Orexin Receptor Antagonism: Normalizing Sleep Architecture in Old Age and Disease.

Sleep is essential for human well-being, yet the quality and quantity of sleep reduce as age advances. Older persons (>65 years old) are more at risk of disorders accompanied and/or exacerbated by poor sleep. Furthermore, evidence supports a bidirectional relationship between disrupted sleep and Alzheimer's disease (AD) or related dementias. Orexin/hypocretin neuropeptides stabilize wakefulness, and several orexin receptor antagonists (ORAs) are approved for the treatment of insomnia in adults. Dysregulation of the orexin system occurs in aging and AD, positioning ORAs as advantageous for these populations. Indeed, several clinical studies indicate that ORAs are efficacious hypnotics in older persons and dementia patients and, as in adults, are generally well tolerated. ORAs are likely to be more effective when administered early in sleep/wake dysregulation to reestablish good sleep/wake-related behaviors and reduce the accumulation of dementia-associated proteinopathic substrates. Improving sleep in aging and dementia represents a tremendous opportunity to benefit patients, caregivers, and health systems.

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

The 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.

Fractal biomarker of activity in patients with bipolar disorder.

BACKGROUND: The output of many healthy physiological systems displays fractal fluctuations with self-similar temporal structures. Altered fractal patterns are associated with pathological conditions. There is evidence that patients with bipolar disorder have altered daily behaviors. METHODS: To test whether fractal patterns in motor activity are altered in patients with bipolar disorder, we analyzed 2-week actigraphy data collected from 106 patients with bipolar disorder type I in a euthymic state, 73 unaffected siblings of patients, and 76 controls. To examine the link between fractal patterns and symptoms, we analyzed 180-day actigraphy and mood symptom data that were simultaneously collected from 14 patients. RESULTS: Compared to controls, patients showed excessive regularity in motor activity fluctuations at small time scales (<1.5 h) as quantified by a larger scaling exponent (α1 > 1), indicating a more rigid motor control system. α1 values of siblings were between those of patients and controls. Further examinations revealed that the group differences in α1 were only significant in females. Sex also affected the group differences in fractal patterns at larger time scales (>2 h) as quantified by scaling exponent α2. Specifically, female patients and siblings had a smaller α2 compared to female controls, indicating more random activity fluctuations; while male patients had a larger α2 compared to male controls. Interestingly, a higher weekly depression score was associated with a lower α1 in the subsequent week. CONCLUSIONS: Our results show sex- and scale-dependent alterations in fractal activity regulation in patients with bipolar disorder. The mechanisms underlying the alterations are yet to be determined.

Prevalence and associated factors of circadian rhythm sleep-wake disorders and insomnia among visually impaired Japanese individuals.

BACKGROUND: Although earlier studies have demonstrated that circadian rhythm sleep-wake disorders (CRSWD) are more prevalent in visually impaired individuals, the actual prevalence of CRSWD and insomnia among the visually impaired Japanese population remains unclear. The aim of this cross-sectional, telephone-based study was to estimate the prevalence of CRSWD and insomnia, and explore factors associated with CRSWD and insomnia among visually impaired Japanese individuals. METHODS: A nationwide telephone survey was conducted among visually-impaired individuals through local branches of the Japan Federation of the Blind. In total, 157 visually impaired individuals were eligible for this study. Demographic information and information about visual impairments, lifestyle, and sleep patterns were assessed using questionnaires and subsequent telephone interviews. CRSWD and insomnia were defined according to the International Classification of Sleep Disorders-Third Edition criteria. RESULTS: The prevalence of CRSWD in visually impaired individuals was 33.1%. Among those with CRSWD, a non-24-h/irregular sleep-wake rhythm type was the most frequently observed (26.8%), followed by an advanced sleep-wake phase type and a delayed sleep-wake phase type (3.8 and 2.5%, respectively). Furthermore, 28.7% of the visually impaired individuals were found to have insomnia. In the visually impaired individuals, the absence of light perception, unemployment, living alone, and use of hypnotics were significantly associated with CRSWD, whereas only the use of hypnotics was extracted as a marginally associated factor of insomnia. CONCLUSIONS: CRSWD and insomnia were highly prevalent in visually impaired Japanese individuals. The presence of CRSWD among the visually impaired individuals was associated with a lack of light perception and/or social zeitgebers.

Inactograms and objective sleep measures as means to capture subjective sleep problems in patients with a bipolar disorder.

BACKGROUND: Sleep problems are common in bipolar disorders (BDs). To objectively characterize these problems in BDs, further methodological development is needed to capture subjective insomnia. AIM: To test psychometric properties of the Athens Insomnia Scale (AIS), and associations with actigraphy-derived measures, applying modifications in actigraphy data processing to capture features of perturbed sleep in patients with a BD. METHODS: Seventy-four patients completed the AIS and the Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR-16). Locomotor activity was continuously recorded by wrist actigraphy for ≥10 consecutive days. We computed the sleep onset/offset, the center of daily inactivity (CenDI), as a proxy for chronotype, and the degree of consolidation of daily inactivity (ConDI), as a proxy for sleep-wake rhythm strength. RESULTS: AIS showed good psychometric properties (Cronbach's alpha = 0.84; test-retest correlation = 0.84, P<.001). Subjective sleep problems correlated moderately with a later sleep phase (CenDI with AIS rho = 0.34, P = .003), lower consolidation (ConDI with AIS rho = -0.22, P = .05; with QIDS-SR-16 rho = -0.27, P = .019), later timing of sleep offset (with AIS rho = 0.49, P = ≤.001, with QIDS-SR-16 rho = 0.36, P = .002), and longer total sleep (with AIS rho = 0.29, P = .012, with QIDS-SR-16 rho = 0.41, P = ≤.001). While AIS was psychometrically more solid, correlations with objective sleep were more consistent across time for QIDS-SR-16. CONCLUSIONS: AIS and QIDS-SR-16 are suitable for clinical screening of sleep problems among patients with a BD. Subjective insomnia associated with objective measures. For clinical and research purposes, actigraphy and data visualization on inactograms are useful for accurate longitudinal characterization of sleep patterns.

Early chronotype with advanced activity rhythms and dim light melatonin onset in a rural population.

Studying communities at different stages of urbanisation and industrialisation can teach us how timing and intensity of light affect the circadian clock under real-life conditions. We have previously described a strong tendency towards morningness in the Baependi Heart Study, located in a small rural town in Brazil. Here, we tested the hypothesis that this morningness tendency is associated with early circadian phase based on objective measurements (as determined by dim light melatonin onset, DLMO, and activity) and light exposure. We also analysed how well the previously collected chronotype questionnaire data were able to predict these DLMO values. The average DLMO observed in 73 participants (40 female) was 20:03 ± 01:21, SD, with an earlier average onset in men (19:38 ± 01:16) than in women (20:24 ± 01:21; P ≤ .01). However, men presented larger phase angle between DLMO and sleep onset time as measured by actigraphy (4.11 hours vs 3.16 hours; P ≤ .01). Correlational analysis indicated associations between light exposure, activity rhythms and DLMO, such that early DLMO was observed in participants with higher exposure to light, higher activity and earlier light exposure. The strongest significant predictor of DLMO was morningness-eveningness questionnaire (MEQ) (beta=-0.35, P ≤ .05), followed by age (beta = -0.47, P ≤ .01). Sex, light exposure and variables derived from the Munich chronotype questionnaire were not significant predictors. Our observations demonstrate that both early sleep patterns and earlier circadian phase have been retained in this small rural town in spite of availability of electrification, in contrast to metropolitan postindustrial areas.

Food addiction and symptoms of depression among inhabitants of the European North of Russia: Associations with sleep characteristics and photoperiod.

The purpose of this investigation was to study the sleep-wake rhythm characteristics of young persons with food addiction (FA) and symptoms of depression. A total of 2,360 young persons living in northern European Russia were included in the study. The average age of the respondents (± standard deviation [SD]) was 17.9 [4.6] years (66.6% female). Each participant provided personal data and filled in three questionnaires: the Munich Chronotype Questionnaire, the Zung Self-Rating Depression Scale, and the Yale Food Addiction Scale. FA was detected in 8.9% of respondents, and moderate-to-severe symptoms of depression were detected in 16.7% of respondents. FA and depressive symptoms were more often detected in females. Age and body mass index were shown to be significantly associated with FA. There were positive associations between the time of sunrise and FA and depressive symptoms. Persons who had symptoms of depression also tended to have a later chronotype, lower sleep efficiency, later sleep onset, higher sleep inertia, and greater sleep latency on school days. A positive relationship between FA and the time of sleep onset on school days was also revealed. Thus, the results indicate that prolonged wakefulness in the evening after sunset was associated with FA.

Circadian Rhythm Disturbances in the Blind.

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

Moderating effects of depressive symptoms on the relationship between problematic use of the Internet and sleep problems in Korean adolescents.

BACKGROUND: Adolescence is a period of marked sleep pattern changes and sleep problems, which may result from both endogenous and exogenous factors. Among the various factors affecting adolescent sleep, depression and problematic Internet use (PIU) have received considerable attention. We examined if there is a different PIU effect on sleep between depressed group and non-depressed groups. METHODS: Data for a total of 766 students' between 7th and 11th grades were analyzed. We assessed various variables related sleep to problems and depression and compared those variables between an adolescent group with problematic Internet use (PIUG) and an adolescent group with normal Internet use (NIUG). RESULTS: One hundred fifty two participants were classified as PIUG, and 614 were classified as NIUG. Compared with the NIUG, the members of the PIUG were more prone to insomnia, excessive daytime sleepiness and sleep-wake behavior problems. The PIUG also tended to include more evening types than the NIUG. Interestingly, the effect of Internet use problems on sleep problems appeared to be different according to the presence or absence of the moderating effect of depression. When we considered the moderating effect of depression, the effect of Internet use problems on sleep-wake behavior problems, insomnia and excessive daytime sleepiness increased with increasing Young's Internet Addiction Scale (IAS) scores in the non-depressed group. However, in the depressed group, the effects of Internet use problems on sleep-wake behavior problems and insomnia did not change with increasing Internet use problems, and the effect of Internet use problems on excessive daytime sleepiness was relatively decreased with increasing Internet use problems in the depressed group. CONCLUSIONS: This study demonstrated that the effect of PIU on sleep presented differently between the depressed and non-depressed groups. PIU is associated with poorer sleep in non-depressed adolescents but not in depressed adolescents. This finding might be observed because PIU may be the biggest contributor to sleep problems in the problematic Internet user without depression, but in the problematic Internet user with depression, depression might be a more important contributor to sleep problems; thus, the influence of PIU on sleep effect might be diluted.

Effects of maternity yoga on the autonomic nervous system during pregnancy.

AIM: To elucidate the changes in the daily variation seen in the autonomic nervous system during pregnancy brought about by maternity yoga and to evaluate how maternal yoga affects stress and sleep. METHODS: A prospective, longitudinal study was conducted between January 2013 and December 2014. Pregnant women who were attending maternity yoga classes at Palmore Hospital between 20 and 23 weeks' gestation were enrolled as the yoga group, and a matched control group was also enrolled. Study participants completed questionnaires, including a perceived stress scale and sleep logs, during their second and third trimesters. Heart rate variability and salivary α-amylase levels were evaluated as stress indices at 20-23 weeks' gestation, 28-31 weeks' gestation and 36-40 weeks' gestation. RESULTS: A total of 38 women were in the yoga group, with 53 in the control group. At 28-31 weeks' gestation, heart rate variability during night and late-night periods was significantly higher in the yoga group than in the control group. At 36-40 weeks' gestation, variability between the morning, afternoon and late night was significantly higher in the yoga group. Salivary α-amylase levels decreased significantly immediately after practicing yoga during all evaluation periods in the yoga group. Night-time sleep duration was significantly longer in the yoga group. CONCLUSION: Our results suggest that practicing yoga activates the parasympathetic nervous system during the third trimester of pregnancy, consolidating sleep during the night and decreasing α-amylase levels, which indicates reduced stress.

Psychiatric diagnoses and their influencing factors in patients complaining of sleep problems: A study of a psychiatric consultation-liaison service.

Objective This study aimed to identify misdiagnosed or undiagnosed psychiatric disorders and the factors associated with these disorders in patients with sleep problems who are referred to a consultation-liaison service. Method Records of all inpatients receiving a consultation from the Psychiatry Department between January and December 2016 were retrospectively reviewed. Psychiatric diagnoses were analyzed using descriptive statistics, and the factors associated with the risk of these disorders in patients with sleep problems were determined by multiple logistic regression analysis. Results Of the 331 referral patients whose referral reason was simply having trouble in sleeping, only 97 patients were diagnosed with primary sleep disorder after consultation. The recognition rate of psychiatric disorders in inpatients with sleep problems among nonpsychiatric physicians was 29.3%. Anxiety (107, 45.7%) was the most common psychiatric diagnosis in patients with sleep problems followed by organic mental disorder (83, 35.5%), depression (37, 15.8%), and other mental disorders (8, 3.4%). Multiple logistic regression analysis revealed that a course >1 month (OR = 3.656, 95% CI = 2.171-6.156, p = 0.000) and sleep-wake rhythm disturbances (OR = 25.008, 95% CI = 5.826-107.341, p = 0.000) were associated with increased risks of psychiatric disorders. Conclusions The study showed that recognition rate of psychiatric disorders in inpatients with sleep problems was very low. A course >1 month and sleep-wake rhythm disturbances were associated with increased risks of disorders and could be used as indicators by nonpsychiatric physicians to improve diagnoses.

Clock Genes and Altered Sleep-Wake Rhythms: Their Role in the Development of Psychiatric Disorders.

In mammals, the circadian clocks network (central and peripheral oscillators) controls circadian rhythms and orchestrates the expression of a range of downstream genes, allowing the organism to anticipate and adapt to environmental changes. Beyond their role in circadian rhythms, several studies have highlighted that circadian clock genes may have a more widespread physiological effect on cognition, mood, and reward-related behaviors. Furthermore, single nucleotide polymorphisms in core circadian clock genes have been associated with psychiatric disorders (such as autism spectrum disorder, schizophrenia, anxiety disorders, major depressive disorder, bipolar disorder, and attention deficit hyperactivity disorder). However, the underlying mechanisms of these associations remain to be ascertained and the cause-effect relationships are not clearly established. The objective of this article is to clarify the role of clock genes and altered sleep-wake rhythms in the development of psychiatric disorders (sleep problems are often observed at early onset of psychiatric disorders). First, the molecular mechanisms of circadian rhythms are described. Then, the relationships between disrupted circadian rhythms, including sleep-wake rhythms, and psychiatric disorders are discussed. Further research may open interesting perspectives with promising avenues for early detection and therapeutic intervention in psychiatric disorders.

[Diabetes, dementia, depression, distress]. / Diabetes, dementia, depresszió, distressz.

The number of people living with diabetes continues to rise. Therefore neurologists or other health care practitioners may be increasingly faced with comorbid neuropsychiatric disorders commonly presented by diabetic patients. More recently there has been an increasing research interest not only in the interactions between diabetes and the nervous system, the fine structure and functional changes of the brain, but also in the cognitive aspects of antidiabetic treatments. Patients with both types of diabetes mellitus may show signs of cognitive decline, and depression. Comorbid insomnia, anxiety, and distress may also occur. The bidirectional relationships between all these phenomena as well as their connection with diabetes can lead to further health and quality of life deterioration. Therefore it is important that all practitioners involved in the care of diabetic patients recognize the presence of comorbid neuropsychiatric disturbances early on during the healthcare process. Identifying higher risk patients and early screening could improve the prognosis of diabetes and may prevent complications.

Assessment of cognitive function and sleep-wake rhythms in community-dwelling older adults.

Disruption of the circadian rhythm and sleep-wake cycles is a consequence of aging and is associated with the cognitive decline and many neurodegenerative conditions. We investigated the bedtime, wake-up time, sleep timing (midpoint between bedtime and wake-up time), and sleep timing standard deviation (SD) using the actigraphy among 80 consecutive volunteers aged ≥ 60 years. Global cognitive function and executive function of detailed cognitive domains were evaluated using the mini-mental state examination (MMSE) and Wisconsin card sorting test (WCST) and subjective daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). The category achievement (CA), total errors (TE), perseverative errors of Nelson (PEN), non-perseverative errors (NPE), and difficulties in maintaining set (DMS) on the WCST were significantly correlated with sleep timing SD (CA: r = - 0.276, p = 0.013, TE: r = 0.311, p = 0.005, PEN: r = 0.241, p = 0.032, NPE: r = 0.250, p = 0.025, DMS: r = 0.235, p = 0.036), but not with the MMSE score. Multiple regression analyses with the stepwise forward selection method including age, ESS score, bedtime, sleep timing, and sleep timing SD, revealed that the ESS score, and sleep timing SD were significant factors related to CA on the WCST (ESS score: ß = - 0.322, p = 0.004; sleep timing SD: ß = - 0.250, p = 0.022). Assessment of sleep-wake rhythms, daytime sleepiness, and cognitive function using the MMSE and WCST is valuable for the prediction of cognitive decline in the geriatric population.

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

OBJECTIVE/BACKGROUND: Idiopathic/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. METHODS: Participants 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. RESULTS: iRBD 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. CONCLUSIONS: This 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.

Managing non-24-hour sleep-wake rhythm disorder with ramelteon in a 12-year-old girl with Pierre Robin sequence and developmental delay: a case report.

The author recently observed a case involving a 12-year-old sighted girl who exhibited symptoms typical of non-24-hour sleep-wake rhythm disorder (N24SWD). This disorder, more commonly found in blind individuals, presents a unique challenge when diagnosed in those with vision. Several interventions can be attempted, ranging from behavioral adjustments to light therapy. Although melatonin has been noted for its effectiveness in realigning the patient's sleep-wake cycle, the use of ramelteon, a melatonin receptor agonist, has seldom been reported in managing N24SWD. However, this case illuminates the potential of ramelteon as another therapeutic option for sighted individuals with N24SWD. Further study is suggested to determine the potential of ramelteon in managing this disorder among sighted individuals of varying age groups. CITATION: Huang C-H. Managing non-24-hour sleep-wake rhythm disorder with ramelteon in a 12-year-old girl with Pierre Robin sequence and developmental delay: a case report. J Clin Sleep Med. 2024;20(6):995-997.

A tendency toward evening chronotype associates with less healthy diet among preschoolers: cross-sectional findings from the DAGIS study.

Study Objectives: Evidence suggests that adolescents and adults with a later chronotype have poorer sleep habits and are more susceptible to unhealthy behaviors, but little is known about these associations in younger children. The objective of the study was to (1) identify and compare individual chronotype tendencies among preschool-aged children and (2) investigate associations of sleep dimensions and chronotype with diet. Methods: Participants were 636 3-6 years old (mean ±â€…SD age: 4.74 ±â€…0.89 years, 49% girls) preschoolers from the cross-sectional Increased Health and Well-Being in Preschoolers (DAGIS) study in Finland. Sleep duration, sleep variability (in duration and midpoint), social jetlag, and midsleep on weekends adjusted for sleep debt (MSWEadj) were measured with 7-day actigraphy. Morning, intermediate, and evening chronotype tendencies were defined based on the lowest and highest 10th percentile cutoffs of MSWEadj. Food, energy, and macronutrient intake were assessed from 3-day records. Associations between sleep dimensions and diet were assessed with regression models. Results: MSWEadj was 1:13 ±â€…14 minutes for morning (n = 64), 2:25 ±â€…28 minutes for intermediate (n = 560), and 3:38 ±â€…15 minutes for evening (n = 64) chronotype tendency. Children with an evening chronotype tendency had greater social jetlag and sleep variability. Having an evening chronotype tendency was associated with higher added sugar, higher sugary food consumption, and lower vegetable consumption compared to intermediate tendency types. A later chronotype (MSWEadj) was associated with higher sugary food consumption, as well as lower vegetable and fiber intake. Sleep duration, social jetlag, and sleep variability were not associated with diet. Conclusions: Several less healthy sleep and diet behaviors were observed among children with later chronotypes. Future public health interventions aimed towards children would benefit from taking into account chronotype.

Registry and survey of circadian rhythm sleep-wake disorder patients.

Objective: Circadian Sleep Disorders Network has created a registry of circadian rhythm sleep-wake disorder (CRSWD) patients, and a survey of their experiences. The purpose of the registry is to provide volunteers willing to participate in research; the purpose of the survey is to fill some of the knowledge gaps on these disorders, including information on subjective patient experience and the efficacy and durability of treatments.Researchers are invited to contact Circadian Sleep Disorders Network for permission to use the registry to find potential research participants, and to further analyze the survey data. Patients: Over 1627 patients have participated; 1298 have completed the entire survey. Here we present results based on the 479 clinically diagnosed CRSWD patients. Methods: The survey covers a variety of topics relating to CRSWDs, including diagnosis, comorbidities, treatments, and work/educational accommodations. Conclusions: Results of this survey diverged from much of the literature. More than half the participants reported tiredness even when sleeping on their preferred schedule. While depression may cause sleep problems, our data suggests that sleep/circadian problems often precede depression.There were more people suffering from sighted non-24-hour sleep-wake rhythm disorder than some of the literature would lead us to expect.Current treatments did not appear to be helpful to a large percentage of our participants. Most of them did not find light therapy helpful and nearly all participants who tried phase-delay chronotherapy reported at best only short-term improvement. A sizable proportion of people who tried phase-delay chronotherapy subsequently developed non-24-hour sleep-wake rhythm disorder.

Long-term effects of melatonin on quality of life and sleep in haemodialysis patients (Melody study): a randomized controlled trial.

AIM: The disturbed circadian rhythm in haemodialysis patients results in perturbed sleep. Short term melatonin supplementation has alleviated these sleep problems. Our aim was to investigate the effects of long-term melatonin supplementation on quality of life and sleep. METHODS: In this randomized double-blind placebo-controlled trial haemodialysis patients suffering from subjective sleep problems received melatonin 3 mg day(-1) vs. placebo during 12 months. The primary endpoint quality of life parameter 'vitality' was measured with Medical Outcomes Study Short Form-36. Secondary outcomes were improvement of three sleep parameters measured by actigraphy and nighttime salivary melatonin concentrations. RESULTS: Sixty-seven patients were randomized. Forty-two patients completed the trial. With melatonin, no beneficial effect on vitality was seen. Other quality of life parameters showed both advantageous and disadvantageous effects of melatonin. Considering sleep, at 3 months sleep efficiency and actual sleep time had improved with melatonin compared with placebo on haemodialysis days (difference 7.6%, 95% CI 0.77, 14.4 and 49 min, 95% CI 2.1, 95.9, respectively). At 12 months none of the sleep parameters differed significantly from placebo. Melatonin salivary concentrations at 6 months had significantly increased in the melatonin group compared with the placebo group. CONCLUSIONS: The high drop-out rate limits the strength of our conclusions. However, although a previous study reported beneficial short term effects of melatonin on sleep in haemodialysis patients, in this long-term study the positive effects disappeared during follow up (6-12 months). Also the quality of life parameter, vitality, did not improve. Efforts should be made to elucidate the mechanism responsible for the loss of effect with chronic use.

Images: Irregular sleep-wake rhythm disorder in transgender individuals.

Growing evidence suggests that transgender individuals face a significant health disparity and are particularly vulnerable to sleep disorders. We present two patients who developed irregular sleep-wake rhythm disorder after gender reassignment and hormone replacement therapy. The growing interest in transgender health warrants further evaluation of the effects and frequency of all sleep disorders in this population. Efforts to address sleep disorders should consider assessing sleep disturbance in terms of sleep/wake patterns and schedules. CITATION: Kokash A, Vendrame M. Images: irregular sleep-wake rhythm disorder in transgender individuals. J Clin Sleep Med. 2023;19(11):1981-1984.