Skin disorders and sleep in adults: Where is the evidence?

Sleep deprivation has been shown to have detrimental effects on behavioural, physiological and psychological functioning. Skin disorders are variably associated with sleep disturbance and sleep deprivation, some associated with specific sleep disorders such as obstructive sleep apnoea. Paradoxically, there is very little literature focussed on the management of sleep problems in the context of skin disorders. Furthermore, randomised controlled trials of treatments for skin conditions are few and rarely measure sleep as an outcome, either subjectively or objectively. This review focuses on common skin disorders and how they affect sleep.     

The significance of sleep physiological disturbances in depression

Since the discovery of the antidepressant effects of interventions in the sleep-wake cycle, a number of hypotheses have emerged according to which disturbances in sleep physiology are not merely expressions but essential components of the pathophysiology of depression. Three hypotheses are presented, the "Phase-advance", the "S-deficiency" and the "ACh-hypersensitivity" hypotheses. They explain the therapeutic effects of total, partial and selective sleep deprivation as consequences of the normalization of disturbed sleep regulation. The question is dealt with whether there are indications that the hypothesized sleep regulatory disturbances exist and whether there is a relationship between the effects of sleep deprivation on sleep regulation and clinical state. None of the hypotheses is totally supported, none can be fully rejected.     

Sleep and Substance Use Disorders: An Update

Substance use disorders (SUD) are common and individuals who suffer from them are prone to relapse. One of the most common consequences of the use of and withdrawal from substances of abuse is sleep disturbance. Substances of abuse affect sleep physiology, including the neurotransmitter systems that regulate the sleep-wake system. Emerging research now highlights an interactive effect between sleep disorders and substance use. New findings in alcohol and sleep research have utilized sophisticated research designs and expanded the scope of EEG and circadian rhythm analyses. Research on marijuana and sleep has progressed with findings on the effects of marijuana withdrawal on objective and subjective measures of sleep. Treatment studies have focused primarily on sleep in alcohol use disorders. Therapies for insomnia in cannabis disorders are needed. Future research is poised to further address mechanisms of sleep disturbance in alcoholics and the effect of medical marijuana on sleep and daytime functioning.     

The contribution of intermittent hypoxia, sleep debt and sleep disruption to daytime performance deficits in children: consideration of respiratory and non-respiratory sleep disorders

In children, the most abundant available information regarding the effects of paediatric sleep disturbance on daytime function has been obtained by studying children with sleep disordered breathing (SDB). The purported underlying pathophysiological mechanisms responsible for these deficits include hypoxia secondary to obstructive apneas/hypopneas and/or disrupted sleep architecture from frequent arousals during sleep. This review will present evidence that, while hypoxia is likely to play a role for many children with SDB, sleep disruption is an important and often overlooked factor that can contribute to daytime deficits in children with SDB. Indeed, sleep deprivation and disruption appear to have a potent impact on the daytime functioning of the much larger number of children with non-respiratory sleep disorders. It is concluded that sleep deprivation, sleep disruption, and intermittent hypoxia independently may be sufficient to cause daytime effects in vulnerable children, and the combination of two or more of these factors can result in particularly impaired daytime functioning. These conclusions have significant implications for research and clinical practice.     

Cytokines and sleep

Personal experience and empirical data indicate sleep is altered during sickness. Important signaling molecules of the peripheral immune system called cytokines orchestrate responses to infection. Through a variety of mechanisms, the brain detects activation of the peripheral immune system. The brain responds to infection by altering physiological processes and complex behavior, including sleep. These changes in physiology and behavior collectively function to support the immune system, and under normal circumstances the health of the host is restored. Several of these cytokines, and their receptors, are present in normal healthy brain. Some cytokines regulate sleep under physiological conditions, in the absence of infection or immune challenge. For example, interleukin-1 directly alters discharge patterns of neurons in hypothalamic and brainstem circuits implicated in the regulation of sleep-wake behavior. Many other cytokines modulate sleep because they interact with neurotransmitter, peptide, and/or hormone systems to initiate a cascade of responses that subsequently alter sleep-wake behavior. Because cytokines regulate/modulate sleep-wake behavior in the absence of immune challenge, and cytokine concentrations and profiles are altered during infection, it is likely that cytokines mediate infection-induced alterations in sleep. Whether the changes in sleep that occur during infection are beneficial and aid in recovery remains to be determined.     

Effects of sleep and sleep loss on immunity and cytokines

Sleep is hypothesized to be a restorative process that is important for the proper functioning of the immune system. Severity of disordered sleep in depressed- and alcoholic subjects correlates with declines in natural- and cellular immunity and is associated with alterations in the complex cytokine network. Sleep loss has a role in mediating these immune changes as experimentally induced partial night sleep deprivation replicates the kind of sleep loss found in clinical samples and induces a pattern of immune alterations similar to that found in depressed- and alcoholic patients. Despite evidence that sleep and sleep loss have effects on immune processes and nocturnal secretion of cytokines, the clinical significance of these immune changes is not known. Moreover, in view of basic evidence of a reciprocal interaction between sleep and cytokines, further research is needed to understand whether alterations in cytokines contribute to disordered sleep in patient populations.     

Experimental studies on the interaction between sleep and the immune system in humans

Sleepiness and increased sleep pressure are typical symptoms of inflammation and infection. Moreover, it is a pre-scientific belief that sleep supports host defense. The present paper summarizes the experimental evidence regarding the interaction between sleep and the immune system in humans. Sleep-wake behavior is very sensitive to experimental host defense activation, for example, by bacterial endotoxin. When the injection of endotoxin is accompanied by fever and a prominent neuroendocrine activation, sleep continuity will be disturbed. When the production of inflammatory cytokines is stimulated by smaller amounts of endotoxin, but no fever and no neuroendocrine activation are apparent, the nonREM-sleep amount will increase. This is possibly due to changes in the biological activity of the tumor necrosis factor-alpha (TNF-alpha) system. Besides their important function in sleep regulation during acute immune response, cytokines also seem to be involved in physiological sleep regulation, although there still is not very much data on this issue. So far, it remains largely unknown whether or not sleep supports host defense. In humans, for example, acute sleep deprivation up to 55 hours has only minor effects on endotoxin-induced host responses. In contrast, there is preliminary and yet inconsistent evidence that sleep deprivation might impair antibody formation in response to viral challenges.     

The role of actigraphy in sleep medicine

During the last decade actigraphy (activity-based monitoring) has become an essential tool in sleep research and sleep medicine. The validity, reliability and limitations of actigraphy for documenting sleep-wake patterns have been addressed. Normative data on sleep-wake patterns across development have been collected. Multiple studies have documented the adequacy of actigraphy to distinguish between clinical groups and to identify certain sleep-wake disorders. Actigraphy has also been shown to be effective in documenting the effects of various behavioral and medical interventions on sleep-wake patterns. Actigraphy is less useful for documenting sleep-wake in individuals who have long motionless periods of wakefulness (e.g. insomnia patients) or who have disorders that involve altered motility patterns (e.g. sleep apnea). Potential users should be aware of a number of pitfalls of actigraphy: (1) validity has not been established for all scoring algorithms or devices, or for all clinical groups; (2) actigraphy is not sufficient for diagnosis of sleep disorders in individuals with motor disorders or high motility during sleep; (3) the use of computer scoring algorithms without controlling for potential artifacts can lead to inaccurate and misleading results.     

Autonomic Dysfunction in Sleep Disorders: From Neurobiological Basis to Potential Therapeutic Approaches

Sleep disorder has been portrayed as merely a common dissatisfaction with sleep quality and quantity. However, sleep disorder is actually a medical condition characterized by inconsistent sleep patterns that interfere with emotional dynamics, cognitive functioning, and even physical performance. This is consistent with sleep abnormalities being more common in patients with autonomic dysfunction than in the general population. The autonomic nervous system coordinates various visceral functions ranging from respiration to neuroendocrine secretion in order to maintain homeostasis of the body. Because the cell population and efferent signals involved in autonomic regulation are spatially adjacent to those that regulate the sleep-wake system, sleep architecture and autonomic coordination exert effects on each other, suggesting the presence of a bidirectional relationship in addition to shared pathology. The primary goal of this review is to highlight the bidirectional and shared relationship between sleep and autonomic regulation. It also introduces the effects of autonomic dysfunction on insomnia, breathing disorders, central disorders of hypersomnolence, parasomnias, and movement disorders. This information will assist clinicians in determining how neuromodulation can have the greatest therapeutic effects in patients with sleep disorders.     

The sleep therapies of depression

This paper reviews five different types of deliberate sleep-wake manipulations which are reported to have antidepressant effects: total sleep deprivation, partial sleep deprivation, a phase advance of the sleep periods, and REM deprivation. The effects of total sleep deprivation are best documented. Of 852 depressed patients studied, 493 or 57.9% improved following sleep deprivation. The REM deprivation procedure acts more slowly, but is of more lasting clinical value than the other forms. Partial sleep deprivation during the second half of the night may be as good as total sleep deprivation and better tolerated. The findings are reviewed in terms of psychological, neurophysiological, biochemical, and chronobiological perspectives.     

Neuroimaging in sleep medicine

The development of neuroimaging techniques has made possible the characterization of cerebral function throughout the sleep-wake cycle in normal human subjects. Indeed, human brain activity during sleep is segregated within specific cortical and subcortical areas in relation to the sleep stage, sleep physiological events and previous waking activity. This approach has allowed sleep physiological theories developed from animal data to be confirmed, but has also introduced original concepts about the neurobiological mechanisms of sleep, dreams and memory in humans. In contrast, at present, few neuroimaging studies have been dedicated to human sleep disorders. The available work has brought interesting data that describe some aspects of the pathophysiology and neural consequences of disorders such as insomnia, sleep apnea and narcolepsy. However, the interpretation of many of these results is restricted by limited sample size and spatial/temporal resolution of the employed technique. The use of neuroimaging in sleep medicine is actually restrained by concerns resulting from the technical experimental settings and the characteristics of the diseases. Nevertheless, we predict that future studies, conducted with state of the art techniques on larger numbers of patients, will be able to address these issues and contribute significantly to the understanding of the neural basis of sleep pathologies. This may finally offer the opportunity to use neuroimaging, in addition to the clinical and electrophysiological assessments, as a helpful tool in the diagnosis, classification, treatment and monitoring of sleep disorders in humans.     

Functional neuroimaging of sleep

Sleep and sleep disorders have traditionally been viewed from a polysomnographic perspective. Although these methods provide information on the timing of various stages of sleep and wakefulness, they do not provide information regarding function in brain structures that have been implicated in the generation of sleep and that may be abnormal in different sleep disorders. Functional neuroimaging methods provide information regarding changes in brain function across the sleep-wake cycle that provides information for models of sleep dysregulation in a variety of sleep disorders. Early studies show reliable increases in function in limbic and anterior paralimbic cortex in rapid eye movement (REM) sleep and decreases in function in higher-order cortical regions in known thalamocortical networks during non-REM sleep. Although most of the early work in this area has been devoted to the study of normal sleep mechanisms, a collection of studies in diverse sleep disorders such as sleep deprivation, depression, insomnia, dyssomnias, narcolepsy, and sleep apnea suggest that functional neuroimaging methods have the potential to clarify the pathophysiology of sleep disorders and to guide treatment strategies.     

Behavioural treatments for sleep problems in children and adolescents with physical illness,psychological problems or intellectual disabilities

Young people with physical, psychological or intellectual disabilities or disorders are reported to have more frequent and persistent problems with sleep than their peers without . Sleep disorders affecting the quantity or quality of sleep have effects on a child's daytime functioning and the functioning of their families. Many children with special needs have learning and behaviour problems and their parents (particularly mothers) have increased levels of stress and poorer mental health. This relationship between sleep disorders and learning, and behaviour and family functioning makes it particularly important that children with special needs receive appropriate intervention for their sleep disorders. This may be one way of mitigating these other problems. This review considers the case reports and experimental trials which have used behavioural treatments for sleep problems in children and adolescents with special needs. Behavioural treatments for sleep-wake cycle disorders, sleeplessness, parasomnias and excessive sleepiness are reported. These preliminary reports do suggest that behavioural approaches can be rapidly successful for treating sleep problems, even where the sleep problems are long-standing, severe and associated with physical, psychological or intellectual problems. The parent and the clinician should not be deterred from treating the sleep problem in isolation using behavioural treatments. Methodological issues, however, highlight the importance of further and better research. Not all children responded to the behavioural interventions and some needed re-implementation of therapy to maintain improvements; the use of heterogeneous groups make the findings and choice of treatment for individuals difficult to interpret. Finally, there are few studies overall, and the majority are case studies rather than controlled studies using multiple baseline designs or randomization and a control group. Careful studies are required in order to establish the relative efficacy of the behavioural techniques and their suitability with homogeneous subgroups of children with special needs.     

Pineal volume and evening melatonin in young people with affective disorders

Affective disorders in young people have been associated with disruptions in circadian rhythms, including abnormalities in secretion of the pineal hormone melatonin. Previous research reports relationships between pineal gland volumes, melatonin secretion, and sleep-wake cycles, but the relationship between these factors has not been explored in affective disorders. This study aimed to characterize these factors and explore associations with mood symptoms and functioning in a sample of young people with affective disorders. Pineal volume from magnetic resonance imaging and melatonin assay from evening dim-light saliva collection were evaluated in 50 individuals (15–30 years old; 72 % female) with bipolar, depressive, or anxiety disorders. Actigraphy monitoring was also conducted for approximately two weeks to derive sleep-wake measures. Pineal volume was associated with melatonin secretion across the evening, replicating previous findings in psychiatrically healthy individuals. Pineal volume was smaller in participants in which melatonin onset was not detected. Timing of melatonin secretion was related to sleep timing, but amount of melatonin and pineal volume were not related to any sleep-wake measures. A shorter phase angle between onset of melatonin secretion and sleep onset was associated with longer total sleep time. Lower melatonin levels were associated with poorer social and occupational functioning. Although pineal volume is not directly related to sleep disturbances or symptoms, melatonin may influence both sleep-wake cycles and functioning in the early stages of affective disorder. Causal links remain to be established, however, treatments that target circadian rhythms may be useful in improving functioning in young people with affective disorders.     

48-hour sleep-wake cycles in manic-depressive illness: naturalistic observations and sleep deprivation experiments

Wrist motor activity and sleep were monitored longitudinally in 15 rapidly cycling and 52 nonrapidly cycling manic-depressive patients. The majority of patients experienced one or more consecutive 48-hour sleep-wake cycles (alternate nights with no sleep) when they switched out of depression into mania of hypomania. During a depressive phase, nine rapidly cycling patients were asked to simulate a 48-hour sleep-wake cycle by remaining awake for 40 hours (one night's total sleep deprivation). Eight switched out of depression, and seven were rated as manic or hypomanic; indicating that sleep loss (such as occurs with spontaneous 48-hour sleep-wake cycles) may help to trigger switches from depression to mania. The 48-hour sleep-wake cycles in patients may depend on a mechanism that is normally present in all humans, since normal persons also spontaneously experience near-48 hour sleep-wake cycles in certain experimental conditions.     

Periodic movements in sleep (nocturnal myoclonus): Relation to sleep disorders

Periodic movements in sleep (PMS) are stereotyped, repetitive, nonepileptiform movements of the lower extremities. A total of 409 sleep disorder patients were studied with all-night polysomnogram recording, and 53 (13%) had PMS. Such movements occurred in a wide variety of sleep-wake disorders in addition to insomnia. The prevalence and magnitude of PMS were not statistically greater in patients with insomniac disorders than in those with syndromes of excessive daytime sleepiness or other sleep-wake disorders. The results suggest that although PMS is responsible for disturbed sleep in relatively few patients, chronic sleep-wake disturbance is associated with PMS and may lead to the development of these movements.     

Genetics of normal and pathological sleep in humans

The complexity of sleep-wake regulation, in addition to the many environmental influences, includes genetic predisposing factors, which begin to be discovered. Most of the current progress in the study of sleep genetics comes from animal models (dogs, mice, and drosophila). Multiple approaches using both animal models and different genetic techniques are needed to follow the segregation and ultimately to identify 'sleep genes' and molecular bases of sleep disorders. Recent progress in molecular genetics and the development of detailed human genome map have already led to the identification of genetic factors in several complex disorders. Only a few genes are known for which a mutation causes a sleep disorder. However, single gene disorders are rare and most common disorders are complex in terms of their genetic susceptibility, environmental factors, gene-gene, and gene-environment interactions. We review here the current progress in the genetics of normal and pathological sleep and suggest a few future perspectives.     

Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders

Recent evidence shows that the temporal alignment between the sleep-wake cycle and the circadian pacemaker affects self-assessment of mood in healthy subjects. Despite the differences in affective state between healthy subjects and patients with psychiatric disorders, these results have implications for analyzing diurnal variation of mood in unipolar and bipolar affective disorders and sleep disturbances in other major psychiatric conditions such as chronic schizophrenia. In a good proportion of patients with depression, mood often improves over the course of the day; an extension of waking often has an antidepressant effect. Sleep deprivation has been described as a treatment for depression for more than 30 years, and approximately 50% to 60% of patients with depression respond to this approach, especially those patients who report that their mood improves over the course of the day. The mechanisms by which sleep deprivation exerts its antidepressant effects are still controversial, but a reduction in rapid eye movement sleep (REM sleep), sleep pressure and slow-wave sleep (SWS), or a circadian phase disturbance, have been proposed. Although several studies support each of these hypotheses, none is sufficient to explain all observations reported to date. Unfortunately, the disturbed sleep-wake cycle or behavioural activities of depressed patients often explain several of the abnormalities reported in the diurnal rhythms of these patients. Thus, protocols that specifically manipulate the sleep-wake cycle to unmask the expression of the endogenous circadian pacemaker are greatly needed. In chronic schizophrenia, significant disturbances in sleep continuity, REM sleep, and SWS have been consistently reported. These disturbances are different from those observed in depression, especially with regard to REM sleep. Circadian phase abnormalities in schizophrenic patients have also been reported. Future research is expected to clarify the nature of these abnormalities.