fears of patients are weight gain and the development of oncological pathology. Treatment with the dietary supplement Menofen leads to a decrease in the number and severity of psycho-emotional, metabolic-endocrine and neurovegetative disorders in menopausal women.

Chinese formula Guben-Jiannao Ye alleviates the dysfunction of circadian and sleep rhythms in APP/PS1 mice implicated in activation of the PI3K/AKT/mTOR signaling pathway

Ethnopharmacological relevanceThe Chinese formula Guben-Jiannao Ye (GBJNY) formula has a long history of usage in traditional Chinese medicine (TCM) for the treatment of learning and memory disorders as well as senile insomnia. This formulation is derived from Sun Simiao's five tonic pills. Furthermore, modern pharmacological investigations have revealed its ability to improve cognitive impairment and ameliorate sleep-wake circadian rhythm disorders. However, the precise mechanism underlying its efficacy remains elusive. Aim of the studyThe current research explored the modulatory effects and possible mechanisms of GBJNY in circadian rhythm sleep-wake disorders and cognitive dysfunction in Alzheimer's disease using transcriptome sequencing and experimental validation. Materials and methodsThe LC-MS/MS tandem technology was utilized to qualitatively discern the active components present in GBJNY. The APP/PS1 mice received continuous treatment with GBJNY or Melatonin for 3 months. The learning and memory abilities of mice were assessed utilizing the Morris water maze (MWM) test, while sleep changes were studied utilizing the electroencephalogram (EEG) and electromyogram (EMG). Concurrently, mice's hippocampus clock gene rhythmicity was investigated. Subsequently, we employed HE staining, Golgi staining, and immunofluorescence to observe GBJNY's impact on synaptic damage and neuronal loss. We performed high-throughput sequencing to analyze the mRNA expression profiles of mice, aiming to identify differentially expressed genes (DEGs). Subsequently, we conducted GO and KEGG enrichment analyses to explore associated signaling pathways. Furthermore, we evaluated the expression levels of proteins involved in the PI3K/AKT/mTOR pathway and Aβ deposition in the hippocampus of mice. Through this comprehensive approach, we sought to elucidate and validate the potential mechanisms of action of GBJNY in APP/PS1 mice. ResultsResults showed 216 DEGs. Following this, we conducted GO enrichment and KEGG pathway analyses to delve deeper into the distinctions and fundamental functions of the mRNA target genes. The enrichment analysis underscored the prominence of the PI3K/Akt/mTOR signaling pathway as the most pivotal among them. Through in vivo experiments, it was further demonstrated that the administration of GBJNY enhanced memory and learning capacities in APP/PS1 mice. Additionally, GBJNY treatment resulted in alterations in the sleep-wake circadian rhythm, characterized by reduced wakefulness and an increase in non-rapid eye movement (NREM) sleep. Moreover, alterations in the peak expression of Per1, Per2, Clock, Cry1, Cry2, and Bmal1 mRNA were noted in the hippocampus of treated mice. Particularly noteworthy were the observed reductions in amyloid-beta (Aβ) deposition within the hippocampus, improvements in neuronal synaptic integrity, and upregulation of mTOR, Akt, and PI3K protein expression in the hippocampal region. These findings underscore the critical involvement of the PI3K/Akt/mTOR signaling pathway in mitigating disturbances in sleep-wake circadian rhythms. ConclusionsGBJNY enhanced the cognitive performance of APP/PS1 mice and altered clock gene expression patterns, alleviating sleep-wake circadian rhythm disruptions. The fundamental mechanism appears to be linked to the PI3K/Akt/mTOR pathway regulation, offering a foundation for potential clinical applications.

Excessive daytime sleepiness in myotonic dystrophy: a narrative review.

Excessive daytime sleepiness (EDS) is a common and debilitating symptom in both forms of myotonic dystrophy (DM), significantly impacting patients' quality of life. The review focuses on the purpose of examining the current understanding of EDS in these conditions, the difficulty in correctly accessing it, the recent findings related to its etiology and prevalence, and a summary of potential therapeutic implications. We conducted a comprehensive search through PubMed, selecting studies that provided significant insights into the mechanisms, prevalence, and management of EDS in DM1 and DM2. EDS is highly prevalent in both DM1 and DM2. Polysomnographic studies have revealed prominent dysregulation of REM sleep in DM1, suggesting a possible narcoleptic-like phenotype and alterations in NREM sleep that contributes to daytime sleepiness. Other factors have been proposed to explain EDS in DM1, including dysregulation of the sleep-wake circadian rhythm through nocturnal actigraphy analysis. The central origin of EDS is increasingly delineated supported by serotonin and orexin pathways dysfunction, and recent neuroradiological findings showing that in DM1 hippocampus volume was positively correlated with self-reported fatigue and somnolence. Sleep-disordered breathing and respiratory dysfunctions are prevalent in DM, their direct correlation with EDS remains complex and inconclusive, but respiratory evaluation should be recommended if obstructive sleep apneas or respiratory muscle dysfunctions are suspected. Drug interventions, such as modafinil and mexiletine, have shown promise in managing excessive daytime sleepiness and reducing myotonia without significant cardiac conduction effects. Enhancing EDS management in myotonic dystrophy is key to improving overall patient well-being.

Alteration of circadian sleep-wake rhythm and salivary melatonin secretion in idiopathic/isolated REM sleep behavior disorder: Preliminary evidence

Objective/BackgroundIdiopathic/isolated REM sleep behavior disorder (iRBD) is widely regarded as an early sign of neurodegeneration leading to synucleinopathies. While circadian rhythm alterations in iRBD have been preliminarily demonstrated, evidence on melatonin secretion patterns in this clinical condition is limited. To address this knowledge gap, this exploratory study aimed to integrate salivary melatonin measurement with actigraphic monitoring in individuals with iRBD and age-matched healthy controls (HC) under real-life conditions. MethodsParticipants diagnosed with iRBD and HC underwent clinical evaluation and wore an actigraph for seven days and nights. Salivary melatonin concentrations were measured at five time points during the last night of recording. Comparative analyses were conducted on clinical data, actigraphic parameters, and melatonin levels between the two groups. ResultsiRBD participants (n = 18) showed greater motor (p < 0.01) and non-motor symptoms (p < 0.001), alongside disruptions in circadian sleep-wake rhythm compared to HC (n = 10). Specifically, actigraphy revealed a delayed central phase measurement (p < 0.05), reduced activity during the most active hours (p < 0.001), and decreased relative amplitude (p < 0.05). Total salivary melatonin concentration was significantly lower in iRBD (p < 0.05), with a slight but non-significant phase delay in dim light melatonin onset. ConclusionsThis exploratory study highlights a dysregulation of circadian sleep-wake rhythm coupled with reduced melatonin secretion in iRBD. Future research could add to these preliminary findings to evaluate novel treatment approaches to regulate the sleep-wake cycle and elucidate the implications of circadian dysregulation in the conversion from iRBD to neurodegeneration.

Mechanism of GW117 antidepressant action: Melatonin receptor-mediated regulation of sleep rhythm

Alterations in circadian sleep patterns constitute a salient manifestation in major depressive disorder. GW117, an emergent antidepressant, functions as an agonist for melatonin 1 and melatonin 2 (MT1/MT2) receptors, in tandem with antagonism of the serotonin (5-HT) 2C receptor. The present investigation is dedicated to elucidating the role and underlying mechanisms by which GW117 ameliorates circadian sleep disruptions. Utilizing an adapted chronic unpredictable mild stress protocol, we induced a depressive-like phenotype and perturbed circadian rhythms in rodent models. Our methodological approach integrated quantitative polymerase chain reaction (qPCR) in real-time, enzyme-linked immunosorbent assay (ELISA), and immunoblotting techniques to probe alterations in the expression of core circadian genes and homeostatic sleep markers. The impact of GW117 was assessed across various dosages (10, 20, and 40 mg/kg) on these molecular signatures. In a parallel examination, we evaluated the influence of GW117 (administered at 15, 40, and 60 mg/kg) on the sleep patterns of healthy mice. The results showed that GW117 significantly improved sleep-wake circadian rhythms, altered sleep architecture, and shortened sleep latency. Furthermore, GW117 increased the expression of several clock genes in the hypothalamus of chronic unpredictable mild stress model rats and normal mice. It also regulated circadian biomarkers, including melatonin and cortisol. Based on our findings, we propose that the beneficial effects of GW117 on sleep rhythms may be due to the melatonin system-mediated activation of the Wnt/β-catenin signaling pathway.

Role of sleep in neurodegeneration: the consensus report of the 5th Think Tank World Sleep Forum.

Sleep abnormalities may represent an independent risk factor for neurodegeneration. An international expert group convened in 2021 to discuss the state-of-the-science in this domain. The present article summarizes the presentations and discussions concerning the importance of a strategy for studying sleep- and circadian-related interventions for early detection and prevention of neurodegenerative diseases. An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5years; discussed the current challenges in the field of relationships among sleep, sleep disorders, and neurodegeneration; and identified future priorities. Sleep efficiency and slow wave activity during non-rapid eye movement (NREM) sleep are decreased in cognitively normal middle-aged and older adults with Alzheimer's disease (AD) pathology. Sleep deprivation increases amyloid-β (Aβ) concentrations in the interstitial fluid of experimental animal models and in cerebrospinal fluid in humans, while increased sleep decreases Aβ. Obstructive sleep apnea (OSA) is a risk factor for dementia. Studies indicate that positive airway pressure (PAP) treatment should be started in patients with mild cognitive impairment or AD and comorbid OSA. Identification of other measures of nocturnal hypoxia and sleep fragmentation could better clarify the role of OSA as a risk factor for neurodegeneration. Concerning REM sleep behavior disorder (RBD), it will be crucial to identify the subset of RBD patients who will convert to a specific neurodegenerative disorder. Circadian sleep-wake rhythm disorders (CSWRD) are strong predictors of caregiver stress and institutionalization, but the absence of recommendations or consensus statements must be considered. Future priorities include to develop and validate existing and novel comprehensive assessments of CSWRD in patients with/at risk for dementia. Strategies for studying sleep-circadian-related interventions for early detection/prevention of neurodegenerative diseases are required. CSWRD evaluation may help to identify additional biomarkers for phenotyping and personalizing treatment of neurodegeneration.

Napping and circadian sleep-wake regulation during healthy aging.

Daytime napping is frequently reported among the older population and has attracted increasing attention due to its association with multiple health conditions. Here, we tested whether napping in the aged is associated with altered circadian regulation of sleep, sleepiness, and vigilance performance. Sixty healthy older individuals (mean age: 69 years, 39 women) were recruited with respect to their napping habits (30 nappers, 30 non-nappers). All participants underwent an in-lab 40-hour multiple nap protocol (10 cycles of 80 minutes of sleep opportunity alternating with 160 minutes of wakefulness), preceded and followed by a baseline and recovery sleep period. Saliva samples for melatonin assessment, sleepiness, and vigilance performance were collected during wakefulness and electrophysiological data were recorded to derive sleep parameters during scheduled sleep opportunities. The circadian amplitude of melatonin secretion was reduced in nappers, compared to non-nappers. Furthermore, nappers were characterized by higher sleep efficiencies and REM sleep proportion during day- compared to nighttime naps. The nap group also presented altered modulation in sleepiness and vigilance performance at specific circadian phases. Our data indicate that napping is associated with an altered circadian sleep-wake propensity rhythm. They thereby contribute to the understanding of the biological correlates underlying napping and/or sleep-wake cycle fragmentation during healthy aging. Altered circadian sleep-wake promotion can lead to a less distinct allocation of sleep into nighttime and/or a reduced wakefulness drive during the day, thereby potentially triggering the need to sleep at adverse circadian phase.

Effect of Smartphone Use on Sleep in Undergraduate Medical Students: A Cross-Sectional Study

Smartphone use, particularly at night, has been shown to provoke various circadian sleep–wake rhythm disorders such as insomnia and excessive daytime tiredness. This relationship has been mainly scrutinized among patient groups with higher rates of smartphone usage, particularly adolescents and children. However, it remains obscure how smartphone usage impacts sleep parameters in adults, especially undergraduate college students. This study sought to (1) investigate the association between smartphone use (actual screen time) and four sleep parameters: Pittsburgh sleep quality score (PSQI), self-reported screen time, bedtime, and rise time; (2) compare the seven PSQI components between good and poor sleep quality subjects. In total, 264 undergraduate medical students (aged 17 to 25 years) were recruited from the Government Doon Medical College, Dehradun, India. All participants completed a sleep questionnaire, which was electronically shared via a WhatsApp invitation link. Hierarchical and multinomial regression analyses were performed in relation to (1) and (2). The average PSQI score was 5.03 ± 0.86, with approximately one in two respondents (48.3%) having a poor sleep index. Smartphone use significantly predicted respondents’ PSQI score (β = 0.142, p = 0.040, R2 = 0.027), perceived screen time (β = 0.113, p = 0.043, R2 = 343), bedtime (β = 0.106, p = 0.042, R2 = 045), and rise time (β = 0.174, p = 0.015, R2 = 0.028). When comparing poor-quality sleep (PSQI ≥ 5) to good-quality sleep (PSQI &lt; 5), with good-quality sleep as the reference, except sleep efficiency and sleep medications (p &gt; 0.05), five PSQI components declined significantly: subjective sleep quality (β = −0.096, p &lt; 0.001); sleep latency (β = −0.034, p &lt; 0.001); sleep duration (β = −0.038, p &lt; 0.001); sleep disturbances (β = 1.234, p &lt; 0.001); and sleep dysfunction (β = −0.077, p &lt; 0.001). Consequently, public health policymakers should take this evidence into account when developing guidelines around smartphone use—i.e., the when, where, and how much smartphone use—to promote improved sleep behaviour and reduce the rate of sleep–wake rhythm disorders.

WED-431 - Circadian sleep-wake rhythms in non-alcoholic fatty liver disease

WED-431 - Circadian sleep-wake rhythms in non-alcoholic fatty liver disease

Association between Physical Activity Level and Sleep Quality in the Elderly

Introduction: The increase in a person’s age may cause degeneration in their physiological system, and these changes can affect various bodily functions, one of them is the sleep-wake cycle. The elderly usually have disturbed sleep-wake circadian rhythm that can cause sleep problems and decreased sleep quality. The action that can be done to increase sleep quality is doing physical activity.&#x0D; Methods: This research used cross-sectional study design. The respondents were people who reside in Komplek Taman Pulo Indah and Perumahan Aneka Elok aged 60 and older and were not included in the exclusion criteria (n = 204). The instruments used were the Baecke questionnaire to measure physical activity level and the PSQI questionnaire to measure sleep quality. Data analysis was done in univariate and bivariate using chi-square test with significance level of p&lt;0.005.&#x0D; Results: The prevalence of elderly with low physical activity levels and good sleep quality was 33.8%. Meanwhile, elderly with moderate physical activity levels and good sleep quality was 50%, and elderly with high physical activity levels and good sleep quality was 64,7%. Chi-square test was carried out and resulted in p = 0.002 (p&lt;0.005), which meant the null hypothesis was rejected. &#x0D; Conclusions: There was an association between physical activity level and sleep quality in the elderly.

Preliminary evidence that daily light exposure enhances the antibody response to influenza vaccination in patients with dementia

Enhancing lighting conditions in institutions for individuals with dementia improves their sleep, circadian rhythms and well-being. Here, we report first findings that exposure to brighter light during daytime may support the immune response to the annual influenza vaccination. Eighty older institutionalised patients suffering from dementia (54 women and 26 men) continuously wore an activity tracker for 8 weeks to assess individual light exposure and rest-activity cycles. We analysed the patients’ immune response from two blood samples taken before and 4 weeks after the annual influenza vaccination. Individual antibody concentrations to three influenza virus strains (H3N2, H1N1, IB) were quantified via hemagglutination inhibition assays. By quantifying individual light exposure profiles (including daylight), we classified the patients into a low and a high light exposure group based on a median illuminance of 392.6 lux. The two light exposure groups did not differ in cognitive impairment severity, age or gender distribution. However, patients in the high light exposure group showed a significantly greater circadian rest-activity amplitude (i.e., more daytime activity and less nighttime activity) along with a significantly greater antibody titer increase to the H3N2 vaccine than patients in the low light exposure group, despite similar pre-vaccination concentrations. Sufficient seroprotective responses to all three influenza virus strains were attained for ≥75% of participants. These data provide preliminary evidence for a potentially enhanced immune response in patients with dementia when they received more daily light. Future studies are needed to determine whether regular daily light exposure may have beneficial effects on the human immune system, either directly or via a stabilising circadian sleep-wake rhythms.

Attempted suicide by Melatonin overdose: Case report and literature review

IntroductionMelatonine (N-acetyl-5-methoxytryptamine) is an endogenous neurohormone produced by pineal gland. It is related to sleep-wake circadian rhythms, and nowdays it is sold without prescription as a “natural treatment” for sleep disorders. Most common side effects of melatonin overdose are drowsiness, dizziness, fatigue, headache, confusion, nightmare, hypotension, tachycardia and hypothermia. Supportive measures and control of vital signs are essential for an early discharge of the patient.ObjectivesTo present a case of an 42-year-old woman who was taken to the emergency department after voluntary ingestion of 60 tables of melatonin 2mg (Total amount 120mg), in a suicide attempt. To describe the most common side effects of melatonine overdose a the literature review.MethodsClinical case presentation and retrospective literature review.ResultsA 42-year-old woman who was taken to the emergency department after voluntary ingestion of 60 tables of melatonin 2mg (Total amount 120mg), about 1 hour before coming, in a suicide attempt. After clinical evalutation, gastric lavage was performed. ang 50g activated charcoal given. Drowiness and mild hypothermia (34ºC) was detected. After 12 hours of vital signs observation the patient was discharged and to psychiatry consultation, where depressive mood disorder and chronic insomnia was diagnosed.ConclusionsMelatonin is one of the least toxic medication. Most common side effects of overdose are drowsiness, dizziness, fatigue, headache, confusion, nightmare, hypotension, tachycardia and hypothermia. Supportive measures and control of vital signs are essential for the treatment.DisclosureNo significant relationships.

0262 Sleep-wake cycle circadian disruption after chronic alcohol intake in a rat model of anxiety

Abstract Introduction Alcohol intake can produce disruptions in sleep-wake cycle, including circadian alterations like phase shifts. Alcohol intake is increased in subjects with anxiety to diminish its symptoms. We have selectively bred two sublines from Sprague-Dawley rats that differs on its yawning frequency. The high-yawning (HY) rats have a mean of 20 yawns/h, whereas the low-yawning (LY) rats have only 2 yawns/hour. LY male rats had high anxiety-like behavior in standardized tests and high preference for alcohol intake. The aim of this study was to assess circadian disruption of sleep-wake cycle after chronic alcohol consumption. Methods We used 8 male rats from HY and LY at 3 months of age. All rats were kept in acrylic boxes with food pellets and purified water ad libitum under a light-dark cycle of 12:12 (lights on at 0700) and temperature of 21 ± 1 °C. All subjects were implanted for EEG, EMG and EOG recordings to characterize sleep-wake phases. A basal sleep-wake recording was obtained for 24 h. A second and third recording were made after a 7 days of alcohol administration as a single source of hydration (AL1) and a 3 week two-bottle choice alcohol preference protocol (AL2) were carried out. We used COSINOR analysis to determine phase and cycle alterations of sleep-wake circadian rhythm of all subjects. Results After alcohol intake, there was a significant difference only in the acrophases of awake periods (P&amp;lt;0.01) and slow wave sleep (SWS, P&amp;lt;0.001) in both AL1 and AL2 conditions for the HY subline, with a phase delay of 90 min for awake, 30 min for SWS and an advanced phase of 40 min for rapid eye movement sleep (REM) with respect to basal condition. In the case of LY subline, there was a significant difference only in SWS (P&amp;lt;0.001) and REM sleep (P&amp;lt;0.05) acrophases for both AL1 and AL2 conditions, with a phase delay of 7 h for wake, 40 min for SWS and 1 h for REM sleep. Conclusion It has been reported that alcohol disrupt circadian synchronization of the sleep-wake cycle, producing a general delay of SWS and REM sleep phases. Additionally, subjects with basal circadian disruptions are more susceptible to increase their intake of alcohol and other addictive drugs. So, LY male rats are an adequate model for higher susceptibility to alcohol intake. Support (If Any) Partially supported by PRONACES-CONACYT grant and VIEP-BUAP 2021 to CA in Neuroendocrinología (BUAP-CA-288). AFR is PhD on Physiological Sciences fellowship from CONACYT No. 926368

The two-process model of sleep regulation: Beginnings and outlook.

SummaryThe two‐process model serves as a major conceptual framework in sleep science. Although dating back more than four decades, it has not lost its relevance for research today. Retracing its origins, I describe how animal experiments aimed at exploring the oscillators driving the circadian sleep–wake rhythm led to the recognition of gradients of sleep states within the daily sleep period. Advances in signal analysis revealed that the level of slow‐wave activity in non‐rapid eye movement sleep electroencephalogram is high at the beginning of the 12‐light period and then declines. After sleep deprivation, the level of slow‐wave activity is enhanced. By scheduling recovery sleep to the animal's activity period, the conflict between the sleep–wake‐dependent and the circadian influence resulted in a two‐stage recovery pattern. These experiments provided the basis for the first version of the two‐process model. Sleep deprivation experiments in humans showed that the decline of slow‐wave activity during sleep is exponential. The two‐process model posits that a sleep–wake‐dependent homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C). At present, homeostatic and circadian facets of sleep regulation are being investigated at the synaptic level as well as in the transcriptome and proteome domains. The notion of sleep has been extended from a global phenomenon to local representations, while the master circadian pacemaker has been supplemented by multiple peripheral oscillators. The original interpretation that the emergence of sleep may be viewed as an escape from the rigid control imposed by the circadian pacemaker is still upheld.

Ramadan Fasting and NCDs-Example of the Diabetes.

Although Ramadan lasts only for 1 month each year, it can be accompanied by significant changes in: both energy and nutritional intake; in the diet composition; in the working hours; and the usual way of life. The majority of practitioners consume two meals, one after sunset (Iftar) and one before dawn (Sohor). During this month, it is also an opportunity to share a meal with family and friends, a period of highly intensified socialization. In parallel with the nutritional changes brought about by this unique pattern of fasting in Ramadan, other metabolic and physiological changes may occur, such as fluctuations in body weight and/or disturbance in the quantity and quality of the sleep-wake circadian rhythm. In the verses of the Qur'an, the exemption from fasting in certain situations such as illness is clearly stated. Despite this religious tolerance, many faithful who are eligible for the exemption observe the fast of Ramadan either for the spiritual aspect it provides by performing it, by religious guilt or to mark a normalization in the Muslim community for fear of the gaze of others. The world is experiencing an increase in the emergence of non-communicable diseases (NCDs); leading cause of the global mortality. Environmental and behavioral risk factors related to lifestyle, such as smoking, excessive alcohol consumption, unhealthy diet, and sedentarity have a causal association with NCDs. Other factors, such as genetic and physiological factors may also be associated (overweight, high blood pressure, dyslipidemia). Diabetes is one of the highest prevalent NCDs in the world and it continues increasing year by year. This chronic disease can lead to significant potential complications (degenerative, dermatological, and acute) to the patient's health. This requires an individual and appropriate care, both dietetic and therapeutic and over the long term will at best make it possible to sensitize the diabetic patient to the adverse effects related to his disease and thus improve its quality of life. Performing the Fast of Ramadan for a diabetic is a common situation. Diabetes is the only chronic disease widely studied in relation to Ramadan fasting. In the literature, many studies have investigated the effects of Ramadan intermittent fasting on diabetic patients. This article aims to provide a general overview and highlight if there are many effect of Ramadan fasting on diabetes, as an example of a NCDs.