Genes for normal sleep and sleep disorders

Sleep and wakefulness are complex behaviors that are influenced by many genetic and environmental factors, which are beginning to be discovered. The contribution of genetic components to sleep disorders is also increasingly recognized as important. Point mutations in the prion protein, period 2, and the prepro-hypocretin/orexin gene have been found as the cause of a few sleep disorders but the possibility that other gene defects may contribute to the pathophysiology of major sleep disorders is worth in-depth investigations. However, single gene disorders are rare and most common disorders are complex in terms of their genetic susceptibility, environmental effects, gene-gene, and gene-environment interactions. We review here the current progress in the genetics of normal and pathological sleep.     

Molecular genetics of timing in intrinsic circadian rhythm sleep disorders

Recent advances in circadian biology are identifying key genes and the molecular clockworks they command. These biochemical systems provide new tools for evaluating clinically observed, intrinsic circadian rhythm sleep disorders. A striking example was last year's discovery of a point mutation in a human clock gene that produces a sleep phase syndrome. This finding suggested that other intrinsic sleep disorders may have genetic underpinnings, and that less debilitating variations in sleep/wake behavior may be revealed by molecular screening of known clock genes in broader human populations.     

Neuroscience-driven discovery and development of sleep therapeutics

Until recently, neuroscience has given sleep research and discovery of better treatments of sleep disturbances little attention, despite the fact that disturbed sleep has overwhelming impact on human health. Sleep is a complex phenomenon in which specific psychological, electrophysiological, neurochemical, endocrinological, immunological and genetic factors are involved. The brain as both the generator and main object of sleep is obviously of particular interest, which makes a neuroscience-driven view the most promising approach to evaluate clinical implications and applications of sleep research. Polysomnography as the gold standard of sleep research, complemented by brain imaging, neuroendocrine testing, genomics and other laboratory measures can help to create composite biomarkers that allow maximizing the effects of individualized therapies while minimizing adverse effects. Here we review the current state of the neuroscience of sleep, sleep disorders and sleep therapeutics and will give some leads to promote the discovery and development of sleep medicines that are better than those we have today.     

Molecular genetics of timing in intrinsic circadian rhythm sleep disorders

Recent advances in circadian biology are identifying key genes and the molecular clockworks they command. These biochemical systems provide new tools for evaluating clinically observed, intrinsic circadian rhythm sleep disorders. A striking example was last year's discovery of a point mutation in a human clock gene that produces a sleep phase syndrome. This finding suggested that other intrinsic sleep disorders may have genetic underpinnings, and that less debilitating variations in sleep/wake behavior may be revealed by molecular screening of known clock genes in broader human populations.     

Circadian rhythm sleep disorders

Individuals who have circadian rhythm sleep disorders present with symptoms of insomnia or excessive sleepiness and complain of an inability to sleep at their desired time. Although the primary etiology of these disorders is a misalignment between the endogenous circadian clock and the external environment, social and behavioral factors can also play important roles in perpetuating or exacerbating these disorders. Currently, the management of circadian rhythm disorders is limited to the use of bright light and melatonin to realign the circadian clock with the desired sleep time.However, as the understanding of the physiologic and genetic basis of sleep and circadian rhythm regulation advances, even more practical and effective treatments should become available.     

Women and sleep

Naturally fluctuating hormones (menstrual cycle, through pregnancy or menopausal transition) are not related to marked sleep disturbances in women. It is likely, however, that subsets of women will display a central nervous system vulnerability to hormonal fluctuations so that sleep disturbances manifest as a part of a complex of discomforting symptoms. Sleep is impacted directly through the circadian system or brain sleep regulation or through the development of concurrent functional changes and symptoms. Women are susceptible to sleep-related disorders that are also common in men, such as primary insomnia and SBD although the contributing factors and manifestations may not be the same.     

Clinical,anatomical, and physiologic relationship between sleep and headache

The intimate relationship between sleep and headache has been recognized for centuries, yet the relationship remains clinically and nosologically complex. Headaches associated with nocturnal sleep have often been perceived as either the cause or result of disrupted sleep. An understanding of the anatomy and physiology of both conditions allows for a clearer understanding of this complex relationship and a more rational clinical and therapeutic approach. Recent biochemical and functional imaging studies in patients with primary headache disorders has lead to the identification of potential central generators which are also important for the regulation of normal sleep architecture. Medical conditions (e.g. obstructive sleep apnea, depression) that may disrupt sleep and lead to nocturnal or morning headache can often be identified on clinical evaluation or by polysomnography. In contrast, primary headache disorders which often occur during nocturnal sleep or upon awakening, such as migraine, cluster headache, chronic paroxysmal hemicrania, and hypnic headache, can readily be diagnosed through clinical evaluation and managed with appropriate medication. These disorders, when not associated with co-morbid mood disorders or medications/analgesics overuse, seldom lead to significant sleep disruption. Identifying and classifying the specific headache disorder in patients with both headache and sleep disturbances can facilitate an appropriate diagnostic evaluation. Patients with poorly defined nocturnal or awakening headaches should undergo polysomnography to exclude a treatable sleep disturbance, especially in the absence of an underlying psychological disorder or analgesic overuse syndrome. In patients with a well defined primary headache disorder, unless there are compelling historical or examination findings suggestive of a primary sleep disturbance, a formal sleep evaluation is seldom necessary.     

Sleep studies for sleep apnoea

Sleep studies have grown to encompass a broad range of technologies employed to study and diagnose a variety of sleep disorders. From their inception in neurophysiology laboratories interested in investigating primary disorders of sleep architecture from psychiatric illness, their remit has widened such that their most common role is currently to diagnose secondary sleep disruption from respiratory, cardiovascular or other systemic causes. This review outlines the pathophysiology of obstructive sleep apnoea in particular and how sleep studies have improved our understanding of the complex dynamic changes in blood gas tensions, cardiovascular control and cerebral arousal that occur with these repetitive events. We review the historical development of standard laboratory-based sleep studies and discuss their limitations in staging sleep, reflecting the episodes of increased upper airway resistance that underlie these disorders and their ability to predict individuals' symptoms or response to medical or surgical therapies. We then describe some alternative signals that have been employed to monitor the physiological changes in upper airway resistance and arousal with a discussion of some of the evidence that these 'limited' studies may provide diagnostic information that can guide clinical decision making and may predict the outcome without the need, in some cases, for more complex and costly laboratory-based studies.     

Primary care assessment and management of sleep disorders

PURPOSE: To review the functions of sleep and describe an appropriate sleep assessment for the identification of sleep disorders for nurse practitioners (NP) in primary care. Guidelines for management and referral are included. DATA SOURCES: Selected and the author's experience. CONCLUSIONS: The incidence of sleep deprivation in the United States is generally unacknowledge by the public as well as health care professional. Unfortunately, the castastrophic and debilitating consequences that result from alterations in sleep are usually noted after significant physical and emotional damage have occurred. IMPLICATIONS FOR PRACTICE: An assessment of sleep hygiene and the physical, emotional, or lifestyle changes that alter sleep patterns should be a part of the NP's routine encounter with patients. Referral is indicated for suspicion of obstructive sleep apnea, narcolepsy, restless leg syndrome, complex motor activity, or if the condition fails to respond to therapeutic management.     

Molecular genetics of anxiety in mice and men

Human anxiety disorders represent one of the most common mental illnesses. They are complex diseases with both genetic and environmental factors affecting their predisposition. Since the basic neuronal mechanisms are shared across mammalian species, the same set of genes may regulate critical aspects of anxiety in humans and in lower species. In this review, we first summarize findings from human molecular genetic approaches to anxiety disorders or anxiety‐related personality traits: genome‐wide scans and candidate gene studies in large families or case‐control cohorts. We then discuss recent studies that have used genome‐wide methods in mouse strains to identify genes that regulate anxiety‐like behavior. Although it has been difficult to pinpoint specific susceptibility genes for anxiety disorders, ongoing efforts to collect larger study cohorts and to develop new genetic tools should help in this task. Studies in animals have shown that novel quantitative trait locus (QTL) and functional genomics approaches might lead to the identification of regulators of anxiety in mice, and that these genes can be tested for their involvement in human anxiety disorders. Finally, breakthroughs are expected in the fine‐mapping of human and mouse genetic linkage regions and in the identification of novel candidate genes using genome‐wide methods in mouse models of anxiety.     

Cluster headaches and sleep disorders

Cluster headaches are characterized by unilateral paroxysmal attacks of severe pain with associated symptoms. The headaches occur during particular sleep stages and are associated with other chronobiologic factors. Several sleep disorders have been associated with the occurrence of cluster headache; multiple hormonal influences affect the relationship between sleep and headache. Melatonin and other treatments that affect circadian rhythm have been suggested for the treatment of cluster headache. Obstructive sleep apnea can occur in patients with cluster headache; attempts to treat one disorder may influence the other. Sleep disorders such as insomnia and narcolepsy also may be associated with and influence cluster headaches. This article examines the relationship between the various sleep disorders and cluster headache, and reviews current research. Normal and abnormal sleep and details of treatments for specific sleep disorders that may decrease the frequency and severity of cluster headaches also are discussed. The relationship between obstructive sleep apnea, which is the most common sleep disorder, and cluster headache is discussed in detail.     

Classification and epidemiology of childhood sleep disorders

Approximately 25% of all children experience some type of sleep problem at some point during childhood. A number of studies have examined the prevalence of parent- and child-reported sleep complaints in large samples of healthy, typically developing children and adolescents; many of these have also further delineated the association between disrupted sleep and behavioral concerns. Sleep problems are even more prevalent in children and adolescents with chronic medical, neurodevelopmental, and psychiatric conditions. It is important to note that definitions of normal sleep patterns, sleep requirements, and sleep disorders in childhood must necessarily incorporate the wide range of normal developmental and physical maturational changes across childhood and adolescence, and cultural, environmental, and social influences.     

Definitions and clinical classifications of sleep disorders

Sleep disorders are defined as disorders which symptoms or pathophysiology are related with sleep regardless of comorbid physical and/or mental disorders. Sleep disorders are classified into 6 major categories: sleep related breathing disorders which exhibit abnormal breathing during sleep, sleep related movement disorders which show involuntary movements and/or abnormal sensations during sleep and/or nighttime, hypersomnia of central origin not due to other sleep disorders, circadian rhythm sleep disorders due to desynchronization between sleep-wake pattern and required social schedule, parasomnia which exhibit abnormal behavior during sleep and/or around sleep, and insomnia not due to other sleep disorders.     

睡眠节律紊乱与阿尔兹海默病研究进展

认知功能损害患者睡眠障碍患病率高,表现形式多样,主要包括：失眠、日间过度思睡、睡眠呼吸障碍、异态睡、不宁腿综合征、睡眠节律紊乱等。阿尔茨海默病(Alzheimer"s disease,AD)是最常见的认知损害类型,73%的中国汉族AD患者伴有睡眠障碍,其中53%伴有不同程度的睡眠节律紊乱。AD患者睡眠障碍在病程中后期较为突出,所以一直以来睡眠节律紊乱都被认为是AD相关神经退行性变的结果,例如“日落现象”,患者一到傍晚就焦虑不安、难以入睡,而白天则睡眠过多。但近期研究表明,睡眠节律紊乱很可能参与AD发生的始动环节。国外前瞻性的随访研究发现,睡眠节律紊乱的认知正常老年人群,在5-10年后更容易发生AD。目前,关于睡眠节律紊乱究竟通过何种途径促使神经系统退行性变发生的研究尚不深入,本文将回顾睡眠节律紊乱引发AD相关病理、生物标记物变化的研究报道。     

新型冠状病毒肺炎疫情下医护人员睡眠障碍影响因素的质性研究

目的深入了解新冠病毒肺炎疫情下医护人员出现睡眠障碍的原因,为改善其睡眠质量提供参考。方法采用目的抽样选取2020年1月26日—3月14日福建省第一批进入金银潭医院进行救治任务而出现睡眠障碍的10名医护人员为研究对象,以质性研究中Colaizzi现象学方法为指导,采用微信视频面对面访谈的方式了解医护人员出现睡眠障碍的原因。结果多种因素可影响医护人员的睡眠障碍,归纳为睡眠习惯的改变、对疫情的过分担心、环境和生活方式的改变、职业压力的影响、院感防护的影响。结论在新型冠状病毒肺炎疫情影响下一线医护人员睡眠质量不佳,应帮助医护人员从生理、心理各方面进行调节,提高其睡眠质量。     

The ecology of bipolar disorder: the importance of sleep

Although much of the emphasis in treating Bipolar Disorder patients is on pharmacotherapy, sleep loss is an important trigger for mania and plays an important role in the condition. The purpose of this paper is to fully explore the chronobiological, environmental, social, and genetic factors that contribute to the sleep disruption that is characteristic of mania and bipolar disorder. This review is important because sleep, chronobiology, and genetics are under-emphasized content areas in nursing education. As a result, many practicing nurses are unaware of the importance of sleep for mental health or what to teach patients to improve both the quality of their sleep and the management of their condition.     

Effect of smoke exposure on young adults' sleep quality

In this study, we aimed to examine the relationship between active smoking and environmental tobacco smoke exposure on sleep‐quality complaints. In total, 1023 young adult participants completed online surveys. Based on these surveys, participants were classified into three groups according to their level of smoke exposure (low, moderate, high). An analysis of covariance revealed that, after controlling for sex, participants with high and moderate smoke exposure reported more sleep complaints than those with low exposure. Among non‐smokers, hierarchical linear regression indicated that environmental tobacco smoke exposure was positively associated with sleep complaints. Improved understanding of modifiable risk factors for young adults' poor sleep quality, such as smoke exposure, could enable lifestyle changes that might lay the foundation for improved health at later life stages.     

睡眠节律紊乱导致阿尔兹海默病相关机制的研究进展

认知功能损害患者睡眠障碍患病率高,表现形式多样,主要包括失眠、日间过度思睡、睡眠呼吸障碍、异态睡、不宁腿综合征、睡眠节律紊乱等。阿尔茨海默病(Alzheimer disease,AD)是最常见的认知损害类型。73%的中国汉族AD患者伴有睡眠障碍,其中53%伴有不同程度的睡眠节律紊乱。AD患者睡眠障碍在病程后期较为突出,因此睡眠节律紊乱一直被认为是AD相关神经退行性变的结果,如"日落现象"。但近期研究表明,睡眠节律紊乱很可能参与AD发生的始动环节。国外前瞻性随访研究发现,认知正常老年人群睡眠节律紊乱发生5年后更易发生AD。目前,关于睡眠节律紊乱通过何种途径促使神经系统退行性变发生的研究尚不深入。本文对睡眠节律紊乱引发AD相关病理、生物标志物变化进而导致AD发生的机制作一综述。     

The relationship between sleep disorders and stroke

Although sleep appears to be a quiescent, passive state externally, there are a multitude of physiological changes occurring during sleep that can affect cerebral homeostasis and predispose individuals to cerebrovascular disorders. Therefore, it is not surprising that sleep-disordered breathing causes significant nocturnal perturbations, such as obstructive sleep apnea (OSA), that can lead to cerebrovascular disorders. There is evidence to suggest that OSA is a risk factor for stroke, although studies have not been able to clearly discern the absence or presence of OSA before the stroke event. Sleep-disordered breathing, such as OSA and central sleep apnea, can occur as a consequence of stroke. Fortunately, treating OSA appears to decrease morbidity and possibly mortality. Unfortunately, continuous positive airway pressure compliance in this population group is low, and significant efforts and resources may be needed to improve compliance and adherence. Various other sleep disorders, such as insomnia, fatigue, hypersomnia, and parasomnia, can occur following a stroke, and physicians treating patients following a stroke need to be aware of these disorders in order to effectively treat such patients.