Sleep and circadian schedule disorders

The timing and synchronization of human circadian rhythms is important for health and well-being. Some individuals, for reasons that remain unclear, display less resilience or flexibility in their ability to synchronize to the 24-hour world and are thus diagnosed with a circadian schedule disorder. The objective of this article is to briefly introduce concepts about human circadian timing and to review what is known about chronic, long-term circadian schedule disorders such as delayed sleep phase syndrome, advanced sleep phase syndrome, irregular sleep-wake patterns, and non-24-hour sleep-wake disorder. Practical considerations for the clinician caring for these individuals are discussed.     

Fibromyalgia and Sleep in Animal Models: A Current Overview and Future Directions

Sleep disorders are highly prevalent in patients with fibromyalgia (FM). Many of the daytime symptoms, such as chronic pain and fatigue, may be related to the non-restorative sleep patterns associated with the disease. Pain influences the sleep process and sleep disturbances decrease the pain threshold in a reciprocal framework. Thus, understanding the link between sleep and FM has become an important research topic in basic science. Therefore, in the current review we connect these topics and provide some insights into the cyclic relationship between sleep and pain, which has been addressed mainly in animal models. Additionally, we highlight the urgent need for sleep studies in FM animal models, which might improve the knowledge base and accelerate advances in this field.     

Biological basis for sleep disturbance and behavioral symptoms in dementia: a biobehavioral model

Behavioral symptoms and sleep disturbance occur in more than 56% of older adults with mild to moderate dementia and are challenging and costly. This article proposes a biobehavioral causal model to explain sleep disturbances and behavioral symptoms in dementia (BSD) based on an integrative science perspective using the life cycle model of stress (chronic stress) integrating genetic, neuroendocrine, and personality factors. The model proposes that: (a) BSD are an outcome of sleep disturbance; (b) hypothalamic-pituitary-adrenal (HPA) axis dysregulation is key to sleep disturbances and BSD; (c) genotype influences response to stress hormones; (d) HPA is influenced by genotype; (e) trait anxiety moderates the relationship between HPA axis and BSD and/or sleep disturbances; and (f) trait anxiety is influenced by genotype. Examining these relationships simultaneously will advance our theoretical understanding of BSD and sleep disturbances, potentially providing a basis for the design of targeted interventions and prevention strategies with an understanding of risk.     

Traditional chinese medicine for chronic fatigue syndrome

More and more patients have been diagnosed as having chronic fatigue syndrome (CFS) in recent years. Western drug use for this syndrome is often associated with many side-effects and little clinical benefit. As an alternative medicine, traditional Chinese medicine (TCM) has provided some evidences based upon ancient texts and recent studies, not only to offer clinical benefit but also offer insights into their mechanisms of action. It has perceived advantages such as being natural, effective and safe to ameliorate symptoms of CFS such as fatigue, disordered sleep, cognitive handicaps and other complex complaints, although there are some limitations regarding the diagnostic standards and methodology in related clinical or experimental studies. Modern mechanisms of TCM on CFS mainly focus on adjusting immune dysfunction, regulating abnormal activity in the hypothalamic-pituitary-adrenal (HPA) axis and serving as an antioxidant. It is vitally important for the further development to establish standards for 'zheng' of CFS, i.e. the different types of CFS pathogenesis in TCM, to perform randomized and controlled trials of TCM on CFS and to make full use of the latest biological, biochemical, molecular and immunological approaches in the experimental design.     

What happens to the fibromyalgia syndrome?]

OBJECTIVE: To realize a clarification about fibromyalgia, attempting to consider diagnostic criteria, prevalence, pathophysiology and therapeutic approach. METHOD: A systematic literature search was conducted to select articles about fibromyalgia and connected diseases. The database are Premedline, Medline and Medlineplus. RESULTS: Fifty-eight articles about fibromyalgia and twelve articles about connected diseases were selected to realize this review of literature. DISCUSSION: Fibromyalgia constitutes a syndrome characterized by widespread musculo-skeletal pain, present above the waist and below the waist and in the axial skeleton. Widespread pain must have been present for at least three months. "Spasmophilie", chronic fatigue syndrome and myofascial syndrome represent diseases connected with fibromyalgia: differential diagnosis must be established. Researches related to fibromyalgia suggest a reduction of muscular performances associated with histological and biochemical anomalies. Patients are characterized by shorter and nonrestorative sleep. Psychological, neuroendocrine and central alterations appear often associated with fibromyalgia. The reduction of pressure tolerance and pain thresholds may be linked to the alterations of neuroendocrine substances. Literature recommend a multidisciplinary therapeutic approach in management of fibromyalgia. CONCLUSION: The pathophysiologic mechanisms in fibromyalgia appear multiple and interdependent. With the aim to optimizing treatment, investigations are necessary to determine biochemical repercussions of various therapeutic approaches.     

Physiological and Psychological Fatigue in Extreme Conditions: Overtraining and Elite Athletes

This article will review relevant mechanisms and markers associated with overtraining syndrome (OTS), and discuss signs and symptoms, differential diagnosis, and current assessment tools for fatigue within the context of overtraining. The findings are drawn from original research and review articles referenced by PubMed and ScienceDirect databases. Sources were selected for their contributions to the current knowledge of biological, psychological, and molecular mechanisms. Data were reviewed for relevance to OTS and then evaluated against criteria that included significant OTS outcomes and findings. Information was systematically analyzed to identify patterns, dependencies, connections, and causal factors. Comparative analysis was confounded by inconsistent metrics, terminology, and variable methodology; potential biomarkers, treatment and prevention approaches, and future research directions are identified. Diagnosing OTS is difficult because underlying cause(s) are unknown; one must exclude other factors that degrade performance and mood status. Many studies are confounded by inadequate experimental designs, poor measures of performance, and different methods for characterizing OTS. OTS is complex because the demands of excessive training in combination with other biologic, psychological, and social stressors are difficult to quantify. However, changes in mood are always noted. Interrelations among dietary patterns; social, psychological and physiological profiles; and the neuroendocrine, immune, and central nervous systems are complex and not adequately elucidated.     

Fibromyalgia Syndrome

Fibromyalgia is a chronic rheumatologic disorder. The primary symptoms include musculoskeletal pain and aching, disturbed sleep, fatigue, morning stiffness, and local tenderness. It is frequently misdiagnosed, despite being a fairly common, chronic disorder in most primary care clinics. Failure to make this diagnosis often leads to unnecessary medical and surgical treatment. The treatment of fibromyalgia syndrome is multifaceted. Goals include reassurance, education about pain management and modification, and symptom reduction. Exercise may be beneficial. Amitriptyline is effective in reducing certain symptoms of fibromyalgia, such as pain and lack of restful sleep. Narcotics, steroids, and nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided.     

宫颈癌同步放化疗患者治疗后癌因性疲乏症状体验的质性研究

目的深入了解行同步放化疗的宫颈癌患者治疗后癌因性疲乏(cancer-related fatigue,CRF)的真实体验,以期为医护人员有针对性地实施干预提供依据,为宫颈癌同步放化疗患者CRF症状的管理与控制提供研究基础。方法 2016年1-6月,采用现象学研究方法,通过目的抽样对12名行同步放化疗的宫颈癌患者进行半结构式访谈,运用Colaizzi 7步分析法对资料进行分析。结果归纳出7个主题,即CRF在同步放化疗的宫颈癌患者中普遍存在且多维度、CRF有相关的伴随症状、CRF影响患者的心理状态、CRF影响患者的睡眠、患者存在对疲劳症状理解的误区、患者需要社会支持、患者有向医护人员寻求缓解疲乏症状的诉求。结论 CRF症状是主观且多维度的,医护人员应在宫颈癌患者同步放化疗的多个阶段进行疲乏及疲乏相关症状的评估与干预,以缓解患者的疲乏症状,提升其应对疾病的能力。     

Self-reported subjective sleep quality and fatigue in patients with peritoneal dialysis treatment at home

The aim of this study was to describe habitual sleep, daytime symptoms, sleep-disturbing factors, current sleep during 1 week and fatigue in patients with peritoneal dialysis treatment at home and also discover predictions for sleep quality outcome. The knowledge should increase possibilities for supportive nursing health care. Fifty-five patients answered two mailed questionnaires and filled in a sleep diary. Of these, 60% had moderate, persistent sleep problems combined with daytime symptoms. Nocturnal awakenings with difficulties falling asleep again and a sleep duration predicted as 57% of sleep quality. Nocturnal pruritus and 'difficulties finding a comfortable sleeping position' were significant sleep-disturbing factors. Sleep quality predictors means progress in knowledge about the complexity of the situation for peritoneal dialysis patients. Poor sleep, daytime symptoms, sleep-disturbing factors and chronic fatigue need to be enlightened, especially for the nephrology nurses who are in a unique position to give supportive nursing health care.     

Neuroendocrine abnormalities in fibromyalgia

Fibromyalgia is a disorder of unknown etiology characterized by chronic, widespread musculoskeletal pain and symptoms such as fatigue, poor sleep, gastrointestinal complaints, and psychologic problems that are similar to those experienced by patients with hormone deficiencies. This review summarizes the available data on the neuroendocrine function in fibromyalgia, including data on hormone secretion, circadian phase, and autonomic nervous system function. Studies suggest that there may be lower activity of a number of hypothalamic-pituitaryperipheral gland axes and altered autonomic nervous system function in patients with fibromyalgia. These reductions in activity are mild to moderate and do not result from alterations in circadian rhythms. The reduced hormonal and autonomic responses appear to reflect an impairment in the hypothalamic or central nervous system response to stimuli rather than a primary defect at the level of the pituitary gland or the peripheral glands. A combination of multiple, mild impaired responses may lead to more profound physiologic and clinical consequences as compared with a defect in only one system, and could contribute to the symptoms of fibromyalgia.     

Chronic fatigue syndrome.

Fatigue is one of the most common complaints among patients seen in the primary care setting. Chronic fatigue syndrome, which has recently been called chronic fatigue immune dysfunction syndrome, is distinctive, with an abrupt onset of symptoms that wax and wane for at least six months. Usually there is low-grade fever, pharyngitis and tender, but not enlarged, lymph nodes. The fatigue can be disabling and is often made worse by physical activity. Some patients with this disorder have also been found to have highly characteristic immunologic abnormalities. Treatment can be rewarding and is based on patient education and support, exercise and symptomatic therapies for abnormal sleep patterns, musculoskeletal pain and other symptoms.     

Violence, stress, and somatic syndromes

Syndromes characterized by pain, fatigue, mood disorder, cognitive dysfunction, and sleep disturbance have been referred to as stress-related somatic disorders by virtue of the observation that onset and exacerbation of symptoms occur with stress. These syndromes include but are not limited to fibromyalgia, chronic fatigue syndrome, temporomandibular disorder, and irritable bowel syndrome. As with most chronic illnesses, genetic susceptibility and lifetime environmental exposures play a role in creating vulnerability to disease. Cumulative lifetime stress has been associated with a number of physiologic changes in the brain and body that reflect dysregulated hormonal and autonomic activity. Exposure to the stressor of violence is likely to create a state of vulnerability for the stress-related somatic syndromes and also to contribute to symptom expression and severity. Understanding the relationship between violence, stress, and somatic syndromes will help in clarifying the consequences of violence exposure to long-term health and health-related quality of life.     

Night eating syndrome

Night eating syndrome (NES), an eating disorder that has been linked to obesity, was first described in 1955. It occurs when the normally synchronous patterns of energy intake and sleep become disrupted; the result of this dysynchrony is a relative phase delay between the disordered eating patterns and the normal sleep-wake cycles. Although specific criteria for NES have not yet been validated, the characteristic associated behaviors are evening hyperphagia, morning anorexia, and insomnia. This article reviews NES prevalence, behavioral and neurohormonal manifestations of this disorder, criteria for its differential diagnosis, and current treatment options.     

Pharmacologic treatment of fibromyalgia

Fibromyalgia is a chronic syndrome characterized by widespread pain, unrefreshed sleep, disturbed mood, and fatigue. Until such time as we have a clearer understanding of the trigger and/or pathophysiologic mechanisms producing these symptoms, pharmacologic treatment should be aimed at individual symptoms. Such treatment should ideally be offered as part of a multidisciplinary treatment program using both pharmacologic and nonpharmacologic treatment modalities. Critical components of any successful fibromyalgia treatment program include addressing physical fitness, work and other functional activities, and mental health, in addition to symptom-specific therapies. The main symptoms that should be addressed include pain, sleep disturbances including restless leg syndrome, mood disturbances, and fatigue. Pharmacologic therapy should also be considered for syndromes commonly associated with fibromyalgia including irritable bowel syndrome, interstitial cystitis, migraine headaches, temporomandibular joint dysfunction, dysequilibrium including neurally mediated hypotension, sicca syndrome, and growth hormone deficiency. This article provides general guidelines in initiating a successful pharmacologic treatment program for fibromyalgia.     

Objective and subjective assessment of sleep in adolescents with chronic pain compared to healthy adolescents

OBJECTIVES: The purpose of this study was to compare sleep of adolescents with chronic pain and healthy adolescents using both subjective and objective sleep assessments, and to identify correlates of poor sleep. METHODS: Forty adolescents (n=20 with chronic pain and n=20 healthy adolescents), aged 12 to 17 years (72.5% female) participated. Adolescents completed self-report measures of pain, sleep quality and hygiene, presleep arousal/worry, and depressive symptoms. Sleep patterns were assessed over 7 consecutive days using an actigraph, a motion-monitoring device detecting sleep-wake patterns by measuring activity levels. Total sleep time, sleep efficiency, wake time, and wake bouts were derived from the actigraph and aggregated for analysis. RESULTS: Compared with healthy peers, adolescents with chronic pain demonstrated similar total sleep time as healthy adolescents, but significantly poorer sleep. In particular, adolescents with chronic pain subjectively reported poorer sleep quality and increased insomnia symptoms, and demonstrated lower actigraphic sleep efficiency and more wake bouts compared with their healthy peers. Depressive symptoms and worry at bedtime were significant predictors of subjectively reported sleep quality but not of actigraphic sleep. DISCUSSION: Adolescents with chronic pain evidenced poorer sleep quality, increased insomnia symptoms, and less efficient sleep with more wake bouts in comparison with healthy adolescents, findings that require replication in a larger sample. Assessment and management of sleep disturbances is an important aspect of care for children and adolescents with chronic pain.     

A comparison of disrupted sleep patterns in women with cancer-related fatigue and postmenopausal women without cancer

Purpose

Fatigue and disrupted sleep often coexist and both are prominent clinical problems in cancer affecting quality of life. Disrupted sleep patterns are likely related to cancer-related fatigue. The relationship needs further investigation. This study aimed to characterize and compare disrupted sleep patterns in fatigued breast cancer patients receiving chemotherapy with postmenopausal women without a history of cancer. Anxiety levels were also examined.

Methods

Data for this secondary analysis came from two studies. Global sleep quality and state anxiety were self-reported by 30 fatigued female breast cancer chemotherapy outpatients and 32 non-cancer postmenopausal women using Pittsburgh Sleep Quality Index (PSQI) and State-Trait Anxiety Inventory, respectively.

Results

Fatigued breast cancer patients showed significant sleep difficulties, characterized by prolonged sleep onset latency (M = 54.3, SD = 49.2 min) and frequent nighttime awakenings, despite 40% of the patients using sleep medications three or more times a week. Compared to the non-cancer comparison group, fatigued patients reported significantly longer sleep latency (p = 0.041), more use of sleep medications (p = 0.006), and higher total PSQI scores (p = 0.005). State anxiety levels did not differ between the two groups (p = 0.88).

Conclusions

Sleep is disrupted in fatigued breast cancer women undergoing chemotherapy. Nearly all fatigued patients (97%) had trouble sleeping (global PSQI scores > 5), indicating significant difficulties in overall sleep quality among those patients. Knowledge of the nature of sleep disruption among cancer patients may contribute to CRF symptom management leading to tailored interventions designed to improve sleep quality in cancer patients thereby managing fatigue and improving quality of life.     

Duloxetine and Pregabalin for Pain Management in Multiple Rheumatic Diseases Associated with Fibromyalgia

The fibromyalgia syndrome (FMS) is characterized by chronic and widespread musculoskeletal pain and soreness accompanied by sleep disorders, chronic fatigue and affective disorders. FMS is often associated with other forms of immuno‐rheumatic diseases. Although FMS pathophysiology is still not fully understood, a number of neuroendocrine, neurotransmission and neurosensitive disorders might generate a mechanism for the elicitation of pain by “central sensitization,” which is common to many other painful conditions. The present case describes the success of a therapeutic scheme, which associates two different pharmacological classes, anticonvulsants and new‐generation antidepressants, when FMS complicates a rare pathology called Cogan's syndrome. The association of two drugs might noticeably affect the molecular mechanisms of difficult pain, thus solving painful conditions of multifactorial origin.     

From human to mouse and back offers hope for patients with fibromyalgia

Fibromyalgia syndrome (FMS) is a highly prevalent, debilitating disease with heterogeneous symptoms of widespread pain and tenderness, fatigue, sleep disturbance, and impaired cognition. The cause of FMS is unknown, but the clinical constellation of symptoms and abnormalities in the neuroendocrine system, autonomic nervous system, and sleep implicate the nervous system in its pathogenesis. In this issue of the JCI, Goebel, Krock, et al. identified antibodies from patients with FMS that produce FMS in mice by binding to satellite glial cells (SGCs), which envelope sensory neurons. Because antibodies harvested from patients with FMS, but not controls, stimulated SGCs to an activated state known to mediate chronic pain by augmenting neuronal activity, these findings reveal a pivotal role for autoreactive IgG in the pathophysiology of FMS. These important findings pave a pathway to study mechanism-based experimental therapeutics targeting IgG titers or antibody binding to SGCs underlying the neuroimmune dysfunction of FMS.     

The effects of alprazolam on corticotropin-releasing factor neurons in the rat brain: acute time course, chronic treatment and abrupt withdrawal.

Considerable evidence indicates that corticotropin-releasing factor (CRF) is responsible for integrating not only the endocrine, but the autonomic and behavioral responses of an organism to stress. We have investigated the time course of action of the anxiolytic triazolobenzodiazepine, alprazolam, on the activity of the hypothalamic-pituitary-adrenal (HPA) axis and of CRF neurons after acute and chronic administration. In addition, because many of the signs and symptoms observed in animals and humans after abrupt discontinuation of benzodiazepines resemble the stress response, we examined the effect of alprazolam withdrawal on CRF neurons and HPA axis activity. Alprazolam decreases CRF concentrations in the locus coeruleus between 0.5 and 3.0 h following acute injection. The half-life of alprazolam in rats is less than 1 h in both plasma and brain. Similarly, chronic (14 days) alprazolam administration also results in decreased CRF concentrations in the locus coeruleus. CRF concentrations return to control values 24 h after abrupt withdrawal. Moreover, abrupt alprazolam withdrawal results in increased plasma adrenocorticotrophic hormone and corticosterone concentrations and decreased anterior pituitary CRF receptor concentrations 24 h after drug discontinuation. These indices return to control values by 48 h postwithdrawal. These results support the hypothesis that both acute and chronic alprazolam administration alters CRF-containing neurons innervating the locus coeruleus. Additionally, abrupt alprazolam withdrawal profoundly activates the HPA axis.