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Circadian rhythm disruptions have been implicated in numerous health issues, including cognitive decline and the exacerbation of neurodegenerative diseases, like Alzheimer disease (AD). Brain-derived neurotrophic factor (BDNF), vital for neuronal plasticity and cognitive function, is regulated by the circadian clock and exerts protective effects against AD. Thus, we investigated the impact of circadian rhythm disorders (CRDs) on cognitive impairment and explored the underlying neurobiological mechanisms by assessing BDNF and amyloid-β (Aβ) levels. We divided male C57BL/6 mice into three groups (n = 30): a control group (normal 12/12 hour light-dark cycle) and two CRD model groups (3/3 and 22/22 hour cycles, respectively). After 12 weeks, we assessed cognitive functions using the Morris water maze. Following behavioral tests, hippocampal levels of BDNF and Aβ were quantified using enzyme-linked immunosorbent assays. CRDs significantly impaired learning and memory, as evidenced by longer times to reach and find the platform in the CRD groups (p < 0.01). Furthermore, BDNF levels were notably decreased and Aβ levels increased in the CRD groups compared with the control group (p < 0.01). Thus, CRDs elicit cognitive impairment by reducing BDNF levels and increasing Aβ deposition in the hippocampus. [ABSTRACT FROM AUTHOR]

Abstract Circadian rhythm disorder (CRD) is closely associated with hair regression and shedding, but whether this risk can be transmitted to the offspring is unknown. Whether Pu‐erh tea, with alleviating effects of CRD‐mediated syndrome, can act on the transmission of alopecia risk to offspring is also unproven. Here, we obtained CRD parental mice offspring and found that CRD‐mediated alopecia risk can be transmitted to offspring, especially male offspring. Parental consumption of Pu‐erh tea, especially in females or both parents, reduced the risk of CRD‐mediated alopecia transmitted to offspring by inhibiting subcutaneous fat accumulation (downregulation of Rab18, fat‐specific protein 27 (Fsp27), and perilipin 1 (Plin1)), reducing oxidative stress and inflammation in skin tissue (NADPH oxidase 4 (NOX4)/ nuclear factor kappa‐B (NF‐κB)), balancing androgen and hair growth factor release (hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin‐like growth factor 1 (IGF‐1)), and restoring hair follicle DNA repair function (upregulation of Ku70, 8‐Oxoguanine DNA glycosylase 1 (OGG1), and Rad51). Transcriptomic analysis further clarified that the mechanism stemmed from the upregulation of gene expression in pathways such as the Wnt, Hippo, and other signaling pathways.

With the rapid development of society and changing lifestyles, people often encounter circadian rhythm disorder (CRD). Although tea active components have shown promise in improving CRD, a comprehensive comparison of different types of tea in improving CRD is still lacking, and the mechanism of regulating CRD-induced metabolic disorders remained unclear. This study selected three representative teas (Green tea, black tea, and dark tea) and compared the ameliorative effects of different teas on CRD-induced metabolic dysfunction. Furthermore, tea intervention improved the metabolic syndrome associated with CRD mainly through decreasing relative abundance of BSH-producing microbes, increasing conjugated bile acids (BAs) that act in an antagonistic manner on intestinal farnesoid X receptor (FXR), and promoting elimination of BAs via the feces. Our results shed light into the mechanisms behind the ameliorative effect of tea intervention on metabolic dysfunction caused by CRD, and suggest that the gut microbiota-bile acid-FXR axis may be potential therapies.

Objective To investigate whether discontinuous sleep supplementation can reduce myocardial ischemia-reperfusion injury in diabetic rats aggravated by circadian rhythm disorder. Methods The rats were injected intra-peritoneal with 1% streptozotocin(STZ) 30 mg/kg combined with high-fat and high-glucose diet to replicate diabetic model. Forty diabetic rats were randomly divided into four groups with 10 in each: sham surgery group(Sham group),ischemia-reperfusion group(I/R group), in which the left anterior descending coronary artery(LDA) was ligated for thirty minutes and reperfusion for 2 h,circadian rhythm disorder group(Crd group,24 h daily light and food),discontinuous sleep supplementation group(Dss group,every 3 hours of illumination and 1.5 hours break at night). We analyzed the myocardial infarct size (by 2,3,5-triphenyltetrazolium chloride staining),determined serum creatine kinase-myoglobin(CK-MB) activity and cardiac troponin Ⅰ(cTnⅠ) concentrations; the expression level of BMAL1 and REV-ERBα was determined by Western blot. Results Compared to the sham group, the I/R group showed a significantly increased in myocardial infarct size, serum CK-MB activity and cTnⅠ concentration. The expression of the myocardial biological clock gene BMAL1 was down-regulated, while the expression of REV-ERBα was up-regulated(P＜0.05).Compared to the I/R group, the Crd group showed a significantly increase in myocardial infarct size, serum CK-MB activity and cTnⅠ concentration. The expression of the myocardial biological clock gene BMAL1 was down-regulated, while the expression of REV-ERBα was up-regulated (P＜0.05).Compared to the Crd group, Dss group showed a significantly decrease in the myocardial infarct size, serum cTn concentration and CK-MB activity.Furthermore,there was an increased protein expression of BMAL1 and a decrease of REV-ERBα(P＜0.05). Conclusions Discontinuous sleep supplementation can reduce myocardial ischemia-reperfusion injury in diabetic rats aggravated by circadian rhythm disorder.

Abstract Background Circadian rhythm is crucial to the function of the immune system. Disorders of the circadian rhythm can contribute to inflammatory diseases such as Ulcerative colitis (UC). This Mendelian Randomization (MR) analysis applies genetic tools to represent the aggregated statistical results of exposure to circadian rhythm disorders and UC and its comorbidities, allowing for causal inferences. Methods Summary statistics of protein, DNA methylation and gene expression quantitative trait loci in individuals of European ancestry (pQTL, mQTL, and eQTL, respectively) were used. Genetic variants located within or near 152 circadian clock-related genes and closely related to circadian rhythm disorders were selected as instrumental variables. Causal relationships with UC and its comorbidities were then estimated through employed Summary data-based Mendelian Randomization (SMR) and Inverse-Variance-Weighted MR (IVW-MR). Results Through preliminary SMR analysis, we identified a potential causal relationship between circadian clock-related genes and UC along with its comorbidities, which was further confirmed by IVW-MR analysis. Our study identified strong evidence of positive correlation involving seven overlapping genes (CSNK1E, OPRL1, PIWIL2, RORC, MAX, PPP5C, and AANAT) through MWAS and TWAS in UC, four overlapping genes (OPRL1, CHRNB2, FBXL17, and SIRT1) in UC with PSC, and three overlapping genes (ARNTL, USP7, and KRAS) in UC with arthropathy. Conclusions This SMR study demonstrates the causal effect of circadian rhythm disorders in UC and its comorbidities. Furthermore, our investigation pinpointed candidate genes that could potentially serve as drug targets.

Abstract Background Patients with mental disorders have a higher prevalence of sleep problems than the general population. Sleep problems may include insomnia, circadian rhythm disorders, or hypersomnia. A transdiagnostic approach combining cognitive behavioral therapy for insomnia (CBT-I) with chronotherapy addressing a broad range of sleep problems has shown promising results in a limited number of studies. The aim of the study is to investigate the efficacy of a transdiagnostic sleep intervention for patients with sleep problems comorbid to bipolar disorder, unipolar depression, or attention deficit disorders. The primary hypothesis is that the intervention improves sleep quality compared with a control group. The secondary hypotheses are that the intervention increases subjective and objective sleep efficiency, reduces sleep onset latency, wake after sleep onset, number of awakenings, and severity of insomnia; and that it improves well-being, personal recovery, work ability, and consumption of sleep medication compared with a control group. Methods The study is a randomized controlled trial enrolling 88 outpatients with bipolar disorder, major depression, or attention deficit disorder with symptoms of various sleep problems (insomnia, circadian rhythm disorders, or hypersomnia). Patients are allocated to either an intervention group receiving six sessions of transdiagnostic sleep treatment or to a control group receiving a single session of sleep hygiene education. Assessments are made at baseline, at week two, and after 6 weeks in both groups. Actigraphy is performed continuously throughout the 6-week study period for all patients. The primary outcome is changes in the subjective appraisal of sleep quality (Pittsburgh Sleep Quality Index). The secondary outcomes are changes in sleep efficiency, sleep onset latency, wake after sleep onset, number of nocturnal awakenings (based on actigraph and sleep diary data), changes in insomnia severity (Insomnia Severity Index), well-being (WHO-5 Well-Being Index), personal recovery (INSPIRE-O), work ability (Work Ability Index), and consumption of sleep medication (sleep-diaries). Discussion The study was initiated in 2022 and the inclusion period will continue until mid-2024. The results may have implications for the development and implementation of additional treatment options for patients with mental disorders and comorbid sleep problems. Trial registration ClinicalTrials.gov. NCT05406414. Registered on June 6, 2022.

People with a diagnosis of schizophrenia often have poor sleep, even when their psychotic symptoms are relatively well managed. This includes insomnia, sleep apnoea, hypersomnia, and irregular or non-24 h sleep–wake timing. Improving sleep would better support recovery, yet few evidence-based sleep treatments are offered to this group. This paper presents a mixed methods feasibility and acceptability study of Light–Dark and Activity Rhythm Therapy (L-DART). L-DART is delivered by an occupational therapist over 12 weeks. It is highly personalisable to sleep phenotypes and circumstances. Ten participants with schizophrenia spectrum diagnoses and sleep problems received L-DART; their sleep problems and therapy goals were diverse. We measured recruitment, attrition, session attendance, and adverse effects, and qualitatively explored acceptability, engagement, component delivery, adherence, activity patterns, dynamic light exposure, self-reported sleep, wellbeing, and functioning. Recruitment was ahead of target, there was no attrition, and all participants received the minimum ‘dose’ of sessions. Acceptability assessed via qualitative reports and satisfaction ratings was good. Adherence to individual intervention components varied, despite high participant motivation. All made some potentially helpful behaviour changes. Positive sleep and functioning outcomes were reported qualitatively as well as in outcome measures. The findings above support testing the intervention in a larger randomised trial ISRCTN11998005.

Severe traumatic brain injury (TBI) can result in persistent complications, including circadian rhythm disorder, that substantially affect not only the injured people, but also the mood and social interactions with the family and the community. Pyroptosis in GFAP-positive astrocytes plays a vital role in inflammatory changes post-TBI. We determined whether VX-765, a low molecular weight caspase-1 inhibitor, has potential therapeutic value against astrocytic inflammation and pyroptosis in a rodent model of TBI plus hemorrhagic shock and resuscitation (HSR). A weight-drop plus bleeding and refusion model was used to establish traumatic exposure in rats. VX-765 (50 mg/kg) was injected via the femoral vein after resuscitation. Wheel-running activity was assessed, brain magnetic resonance images were evaluated, the expression of pyroptosis-associated molecules including cleaved caspase-1, gasdermin D (GSDMD), and interleukin-18 (IL-18) in astrocytes in the region of anterior hypothalamus, were explored 30 days post-trauma. VX-765-treated rats had significant improvement in circadian rhythm disorder, decreased mean diffusivity (MD) and mean kurtosis (MK), increased fractional anisotropy (FA), an elevated number and branches of astrocytes, and lower cleaved caspase-1, GSDMD, and IL-18 expression in astrocytes than TBI + HSR-treated rats. These results demonstrated that inhibition of pyroptosis-associated astrocytic activations in the anterior hypothalamus using VX-765 may ameliorate circadian rhythm disorder after trauma. In conclusion, we suggest that interventions targeting caspase-1-induced astrocytic pyroptosis by VX-765 are promising strategies to alleviate circadian rhythm disorder post-TBI. [ABSTRACT FROM AUTHOR]

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Background: Patients with mental disorders have a higher prevalence of sleep problems than the general population. Sleep problems may include insomnia, circadian rhythm disorders, or hypersomnia. A transdiagnostic approach combining cognitive behavioral therapy for insomnia (CBT-I) with chronotherapy addressing a broad range of sleep problems has shown promising results in a limited number of studies. The aim of the study is to investigate the efficacy of a transdiagnostic sleep intervention for patients with sleep problems comorbid to bipolar disorder, unipolar depression, or attention deficit disorders. The primary hypothesis is that the intervention improves sleep quality compared with a control group. The secondary hypotheses are that the intervention increases subjective and objective sleep efficiency, reduces sleep onset latency, wake after sleep onset, number of awakenings, and severity of insomnia; and that it improves well-being, personal recovery, work ability, and consumption of sleep medication compared with a control group. Methods: The study is a randomized controlled trial enrolling 88 outpatients with bipolar disorder, major depression, or attention deficit disorder with symptoms of various sleep problems (insomnia, circadian rhythm disorders, or hypersomnia). Patients are allocated to either an intervention group receiving six sessions of transdiagnostic sleep treatment or to a control group receiving a single session of sleep hygiene education. Assessments are made at baseline, at week two, and after 6 weeks in both groups. Actigraphy is performed continuously throughout the 6-week study period for all patients. The primary outcome is changes in the subjective appraisal of sleep quality (Pittsburgh Sleep Quality Index). The secondary outcomes are changes in sleep efficiency, sleep onset latency, wake after sleep onset, number of nocturnal awakenings (based on actigraph and sleep diary data), changes in insomnia severity (Insomnia Severity Index), well-being (WHO-5 Well-Being Index), personal recovery (INSPIRE-O), work ability (Work Ability Index), and consumption of sleep medication (sleep-diaries). Discussion: The study was initiated in 2022 and the inclusion period will continue until mid-2024. The results may have implications for the development and implementation of additional treatment options for patients with mental disorders and comorbid sleep problems. Trial registration: ClinicalTrials.gov. NCT05406414. Registered on June 6, 2022. [ABSTRACT FROM AUTHOR]

People with a diagnosis of schizophrenia often have poor sleep, even when their psychotic symptoms are relatively well managed. This includes insomnia, sleep apnoea, hypersomnia, and irregular or non-24 h sleep–wake timing. Improving sleep would better support recovery, yet few evidence-based sleep treatments are offered to this group. This paper presents a mixed methods feasibility and acceptability study of Light–Dark and Activity Rhythm Therapy (L-DART). L-DART is delivered by an occupational therapist over 12 weeks. It is highly personalisable to sleep phenotypes and circumstances. Ten participants with schizophrenia spectrum diagnoses and sleep problems received L-DART; their sleep problems and therapy goals were diverse. We measured recruitment, attrition, session attendance, and adverse effects, and qualitatively explored acceptability, engagement, component delivery, adherence, activity patterns, dynamic light exposure, self-reported sleep, wellbeing, and functioning. Recruitment was ahead of target, there was no attrition, and all participants received the minimum 'dose' of sessions. Acceptability assessed via qualitative reports and satisfaction ratings was good. Adherence to individual intervention components varied, despite high participant motivation. All made some potentially helpful behaviour changes. Positive sleep and functioning outcomes were reported qualitatively as well as in outcome measures. The findings above support testing the intervention in a larger randomised trial ISRCTN11998005. [ABSTRACT FROM AUTHOR]

One fifth of today's workforce is engaged in shift work and exposed to various mental and physical health risks including shift work disorder. Efficiently recovering from shift work through physical and mental interventions allows us to mitigate negative effects on health, enables a better work-life balance and enhances our overall wellbeing. The aim of this review is to provide a state-of-the-art overview of the available literature. The role of sleep timing and naps, light therapy and psychotherapy, diet and exercise in recovery from shift work is presented here. We further review the impact of shift schedules and social support on post-shift unwinding. [ABSTRACT FROM AUTHOR]

One fifth of today's workforce is engaged in shift work and exposed to various mental and physical health risks including shift work disorder. Efficiently recovering from shift work through physical and mental interventions allows us to mitigate negative effects on health, enables a better work-life balance and enhances our overall wellbeing. The aim of this review is to provide a state-of-the-art overview of the available literature. The role of sleep timing and naps, light therapy and psychotherapy, diet and exercise in recovery from shift work is presented here. We further review the impact of shift schedules and social support on post-shift unwinding.

Hypoxia‐ischemia (HI) of the brain not only impairs neurodevelopment but also causes pineal gland dysfunction, which leads to circadian rhythm disruption. However, the underlying mechanism of circadian rhythm disruption associated with HI‐induced pineal dysfunction remains unknown. The zinc finger protein repressor protein with a predicted molecular mass of 58 kDa (RP58) is involved in the development and differentiation of nerve cells. In this study, we established an HI model in neonatal rats to investigate the expression of RP58 and its role in pineal dysfunction and circadian rhythm disruption induced by HI. We demonstrated that RP58 was highly expressed in the pineal gland under normal conditions and significantly downregulated in the pineal gland and primary pinealocytes following HI. Knockdown of RP58 decreased the expression of enzymes in the melatonin (Mel) synthesis pathway (tryptophan hydroxylase 1 [TPH1], acetylserotonin O‐methyltransferase [ASMT], and arylalkylamine N‐acetyltransferase [AANAT]) and clock genes (circadian locomotor output cycles kaput [CLOCK] and brain and muscle ARNT‐like 1 [BMAL1]), and it also reduced the production of Mel, caused pineal cell injury, and disrupted circadian rhythms in vivo and in vitro. Similarly, HI reduced the expression of Mel synthesis enzymes (TPH1, ASMT, and AANAT) and clock genes (CLOCK and BMAL1), and caused pineal injury and circadian rhythm disruption, which were exacerbated by RP58 knockdown. The detrimental effect of RP58 knockdown on pineal dysfunction and circadian rhythm disruption was reversed by the addition of exogenous Mel. Furthermore, exogenous Mel reversed HI‐induced pineal dysfunction and circadian rhythm disruption, as reflected by improvements in Mel production, voluntary activity periods, and activity frequency, as well as a diminished decrease in the expression of Mel synthesis enzymes and clock genes. The present study suggests that RP58 is an endogenous source of protection against pineal dysfunction and circadian rhythm disruption after neonatal HI. [ABSTRACT FROM AUTHOR]

Light therapy is used to treat sleep and circadian rhythm disorders, yet there are limited studies on whether light therapy impacts electroencephalographic (EEG) activity during sleep. Therefore, we aimed to provide an overview of research studies that examined the effects of light therapy on sleep macro- and micro-architecture in populations with sleep and circadian rhythm disorders. We searched for randomized controlled trials that used light therapy and included EEG sleep measures using MEDLINE, PubMed, CINAHL, PsycINFO and Cochrane Central Register of Controlled Trials databases. Five articles met the inclusion criteria of patients with either insomnia or delayed sleep–wake phase disorder (DSWPD). These trials reported sleep macro-architecture outcomes using EEG or polysomnography. Three insomnia trials showed no effect of the timing or intensity of light therapy on total sleep time, wake after sleep onset, sleep efficiency and sleep stage duration compared to controls. Only one insomnia trial reported significantly higher sleep efficiency after evening light therapy (>4000 lx between 21:00–23:00 h) compared with afternoon light therapy (>4000 lx between 15:00–17:00 h). In the only DSWPD trial, six multiple sleep latency tests were conducted across the day (09:00 and 19:00 h) and bright light (2500 lx) significantly lengthened sleep latency in the morning (09:00 and 11:00 h) compared to control light (300 lx). None of the five trials reported any sleep micro-architecture measures. Overall, there was limited research about the effect of light therapy on EEG sleep measures, and studies were confined to patients with insomnia and DSWPD only. More research is needed to better understand whether lighting interventions in clinical populations affect sleep macro- and micro-architecture and objective sleep timing and quality.

[Display omitted] • The ameliorative effects of different teas on CRD induced metabolic dysfunction were compared. • Tea extracts upregulated FXR expression in the liver while downregulating their expression in the intestine. • Tea intervention improved CRD induced metabolic dysfunction by modulating the gut microbiota-bile acid -FXR axis. With the rapid development of society and changing lifestyles, people often encounter circadian rhythm disorder (CRD). Although tea active components have shown promise in improving CRD, a comprehensive comparison of different types of tea in improving CRD is still lacking, and the mechanism of regulating CRD-induced metabolic disorders remained unclear. This study selected three representative teas (Green tea, black tea, and dark tea) and compared the ameliorative effects of different teas on CRD-induced metabolic dysfunction. Furthermore, tea intervention improved the metabolic syndrome associated with CRD mainly through decreasing relative abundance of BSH-producing microbes, increasing conjugated bile acids (BAs) that act in an antagonistic manner on intestinal farnesoid X receptor (FXR), and promoting elimination of BAs via the feces. Our results shed light into the mechanisms behind the ameliorative effect of tea intervention on metabolic dysfunction caused by CRD, and suggest that the gut microbiota-bile acid-FXR axis may be potential therapies. [ABSTRACT FROM AUTHOR]

Light therapy is used to treat sleep and circadian rhythm disorders, yet there are limited studies on whether light therapy impacts electroencephalographic (EEG) activity during sleep. Therefore, we aimed to provide an overview of research studies that examined the effects of light therapy on sleep macro- and micro-architecture in populations with sleep and circadian rhythm disorders. We searched for randomized controlled trials that used light therapy and included EEG sleep measures using MEDLINE, PubMed, CINAHL, PsycINFO and Cochrane Central Register of Controlled Trials databases. Five articles met the inclusion criteria of patients with either insomnia or delayed sleep–wake phase disorder (DSWPD). These trials reported sleep macro-architecture outcomes using EEG or polysomnography. Three insomnia trials showed no effect of the timing or intensity of light therapy on total sleep time, wake after sleep onset, sleep efficiency and sleep stage duration compared to controls. Only one insomnia trial reported significantly higher sleep efficiency after evening light therapy (>4000 lx between 21:00–23:00 h) compared with afternoon light therapy (>4000 lx between 15:00–17:00 h). In the only DSWPD trial, six multiple sleep latency tests were conducted across the day (09:00 and 19:00 h) and bright light (2500 lx) significantly lengthened sleep latency in the morning (09:00 and 11:00 h) compared to control light (300 lx). None of the five trials reported any sleep micro-architecture measures. Overall, there was limited research about the effect of light therapy on EEG sleep measures, and studies were confined to patients with insomnia and DSWPD only. More research is needed to better understand whether lighting interventions in clinical populations affect sleep macro- and micro-architecture and objective sleep timing and quality. [ABSTRACT FROM AUTHOR]

Shift work sleep disorder is prevalent in night shift workers due to prolonged misalignment of the circadian rhythm. Night shift workers comprise a significant portion of the workforce and it is important to study the potential implications on their health. Studies have shown the association of metabolic syndrome (MetS) and the components, that is, obesity, dyslipidemia, hypertension, and insulin resistance, with shift workers. Nocturnal exposure to bright light can affect various physiological processes including melatonin secretion, which is a regulator in insulin synthesis. A systematic review was conducted to identify studies showing the association between shift work and MetS and/or its components, as well as to review the pathophysiology for further investigations. This review follows the guidelines as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist 2009. One thousand nine hundred ten records were identified from the PubMed database using both keywords and medical subject headings terms. After applying the inclusion/exclusion and eligibility criteria, 18 observational studies were included in the qualitative synthesis. Quality appraisal was conducted by two investigators independently using the Newcastle/Ottawa Scale, and 11 articles were finalized for the review after scoring 60% and above. Each study measured the different components of MetS and/or the presence of MetS. Statistically significant results were reported for the association between shift work and MetS, shift work and obesity, shift work and dyslipidemia, shift work and hypertension, and shift work and insulin resistance. This review identifies a need to emphasize treatment plans for shift workers to manage not only sleep disorders but other chronic diseases such as MetS, obesity, hypertension, dyslipidemia, and insulin resistance. [ABSTRACT FROM AUTHOR]

Flight safety reports from different sources indicate that the proportion of accidents caused by flight fatigue accounts for 6-11% of all types of flight accidents. Current regulations in the civil aviation industry across the world generally emphasize the length of working hours rather than the influences of circadian rhythm disorders. Based on an analysis of the flight mission data of 567 pilots in 2019, which highlighted the associations between circadian rhythm disorders and flight fatigue, we have proposed a new algorithm to reflect pilots’ fatigue status to include five main indicators: actual working hours, circadian rhythm disorders, work rhythm disorder, altitude flight hours and flight crew composition. The results assessed by the new algorithm reported that about 70% of the airline pilots studied were under the threat of a high risk of fatigue in 2019. Subsequently, this research suggests the use of two algorithms to optimize pilot scheduling systems, and findings show that the percentage of pilots with a high level of fatigue can be largely reduced.

Parkinson's disease (PD) is an alpha-synucleinopathy that leads to prominent motor symptoms including tremor, bradykinesia, and postural instability. Nonmotor symptoms including autonomic, neurocognitive, psychiatric symptoms, and sleep disturbances are also seen frequently in PD. The impact of PD on sleep is related to motor and nonmotor symptoms, in addition to the disruption of the pathways regulating sleep by central nervous system pathology. Rapid eye movement sleep behavior disorder is a parasomnia that can lead to self-injury and/or injury to partners at night. Restless legs syndrome is a subjective sensation of discomfort and urge to move the legs prior to falling asleep and can lead to insomnia and reduced sleep quality. Excessive daytime sleepiness is common in PD and exerts a negative impact on quality of life in addition to increasing the risk of falls. Obstructive sleep apnea is a breathing disorder during sleep that can cause frequent awakenings and excessive daytime sleepiness. Circadian rhythm dysfunction can lead to an advanced or delayed onset of sleep in patients and create disruption of normal sleep and wake times. All of these disorders are common in PD and can significantly reduce sleep quantity, sleep quality, or quality of life for patients and caretakers. Treatment approaches for each of these disorders are distinct and should be individualized to the patient. We review the literature regarding these common sleep issues encountered in PD and their treatment options. [ABSTRACT FROM AUTHOR]

Jet lag is commonly experienced when travelers cross multiple time zones, leaving the wake–sleep cycle and intrinsic biological "clocks" out of synchrony with the current environment. The effect of jet lag on intrinsic cortical function remains unclear. Twenty‐two healthy individuals experiencing west‐to‐east jet lag flight were recruited. Brain structural and functional magnetic resonance studies, as well as psychological and neurohormonal tests, were carried out when participants returned from travel over six time zones and 50 days later when their jet lag symptoms had resolved. During jet lag, the functional brain network exhibited a small‐world topology that was shifted toward regularity. Alterations during jet lag relative to recovery included decreased basal ganglia‐thalamocortical network connections and increased functional connectivity between the medial temporal lobe subsystem and medial visual cortex. The lower melatonin and higher thyroid hormone levels during jet lag showed the same trend as brain activity in the right lingual gyrus. Although there was no significant difference between cortisol measurements during and after jet lag, cortisol levels were associated with temporal lobe activity in the jet lag condition. Brain and neuroendocrine changes during jet lag were related to jet lag symptoms. Further prospective studies are needed to explore the time course over which jet lag acts on the human brain. [ABSTRACT FROM AUTHOR]

Background: In a previous study developed by our group, we identified a phase inversion in 6-sulfatoxymelatonin - melatonin metabolite in urine - daily profile in Fabry's disease patients. Since melatonin is an endogenous marker, it could also be accompanied by behavioral changes in sleep-wake cycle, which impairs the overall patient's life quality.Objective: In this study, we evaluated sleep-wake cycle in Fabry disease patients. We hypothesized that patients would have increased daytime naps, given our previous results for urinary 6-sulfatoxymelatonin.Patients/methods: This was a cross-sectional and case-control study, performed between October 2016 and May 2017. Volunteers recorded activity and rest rhythm by actigraphy and answered Pittsburgh Sleep Quality Index (PSQI). From actigraphy data, we calculated sleep parameters: sleep latency, wake after sleep onset, sleep (WASO) efficiency, awakenings index (PSQI), and the amount and duration of daytime naps. We included 16 Fabry disease patients with biochemical and molecular diagnosis and 10 control individuals matched by age and gender.Results: We did not observe significant differences for any of the parameters analyzed (p > 0.05). However, evaluating the magnitude of the effect, we found that patients dozed, on average, about 42 min longer (d = 0.9 - large effect size) than control group.Conclusions: This is a preliminary study, a proof-of-concept, and our results indicate that changes in melatonin secretion phase may have behavioral consequences in sleep-wake cycle, with longer duration of daytime naps. [ABSTRACT FROM AUTHOR]

Abstract Background Sleep problems are very common in people with schizophrenia spectrum disorders, and impact negatively on functioning and wellbeing. Research regarding interventions to improve sleep in this population has been lacking. Little is known regarding these patient’s perspectives on sleep problems and their treatment, providing very little foundation on which to develop acceptable and patient-centred treatments. Methods This study aims to explore perspectives and priorities of participants with schizophrenia spectrum disorders regarding sleep and sleep disturbance, and their perspectives on existing treatments. An Interpretive Phenomenological Analysis (IPA) study was conducted; data were gathered through in depth interviews with 15 people with schizophrenia spectrum disorders and varying degrees of self-reported sleep disturbance, each case was analysed individually before cross-case comparisons were made. Results Sleep maintenance and sleep quality were universally valued. Changes to sleep were interpreted as part of a perceived loss of normality relating to diagnosis. Participants differed in the extent of any hopes that sleep would improve. Sleep disturbances were linked to a reduced ability or opportunity to participate in valued activities, and were entangled with self-image due to a wish to be perceived as alert and in control. During difficult times, sleep could be seen as an escape. Concerns were expressed regarding the negative effects of using hypnotics or anti-psychotics to aid sleep, although typically antipsychotics were deemed more acceptable than hypnotics. Concerns regarding barriers to adherence and effectiveness of self-help approaches were common. Non-pharmacological interventions were noted to require a personalised whole-lifestyle approach. Conclusions This is the first study to explore sleep perspectives in participants with established schizophrenia spectrum disorders, recruited from a population receiving usual care. Findings re-enforce the importance of considering sleep within recovery focused practice. In developing and adapting interventions routine-based approaches should be considered. Approaches should attempt to make gradual changes more easily perceptible, should support motivation for behaviour change, and should consider the impact of regular psychotropic medications.

The interplay between genetic and environmental risk factors contributes to the pathogenesis of metabolic disease. Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age. Circadian rhythm disruption is an important risk factor for PCOS. In this study, we evaluated the effect of circadian disorder on reproduction as well as metabolism, and determined its influence on gut microbiota in a rat model. Female Sprague Dawley (SD) rats were kept under continuous light exposure (12-h:12-h light/light cycle, L/L group) or a control cycle (12-h:12-h light/dark cycle, L/D group) for four consecutive weeks. Manifestations in endocrine hormones and metabolism were detected and gut microbiota were analyzed with the 16s rRNA gene sequencing technique. To our knowledge, this is the first study to report PCOS-like reproductive manifestation, such as anti-Müllerian hormone (AMH) elevation induced by continuous light exposure. Moreover, continuous light resulted in abnormal glucose metabolism and gut microbial community variations, including enrichment of the microbial genus of Parasutterella and reduced abundance of genus Corynebacterium, genus Odoribacter, and genus Acinetobacter. Increased Parasutterella abundance was positively correlated with serum testosterone level. A PICRUSt analysis revealed that reproductive and metabolic-related genes were enriched in rats of L/D group. In conclusion, the present study demonstrates that continuous light exposure, an important environmental factor, contributes to the occurrence and developmental progress of PCOS and changes in microbial component and structure. Continuous light exposure is one of vital causes of PCOS, which is closely related to microbial structure and functions.

The interplay between genetic and environmental risk factors contributes to the pathogenesis of metabolic disease. Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age. Circadian rhythm disruption is an important risk factor for PCOS. In this study, we evaluated the effect of circadian disorder on reproduction as well as metabolism, and determined its influence on gut microbiota in a rat model. Female Sprague Dawley (SD) rats were kept under continuous light exposure (12-h:12-h light/light cycle, L/L group) or a control cycle (12-h:12-h light/dark cycle, L/D group) for four consecutive weeks. Manifestations in endocrine hormones and metabolism were detected and gut microbiota were analyzed with the 16s rRNA gene sequencing technique. To our knowledge, this is the first study to report PCOS-like reproductive manifestation, such as anti-Müllerian hormone (AMH) elevation induced by continuous light exposure. Moreover, continuous light resulted in abnormal glucose metabolism and gut microbial community variations, including enrichment of the microbial genus of Parasutterella and reduced abundance of genus Corynebacterium , genus Odoribacter , and genus Acinetobacter. Increased Parasutterella abundance was positively correlated with serum testosterone level. A PICRUSt analysis revealed that reproductive and metabolic-related genes were enriched in rats of L/D group. In conclusion, the present study demonstrates that continuous light exposure, an important environmental factor, contributes to the occurrence and developmental progress of PCOS and changes in microbial component and structure. Continuous light exposure is one of vital causes of PCOS, which is closely related to microbial structure and functions. [ABSTRACT FROM AUTHOR]

Background: Sleep disorders, along with extreme difficulty in awakening, are one of the main causes of school refusal. The accumulation of chronic sleep deprivation accompanied by a late‐night lifestyle is considered the basic inciting factor. Methods: From 2007, we initiated a sleep education program (Min‐Iku) in Fukui, Japan, with the aim of improving pupil lifestyle and preventing future school refusal. All grade 1‐6 Miyake‐primary school (M‐PS) pupils participated in this program and gave their informed consent. The Min‐Iku included (i) implementation of a "daily life rhythm survey" by recording the sleep–wake rhythm in a table for 14 days; (ii) evaluation of the sleep table according to the classifications A–D; (iii) interviews of stage D children and their guardians; (iv) lectures on the importance of daily life rhythms for parents and teachers; and (v) 45 min classwork for all participating pupils. Results: In 2007, 10% of M‐PS graduates developed school refusal behavior after entering Kaminaka junior high school (K‐JHS). The incidence of school refusal, however, decreased each year after the implementation of the Min‐Iku program and finally reached 0 by 2012. The sleep onset time of pupils improved each year, with the most common sleep time reaching 9:30 p.m. on both weekdays and holidays. With an earlier sleep time, the night‐time sleep duration was significantly extended (P < 0.001 vs 2007 data). Conclusion: The Min‐Iku program for primary school pupils successfully achieved a more routine night‐time sleep pattern and a regular life rhythm, which prevented school refusal during the subsequent JHS years. [ABSTRACT FROM AUTHOR]

The Pittsburgh Sleep Quality Index (PSQI) is a measure of self-reported sleep quality and sleep disturbance. Though the PSQI is widely used, it is unclear if it adequately assesses self-reported sleep disturbance in people with schizophrenia spectrum disorders. We used mixed methods to examine the relationship between scores on the PSQI and qualitative self-report during in-depth interview in a group of participants diagnosed with schizophrenia spectrum disorders (N = 15). Although the PSQI appears to accurately capture issues related to sleep initiation, average duration, and interruption by physical complaints, it did not adequately assess other salient issues including irregularity in sleep duration and timing, shallow unrefreshing sleep, prolonged sleep inertia, hypersomnia, and sleep interrupted by mental or psychological complaints. In interview by contrast these types of problems were readily reported and described as important by participants. Our findings suggest that using the PSQI summary score as a measurement of general sleep disturbance in this population may be misleading, as this failed to capture some of the types of sleep problems that are particularly common in this group. [ABSTRACT FROM AUTHOR]

Marilou DP Tromp,1 Anouk AMT Donners,1 Johan Garssen,1,2 Joris C Verster1,31Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; 2Nutricia Research, Utrecht, the Netherlands; 3Center for Human Psychopharmacology, Swinburne University, Melbourne, VIC, AustraliaObjective: To investigate the relationship between eating disorders, body mass index (BMI), sleep disorders, and daytime functioning.Design: Survey.Setting: The Netherlands.Participants: N=574 Dutch young adults (18–35 years old).Measurements: Participants completed a survey on eating and sleep habits including the Eating Disorder Screen for Primary care (ESP) and SLEEP-50 questionnaire subscales for sleep apnea, insomnia, circadian rhythm disorder (CRD), and daytime functioning. SLEEP-50 outcomes of participants who screened negative (≤2) and positive (>2) on the ESP were compared. In addition, SLEEP-50 scores of groups of participants with different ESP scores (0–4) and different BMI groups (ie, underweight, healthy weight, overweight, and obese) were compared using nonparametric statistics.Results: Almost 12% (n=67) of participants screened positive for having an eating disorder. Relative to participants without eating disorders, participants who screened positive for eating disorders reported significantly higher scores on sleep apnea (3.7 versus 2.9, P=0.012), insomnia (7.7 versus 5.5, P

The non-24-hour sleep-wake disorder (N24SWD) is a rare condition, sometimes associated with blindness or with suprachiasmatic nuclei lesions, resulting in a free-running rhythm or hypernycthemeral syndrome. Synchronizers, such as light, when light perception remains, melatonin, food intakes, physical activity, social interactions, and temperature, play a key role in the treatment of N24SWD. In this report, we describe a case illustrating the impact of outdoor temperature in a 34-year-old man with N24SWD effectively treated through a combination of chronotherapy interventions. During 3 consecutive heat waves, he experienced a recurrence of his natural 25.5-hour free-running rhythm, with a consistent bedtime phase delay caused by temperature, resulting in the discontinuation of chronotherapy. After these heat waves, he was able again to resynchronize his rhythms with the combination of chronotherapeutics. This case report highlights that patients with N24SWD may be particularly at risk of relapse during heat waves, with direct implications for monitoring and reinforcing chronotherapies., Citation: Garrivet J, d'Ortho M-P, Frija-Masson J, et al. "Too much heat for my non-24-hour sleep-wake disorder!" A case report. J Clin Sleep Med . 2024;20(2):329-333., (© 2024 American Academy of Sleep Medicine.)

Background: Sleep problems are very common in people with schizophrenia spectrum disorders, and impact negatively on functioning and wellbeing. Research regarding interventions to improve sleep in this population has been lacking. Little is known regarding these patient's perspectives on sleep problems and their treatment, providing very little foundation on which to develop acceptable and patient-centred treatments. Methods: This study aims to explore perspectives and priorities of participants with schizophrenia spectrum disorders regarding sleep and sleep disturbance, and their perspectives on existing treatments. An Interpretive Phenomenological Analysis (IPA) study was conducted; data were gathered through in depth interviews with 15 people with schizophrenia spectrum disorders and varying degrees of self-reported sleep disturbance, each case was analysed individually before cross-case comparisons were made. Results: Sleep maintenance and sleep quality were universally valued. Changes to sleep were interpreted as part of a perceived loss of normality relating to diagnosis. Participants differed in the extent of any hopes that sleep would improve. Sleep disturbances were linked to a reduced ability or opportunity to participate in valued activities, and were entangled with self-image due to a wish to be perceived as alert and in control. During difficult times, sleep could be seen as an escape. Concerns were expressed regarding the negative effects of using hypnotics or anti-psychotics to aid sleep, although typically antipsychotics were deemed more acceptable than hypnotics. Concerns regarding barriers to adherence and effectiveness of self-help approaches were common. Non-pharmacological interventions were noted to require a personalised whole-lifestyle approach. Conclusions: This is the first study to explore sleep perspectives in participants with established schizophrenia spectrum disorders, recruited from a population receiving usual care. Findings re-enforce the importance of considering sleep within recovery focused practice. In developing and adapting interventions routine-based approaches should be considered. Approaches should attempt to make gradual changes more easily perceptible, should support motivation for behaviour change, and should consider the impact of regular psychotropic medications. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDs) affect 15% of the world's population and are becoming an increasingly common cause of morbidity and mortality worldwide. Circadian rhythm disorders (CRDs) have been reported to be involved in the pathogenic regulation of various neurologic diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis. Proteomic technology is helpful to explore treatment targets for CRDs in patients with NDs. Here, we review the key differentially expressed (DE) proteins identified in previous proteomic studies investigating NDs, CRDs and associated models and the related pathways identified by enrichment analysis. Furthermore, we summarize the advantages and disadvantages of the above studies and propose new proteomic technologies for the precise study of circadian disorder-mediated regulation of ND pathology. This review provides a theoretical and technical reference for the precise study of circadian disorder-mediated regulation of ND pathology. [ABSTRACT FROM AUTHOR]

Light is the major environmental time cue that synchronizes the endogenous central circadian pacemaker, located in the suprachiasmatic nuclei of the hypothalamus, and is detected exclusively by the eyes primarily via specialized non-rod, non-cone ganglion cell photoreceptors. Consequently, most blind people with no perception of light (NPL) have either nonentrained or abnormally phased circadian rhythms due to this inability to detect light. Conversely, most visually impaired participants with some degree of light perception (LP) exhibit normal entrainment, emphasizing the functional separation of visual and “nonvisual” photoreception. The aims of the study were to identify the prevalence of circadian disorders in blind women, with the further aim of examining how eye disease may relate to the type of circadian disorder. Participants (n = 127, age 50.8 ± 13.4 years) completed an 8-week field study including daily sleep diaries and sequential 4 to 8 hourly urine collections over 48 h on 2 to 3 occasions separated by at least 2 weeks. Circadian type was determined from the timing and time course of the melatonin rhythm measured by cosinor-derived urinary 6-sulfatoxymelatonin rhythm peak. Of the participants with NPL (n = 41), the majority were abnormally phased (24%) or nonentrained (39%), with 37% classified as normally entrained. Of the participants with LP (n = 86), the majority were normally entrained (69%). Eighteen LP participants (21%) were abnormally phased (8 advanced, 10 delayed). Nine LP participants (10%) were nonentrained. The eye conditions most associated with abnormal phase and/or nonentrained circadian rhythms were bilateral enucleation (67%) and retinopathy of prematurity (57%). By contrast, 84% of participants with retinitis pigmentosa and 83% of those with age-related macular degeneration were normally entrained. These findings suggest that the etiology of blindness in addition to LP status is related to an individual’s ability to process the circadian light signal. [ABSTRACT FROM PUBLISHER]

Sleep disorders commonly afflict infants, children, and adolescents and have a significant adverse impact on them and their families, sometimes to a severe degree. They can cause immediate stress and suffering and long-term loss of opportunities and potential. Many of these disorders can be well managed by the psychologist and often one is required, either as the sole provider or as an integral part of a team. Sleep disorders have a bidirectional interplay with mental health disorders. The patient may therefore present initially to the psychologist, primary care provider, or the sleep medicine specialist., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Patients with cerebral degenerative conditions commonly suffer from a variety of sleep disorders, including sleep-disordered breathing, insomnia, parasomnias (REM sleep behavior disorder), circadian rhythm disturbances, and restless legs syndrome. When these sleep disorders go unrecognized and untreated, they can lead to decreased quality of life and worsening neurological symptoms related to the underlying condition. Appropriate management initially requires taking a careful history from the patient and bed partner regarding their sleep. In addition, polysomnography may be required to aid in the diagnosis of sleep-disordered breathing or parasomnias. Occasionally, adjusting the dosages of sedating or sleep disrupting medications and improving sleep hygiene may improve sleep complaints. However, in most cases restoring quality nighttime sleep requires specific therapeutic intervention. In patients that suffer from sleep apnea, this usually means treatment with continuous positive airway pressure (CPAP), positional therapy, dental appliances, upper airway surgery, or weight loss. Pharmacological treatment of insomnia in patients with cerebral degenerative conditions can be difficult due to side effects (worsening balance, cognition) and lack of data in this patient population. Behavioral strategies such as cognitive-behavioral therapy have been effective and are considered safer than hypnotic therapy, but can be limited due to access to trained providers (distance and number of providers) and limited cognitive functioning of the patient. Parasomnias, namely REM sleep behavior disorder, are managed by looking for any underlying cause of arousals (sleep apnea, periodic leg movements of sleep), implementing safety precautions, and pharmacologically with either benzodiazepines or melatonin. Restless legs syndrome may improve with iron replacement or dopamine agonist therapy, as it does in other patient populations. Light therapy may be beneficial in patients suffering from circadian rhythm disorders such as advanced sleep phase syndrome. [ABSTRACT FROM AUTHOR]

Sleep disorders are common in the general population and even more so in clinical practice, yet are relatively poorly understood by doctors and other health care practitioners. These British Association for Psychopharmacology guidelines are designed to address this problem by providing an accessible up-to-date and evidence-based outline of the major issues, especially those relating to reliable diagnosis and appropriate treatment. A consensus meeting was held in London in May 2009. Those invited to attend included BAP members, representative clinicians with a strong interest in sleep disorders and recognized experts and advocates in the field, including a representative from mainland Europe and the USA. Presenters were asked to provide a review of the literature and identification of the standard of evidence in their area, with an emphasis on meta-analyses, systematic reviews and randomized controlled trials where available, plus updates on current clinical practice. Each presentation was followed by discussion, aimed to reach consensus where the evidence and/or clinical experience was considered adequate or otherwise to flag the area as a direction for future research. A draft of the proceedings was then circulated to all participants for comment. Key subsequent publications were added by the writer and speakers at draft stage. All comments were incorporated as far as possible in the final document, which represents the views of all participants although the authors take final responsibility for the document. [ABSTRACT FROM PUBLISHER]

Melatonin secretion is synchronized to the sleep/wake cycle and has been suggested to have somnogenic properties. Sleep/wake cycle disruption and alterations in the secretary pattern of melatonin is present in various psychiatric disorders. The objective of this study was to investigate the sleep architecture and the presence of depression in individuals with low endogenous melatonin levels. The study included 16 participants (mean age 30.3 ± 14.9 years). The first night of testing included psychiatric evaluation followed by melatonin secretion profile evaluation by Dim Light Melatonin Onset test and then standard montage polysomnographic testing. On the second night, only polysomnographic testing was carried out with an imposed sleep period of 8 h. Low endogenous melatonin secretors (LEMS) showed no discernible peaks in melatonin secretion compared to normal secretors (controls). LEMS demonstrated significant alterations in rapid eye movement sleep but not in non-rapid eye movement sleep along with poor sleep initiation and quality compared to controls. 55.6% of the low melatonin secretors group presented with subsyndromal depression. Melatonin has significant bearing on sleep architecture and a lack of melatonin may desynchronize endogenous rhythms allowing subsyndromal depression to manifest. [ABSTRACT FROM AUTHOR]

Sleep disturbances are a very sensitive indicator, which allows identifying various psychic illnesses, especially depression. Irrelevant of the very nature of sleep disturbances, their presence can tell us about the onset of depression or its ending. The mechanism of sleep disturbances seems to be tightly bound with the physiology of depression. Besides physiological, neuroendocrine and behavioural parameters, which are altered in depression, sleep disturbances play a more exposed role in the recent years. This has been brought about by a better identification of daily rhythm disorders in major depressive disorder (MDD), bipolar disorder (BD) or seasonal affective disorder (SAD) and the discovery of a correlation between lowered mood and changes in the rhythm and level of melatonine secretion. Also, the discovery of the substance which is supposedly correcting the disordered circadian rhythm (agomelatine), means a step forward in the search for an effective treatment of depression. It is worthy to look closer into its regulatory effect on the disordered circadian rhythm, which is not only to give an antidepressive effect, but in a visible improvement of sleep architecture and functioning during the day. [ABSTRACT FROM AUTHOR]

Abstract: Background: Delayed Sleep Phase Syndrome (DSPS) arises from biological clock desynchrony and accounts for 10% of chronic insomnia patients. Currently DSPS is diagnosed based on sleep/wake cycle disruptions rather than examining the underlying biological clock alterations. The objective of the study was to determine the sensitivity and specificity of the Dim Light Melatonin Onset (DLMO) Test in diagnosing DSPS in a clinical setting. Methods: Fifty-six patients (mean age 28 years) symptomatic of DSPS participated in the study. Following an initial assessment of DSPS using sleep diaries, participants underwent two consecutive nights of polysomnography (PSG), with an imposed sleep period on the second night to demonstrate the delay in the timing of habitual sleep period and to thereby confirm DSPS. Circadian phase delays were also measured using melatonin secretion profiles, and the efficacy of diagnosing DSPS using DLMO was compared to using sleep diaries and PSG. Melatonin secretion was assayed for each individual by ELISA using saliva samples. Results: Main outcome measures included the time of melatonin secretion onset, clinical sensitivity and specificity of the DLMO test. The time of melatonin secretion onset was significantly delayed in DSPS patients. Clinical sensitivity and specificity of the DLMO test in diagnosing DSPS were 90.3% and 84.0%, respectively. Conclusions: The DLMO test is an accurate tool for differentiating between sleep disorder patients with or without underlying circadian rhythm disruption. It is effective for phase typing DSPS patients in a clinical setting. [Copyright &y& Elsevier]