Disturbed EEG sleep, paranoid cognition and somatic symptoms identify veterans with post-traumatic stress disorder.

BACKGROUND: Chronic post-traumatic stress disorder (PTSD) behavioural symptoms and medically unexplainable somatic symptoms are reported to occur following the stressful experience of military combatants in war zones. AIMS: To determine the contribution of disordered EEG sleep physiology in those military combatants who have unexplainable physical symptoms and PTSD behavioural difficulties following war-zone exposure. METHOD: This case-controlled study compared 59 veterans with chronic sleep disturbance with 39 veterans with DSM-IV and clinician-administered PTSD Scale diagnosed PTSD who were unresponsive to pharmacological and psychological treatments. All had standardised EEG polysomnography, computerised sleep EEG cyclical alternating pattern (CAP) as a measure of sleep stability, self-ratings of combat exposure, paranoid cognition and hostility subscales of Symptom Checklist-90, Beck Depression Inventory and the Wahler Physical Symptom Inventory. Statistical group comparisons employed linear models, logistic regression and chi-square automatic interaction detection (CHAID)-like decision trees. RESULTS: Veterans with PTSD were more likely than those without PTSD to show disturbances in non-rapid eye movement (REM) and REM sleep including delayed sleep onset, less efficient EEG sleep, less stage 4 (deep) non-REM sleep, reduced REM and delayed onset to REM. There were no group differences in the prevalence of obstructive sleep apnoeas/hypopnoeas and periodic leg movements, but sleep-disturbed, non-PTSD military had more EEG CAP sleep instability. Rank order determinants for the diagnosis of PTSD comprise paranoid thinking, onset to REM sleep, combat history and somatic symptoms. Decision-tree analysis showed that a specific military event (combat), delayed onset to REM sleep, paranoid thinking and medically unexplainable somatic pain and fatigue characterise chronic PTSD. More PTSD veterans reported domestic and social misbehaviour. CONCLUSIONS: Military combat, disturbed REM/non-REM EEG sleep, paranoid ideation and medically unexplained chronic musculoskeletal pain and fatigue are key factors in determining PTSD disability following war-zone exposure. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Patient safety, resident well-being and continuity of care with different resident duty schedules in the intensive care unit: a randomized trial.

BACKGROUND: Shorter resident duty periods are increasingly mandated to improve patient safety and physician well-being. However, increases in continuity-related errors may counteract the purported benefits of reducing fatigue. We evaluated the effects of 3 resident schedules in the intensive care unit (ICU) on patient safety, resident well-being and continuity of care. METHODS: Residents in 2 university-affiliated ICUs were randomly assigned (in 2-month rotation-blocks from January to June 2009) to in-house overnight schedules of 24, 16 or 12 hours. The primary patient outcome was adverse events. The primary resident outcome was sleepiness, measured by the 7-point Stanford Sleepiness Scale. Secondary outcomes were patient deaths, preventable adverse events, and residents' physical symptoms and burnout. Continuity of care and perceptions of ICU staff were also assessed. RESULTS: We evaluated 47 (96%) of 49 residents, all 971 admissions, 5894 patient-days and 452 staff surveys. We found no effect of schedule (24-, 16- or 12-h shifts) on adverse events (81.3, 76.3 and 78.2 events per 1000 patient-days, respectively; p = 0.7) or on residents' sleepiness in the daytime (mean rating 2.33, 2.61 and 2.30, respectively; p = 0.3) or at night (mean rating 3.06, 2.73 and 2.42, respectively; p = 0.2). Seven of 8 preventable adverse events occurred with the 12-hour schedule (p = 0.1). Mortality rates were similar for the 3 schedules. Residents' somatic symptoms were more severe and more frequent with the 24-hour schedule (p = 0.04); however, burnout was similar across the groups. ICU staff rated residents' knowledge and decision-making worst with the 16-hour schedule. INTERPRETATION: Our findings do not support the purported advantages of shorter duty schedules. They also highlight the trade-offs between residents' symptoms and multiple secondary measures of patient safety. Further delineation of this emerging signal is required before widespread system change. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT00679809.

Effects of bedtime very low dose cyclobenzaprine on symptoms and sleep physiology in patients with fibromyalgia syndrome: a double-blind randomized placebo-controlled study.

OBJECTIVE: To determine the effects of bedtime very low dose (VLD) cyclobenzaprine (CBP) on symptoms and sleep physiology of patients with fibromyalgia (FM), unrefreshing sleep, and the α-nonREM sleep electroencephalographic (EEG) anomaly at screening. METHODS: Of 37 patients with FM in the screened population, 36 were randomized and treated in this 8-week, double-blind, placebo-controlled, dose-escalating study of VLD CBP 1-4 mg at bedtime. We evaluated changes in subjective symptoms including pain, tenderness, fatigue, mood [Hospital Anxiety and Depression Scale (HAD)], and objective EEG sleep physiology (at screening, baseline, and Weeks 2, 4, and 8). RESULTS: In the VLD CBP-treated group (n = 18) over 8 weeks, musculoskeletal pain and fatigue decreased, tenderness improved; total HAD score and the HAD depression subscore decreased; patient-rated and clinician-rated fatigue improved. In the placebo-treated group (n = 18), none of these outcome measures changed significantly. Compared to placebo at 8 weeks, VLD CBP significantly improved pain, tenderness, and the HAD Depression subscore. Analysis of cyclic alternating pattern (CAP) sleep EEG revealed that significantly more subjects in the VLD CBP group than the placebo group had increased nights of restorative sleep in which CAP(A2+A3)/CAP(A1+A2+A3) = CAP(A2+A3(Norm)) ≤ 33%. For VLD CBP-treated subjects, the increase in nights with CAP(A2+A3(Norm)) ≤ 33% was correlated to improvements in fatigue, total HAD score, and HAD depression score. CONCLUSION: Bedtime VLD CBP treatment improved core FM symptoms. Nights with CAP(A2+A3(Norm)) ≤ 33% may provide a biomarker for assessing treatment effects on nonrestorative sleep and associated fatigue and mood symptoms in persons with FM.

Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study.

BACKGROUND: The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood. METHODS: Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia. RESULTS: Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms. CONCLUSIONS: The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.

Effects of sodium oxybate on sleep physiology and sleep/wake-related symptoms in patients with fibromyalgia syndrome: a double-blind, randomized, placebo-controlled study.

OBJECTIVE: To determine the effects of sodium oxybate (SXB) on sleep physiology and sleep/wake-related symptoms in patients with fibromyalgia syndrome (FM). METHODS: Of 304 patients with FM (American College of Rheumatology tender point criteria) in the screened study population, 209 underwent polysomnography, 195 were randomized, and 151 completed this 8-week, double-blind, placebo-controlled study of SXB 4.5 g and 6 g/night. We evaluated changes in objective sleep measures and subjective symptoms, including daytime sleepiness [Epworth Sleepiness Scale (ESS)], fatigue visual analog scale (FVAS), sleep [Jenkins Scale for Sleep (JSS)], and daytime functioning [Functional Outcome of Sleep Questionnaire (FOSQ), SF-36 Vitality domain, and Fibromyalgia Impact Questionnaire (FIQ) general and morning tiredness]. RESULTS: Pretreatment screening revealed an elevated incidence of maximum alpha EEG-intrusion > 24 min/hour of sleep (66%), periodic limb movements of sleep (20.1% ≥ 5/hour), and moderate to severe obstructive sleep apnea disorder (15.3% apnea-hypopnea index ≥ 15/hour). Compared with placebo, both doses of SXB achieved statistically significant improvements in ESS, morning FVAS, JSS, FOSQ, SF-36 Vitality, and FIQ general and morning tiredness; both doses also demonstrated decreased rapid eye movement (REM) sleep (all p ≤ 0.040). SXB 6 g/night improved afternoon, evening and overall FVAS, reduced wakefulness after sleep onset, and increased Stage 2, slow-wave, and total non-REM sleep (all p ≤ 0.032) versus placebo. Moderate correlations (≥ 0.40) were noted between changes in subjective sleep and pain measures. Adverse events occurring significantly more frequently with SXB than placebo were nausea, pain in extremity, nervous system disorders, dizziness, restlessness, and renal/urinary disorders (including urinary incontinence). CONCLUSION: This large cohort of patients with FM demonstrated that SXB treatment improved EEG sleep physiology and sleep-related FM symptoms.

Effect of duloxetine in patients with fibromyalgia: tiredness subgroups.

INTRODUCTION: This study tested the hypothesis that baseline ratings of fatigue/tiredness would be negatively associated with the efficacy of duloxetine on measures of pain and functional ability in patients with fibromyalgia. METHODS: A post hoc analysis of pooled data from 4 double-blind, placebo-controlled studies of duloxetine in fibromyalgia was performed. The fibromyalgia impact questionnaire (FIQ) tiredness item score (0 to 10 scale) was used to define tiredness subgroups. Patients were stratified into 3 subgroups: mild (0 to 3), moderate (4 to 6), and severe (7 to 10) tiredness. Analysis of covariance models and logistic regressions were used to test treatment-by-tiredness subgroup interactions. RESULTS: Data from the first 3 months are included in this post hoc analysis (duloxetine N = 797, placebo N = 535). At baseline, the distribution of tiredness severity in the duloxetine and placebo groups respectively was 3.64% and 3.75% mild, 16.71% and 15.57% moderate, and 79.65% and 80.68% severe. Rates of clinically significant (≥30% and ≥50%) improvement in brief pain inventory (BPI) average pain were similar across the tiredness subgroups. Tiredness severity at baseline was not negatively associated with the effects of duloxetine on patients' reports of functional ability using the FIQ total score, FIQ measures of physical impairment, interference with work, pain, stiffness, and depression and the medical outcomes study short form-36 (SF-36). CONCLUSIONS: Studies of duloxetine in fibromyalgia have demonstrated clinically significant improvements in pain and functional ability (FIQ, SF-36). This post hoc analysis of data shows that the efficacy of duloxetine among patients with fibromyalgia does not vary as a function of baseline ratings of fatigue/tiredness.

Rheumatic manifestations of sleep disorders.

PURPOSE OF REVIEW: We have long assumed that rheumatic pain causes sleep problems, fatigue, and functional disability. This paper reviews the accumulating evidence from human and animal experimental research studies that show a bidirectional relationship of disordered sleep to pain and fatigue. RECENT FINDINGS: The studies demonstrate that both disturbances of sleep and sleep restriction result in increased sensitivity to noxious stimuli and musculoskeletal pain symptoms. The notion of central nervous system hypersensitivity affecting widespread pain in patients with fibromyalgia syndrome is the result of a reduction in neurophysiologic inhibition of perception of noxious stimuli that is provoked by disordered sleep. Clinical and epidemiological studies show that sleep disturbances directly influence musculoskeletal pain, fatigue, mood, and overall well-being. Indeed, the interrelationships of the sleeping/waking brain with cytokine and cellular immune functions have important implications for the understanding of rheumatic disease pathology and management with disease-modifying antirheumatic drugs. SUMMARY: The determination of how disordered sleep affects musculoskeletal pain, fatigue, mood, and behavior is important in the assessment and management of patients with rheumatic illness. The high prevalence of obstructive sleep apnea and restless legs syndromes requires more research to determine whether treatments of these sleep disorders will benefit the symptoms of rheumatic diseases.

The significance of dysfunctions of the sleeping/waking brain to the pathogenesis and treatment of fibromyalgia syndrome.

This article reviews how functional disturbances of the sleeping-waking brain are involved in pathogenesis of the widespread pain, unrefreshing sleep, fatigue, and impaired quality of life of patients who have fibromyalgia syndrome. Recent studies of the effects on EEG sleep by some specific pharmacologic and physical therapeutic agents demonstrate not only benefit for the widespread pain and fatigue, but also improved sleep physiology and restorative sleep of patients who suffer from fibromyalgia.

A 1-year safety and efficacy study of duloxetine in patients with fibromyalgia.

OBJECTIVES: Evaluate the efficacy and safety of duloxetine at doses up to 120 mg once daily in patients with fibromyalgia. METHODS: This was a phase 3, 60-week study, which included an 8-week open-label period followed by a 52-week, randomized, double-blind period. Patients received duloxetine 30 mg daily for 1 week and duloxetine 60 mg daily for 7 weeks and were then randomized to receive either 60 or 120 mg daily (1:2 ratio). RESULTS: Enrolled patients (N=350, 95.7% female) exhibited moderate disease symptoms at study entry (Brief Pain Inventory average pain=6.7, Clinical Global Impression of Severity=4.1, and Patient's Global Impression of Severity=4.1). Significant pain reduction in patients was observed during the open-label study phase. This pain reduction continued during the 52-week double-blind study phase, as demonstrated by additional mean decreases in the Brief Pain Inventory average pain score within both duloxetine groups. The most common (> or =15%) treatment-emergent adverse events (overall phase) were nausea, headache, insomnia, dizziness, constipation, and dry mouth. Seventy-four (21.1%) patients reported adverse events as a reason for discontinuation [most common (>1%) were insomnia, vomiting, diarrhea, dizziness, and nausea]. The mean change (SD) in sitting systolic blood pressure (mm Hg) was -0.1 (14.4), in sitting diastolic blood pressure was -0.2 (9.6), in sitting pulse rate was 1.9 (10.4) bpm, and in weight was 0.7 (4.3) kg. DISCUSSION: The profile of duloxetine for the long-term treatment of fibromyalgia was consistent with that seen in other indications for which the drug is currently marketed.

Ottawa Panel evidence-based clinical practice guidelines for aerobic fitness exercises in the management of fibromyalgia: part 1.

BACKGROUND AND PURPOSE: The objective of this study was to create guidelines for the use of aerobic fitness exercises in the management of adult patients (>18 years of age) with fibromyalgia, as defined by the 1990 American College of Rheumatology criteria. METHODS: Following Cochrane Collaboration methods, the Ottawa Methods Group found and synthesized evidence from comparative controlled trials and formed the Ottawa Panel, with nominated experts from key stakeholder organizations. The Ottawa Panel then developed criteria for grading the recommendations based on experimental design (I for randomized controlled trials, II for nonrandomized studies) and strength of evidence (A, B, C+, C, D+, D, or D-). From the rigorous literature search, 13 randomized control trials and 3 controlled clinical trials were selected. Statistical analysis was based on Cochrane Collaboration methods. Continuous data were calculated with weighted mean differences between the intervention and control groups, and dichotomous data were analyzed with relative risks. Clinical improvement was calculated using absolute benefit and relative difference in change from baseline. Clinical significance was attained when an improvement of 15% relative to a control was found. RESULTS: There were 24 positive recommendations: 10 grade A, 1 grade B, and 13 grade C+. Of these 24 positive recommendations, only 5 were of clinical benefit. DISCUSSION AND CONCLUSION: The Ottawa Panel recommends aerobic fitness exercises for the management of fibromyalgia as a result of the emerging evidence (grades A, B, and C+, although most trials were rated low quality) shown in the literature.

Ottawa Panel evidence-based clinical practice guidelines for strengthening exercises in the management of fibromyalgia: part 2.

BACKGROUND AND PURPOSE: The objective of this study was to create guidelines for the use of strengthening exercises in the management of adult patients (>18 years of age) with fibromyalgia (FM), as defined by the 1990 American College of Rheumatology criteria. METHODS: Following Cochrane Collaboration methods, the Ottawa Methods Group found and synthesized evidence from comparative controlled trials and formed the Ottawa Panel, with nominated experts from key stakeholder organizations. The Ottawa Panel then developed criteria for grading the recommendations based on experimental design (I for randomized controlled trials, II for nonrandomized studies) and strength of evidence (A, B, C+, C, D+, D, or D-). From the rigorous literature search, 5 randomized controlled trials were selected. Statistical analysis was based on Cochrane Collaboration methods. Continuous data were calculated with weighted mean differences between the intervention and control groups, and dichotomous data were analyzed with relative risks. Clinical improvement was calculated using absolute benefit and relative difference in change from baseline. Clinical significance was attained when an improvement of 15% relative to a control was found. RESULTS: There were 5 positive recommendations: 2 grade A and 3 grade C+. All 5 were of clinical benefit. DISCUSSION AND CONCLUSION: The Ottawa Panel recommends strengthening exercises for the management of fibromyalgia as a result of the emerging evidence (grades A, B, and C+, although most trials were rated low quality) shown in the literature.

The significance of the sleeping-waking brain for the understanding of widespread musculoskeletal pain and fatigue in fibromyalgia syndrome and allied syndromes.

The clinical focus of rheumatologists on the widespread pain and numerous tender points in specific anatomic regions in their patients who show no evidence for disease pathology has lead to the characterization of such peripheral symptoms as a specific disorder of the musculoskeletal system, now commonly known as fibromyalgia. This rheumatologic diagnostic entity has resulted in relative inattention to an understanding of their patients' common complaints of unrefreshing sleep, chronic fatigue and psychological distress. Experimental evidence from humans and animal studies indicate that there is an inter-relationship of disturbances in the physiology of the sleeping-waking brain with the widespread musculoskeletal pain, chronic fatigue, and psychological distress in patients with hitherto unexplained pain/fatigue illnesses, e.g., fibromyalgia and chronic fatigue syndromes. The emerging knowledge of the dysfunction of the nervous system in such patients has lead to the study of novel medications that affect neurotransmitter functions, e.g., pregabalin, serotonin/noradrenaline compounds and sodium oxybate that are shown to improve many of the symptoms of such patients.

The significance, assessment, and management of nonrestorative sleep in fibromyalgia syndrome.

People with fibromyalgia syndrome (FMS) experience unrefreshing sleep, aches, hypersensitivity, and cognitive and emotional difficulties. Although no specific causative factor or biological agent is known to account for all of the features of FMS and these related diagnoses, the generalized hypersensitivity of the body is considered to be affected by disturbances in central nervous system (CNS) functions. Such CNS disturbances are intrinsic to the sleeping-waking brain, where the common symptom elements in all these illnesses are poor quality of sleep, nonspecific pain, fatigue, and psychological distress in the absence of known disease pathology.

Insecure attachment is associated with the alpha-EEG anomaly during sleep.

BACKGROUND: The alpha-EEG anomaly during sleep, originally associated with chronic pain, is noted in several psychiatric and medical conditions and is also present in some normal subjects. The exact significance of the alpha-EEG anomaly is uncertain, but it has been suggested to be a nonspecific response to a variety of noxious stimuli. We propose that attachment insecurity, which is often associated with a state of hypervigilance during wakefulness, may be associated with the alpha-EEG anomaly during sleep. METHODS: Thirty one consecutive patients referred to a Sleep Disorders Clinic for clinical assessment of sleep complaints underwent standard polysomnographic recording. The degree of alpha activity in polysomnographs was scored visually according to standard criteria. Attachment insecurity was measured with the Experience in Close Relationships - Revised questionnaire. RESULTS: Attachment anxiety was significantly associated with the proportion of sleep in which alpha waves were present (df = 1, F = 5.01, p = 0.03). The relationship between the alpha-EEG anomaly and attachment anxiety was not explained by the distribution of sleep and mood diagnoses, medications, anxiety symptoms or depression symptoms. CONCLUSION: Interpersonal style in close relationships may be related to sleep physiology. Further research to determine the nature of the relationship between attachment, sleep and other factors that are related to each of these, such as a history of personal adversity, is warranted.

Children with autism: effect of iron supplementation on sleep and ferritin.

To determine if there is a relationship between low serum ferritin and sleep disturbance in children with autism spectrum disorder, an 8-week open-label treatment trial with oral iron supplementation was conducted as a pilot study. At baseline and posttreatment visits, parents completed a Sleep Disturbance Scale for Children and a Food Record. Blood samples were obtained. Thirty-three children completed the study. Seventy-seven percent had restless sleep at baseline, which improved significantly with iron therapy, suggesting a relationship between sleep disturbance and iron deficiency in children with autism spectrum disorder. Sixty-nine percent of preschoolers and 35% of school-aged children had insufficient dietary iron intake. Mean ferritin increased significantly (16 microg/L to 29 microg/L), as did mean corpuscular volume and hemoglobin, suggesting that low ferritin in this patient group resulted from insufficient iron intake. Similar prevalence of low ferritin at school age as preschool age indicates that children with autism spectrum disorder require ongoing screening for iron deficiency.

Fatigue in systemic lupus erythematosus: contributions of disordered sleep, sleepiness, and depression.

OBJECTIVE: To clarify the role of sleep disorders, sleepiness, and depression in patients with systemic lupus erythematosus (SLE) who complain of disabling tiredness. METHODS: Patients with SLE (31 women, 4 men) with disabling tiredness were evaluated with the Epworth Sleepiness Scale (ESS) and overnight polysomnography, followed by daytime multiple sleep latency tests (MSLT) and the Beck Depression Inventory (BDI). Their polysomnography was compared with 17 healthy, asymptomatic controls. RESULTS: Polysomnography of the patients in comparison with healthy controls showed impaired sleep efficiency (p < 0.02), high arousal frequencies (p < 0.01), increased stage 1 sleep (p < 0.02), decreased stage 3/4 slow-wave sleep (p < 0.02), and a high percentage (77% of patients) with increased alpha-EEG non-REM sleep. In 23% of patients periodic limb movement (PLM) disorder was observed (mean PLM index 31.1 +/- 15); 26% of patients had obstructive sleep apnea (mean apnea/hypopnea index 19.3 +/- 10), and one patient had narcolepsy-cataplexy. Remarkably, 51% of patients were excessively sleepy on both the ESS and MSLT (mean sleep latency < 10 min). This excessive daytime sleepiness was not related to sleep restriction. There was no association between sleepiness and SLE disease features such as neuropsychiatric SLE, medications, fibromyalgia, or disease activity. As a whole, the study group reported mild to moderate depression (mean BDI = 15.8 +/- 9.9). Within the group, the sleepy patients had lower BDI scores than the non-sleepy patients (p < 0.02), and fewer of the sleepy patients were depressed (p < 0.04). CONCLUSION: Primary sleep disorders, sleepiness, and depression are common in tired SLE patients. Tiredness in SLE that is the result of excessive daytime sleepiness can be distinguished from tiredness of depression. Such distinctions will help identify appropriate treatment for tired patients with SLE.

Sleep disturbance induced by substance P in mice.

UNLABELLED: Substance P (SP) and neurokinins have been implicated in modulating pain and mood but little is known about their effect on sleep-wake behavior. The purpose of the present study was to examine the possible involvement of SP in sleep-wake mechanisms without activation of painful responses. Electrophysiological recordings of the sleep-wake cycle were conducted in C57BL/6J male mice that had intracerebral ventricular cannula inserted for drug administration. Initially, in order to determine the highest dose of SP that would not induce nociceptive response, 10 animals per group received administration of either SP doses or artificial cerebrospinal fluid (CSF-sham group) through the cannula and were assessed by the hot plate test. The sleep-wake cycle of two other groups of mice was recorded for 24 h before (baseline) and after receiving CSF (n=10) or SP-1 mM (n=11), dose that had been determined in the previous hot plate test. SP interfered with sleep, when compared to baseline and to sham group, by reducing sleep efficiency, increasing latency of sleep and the number of awakening bouts. To examine the reversal of SP effects, eight mice were administered with an NK1 receptor antagonist before SP administration. Prior administration of the NK1 antagonist prevented the disturbances in sleep. CONCLUSIONS: The results suggest that SP produces disturbances in sleep, likely mediated by the NK1 receptor.

Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity.

The orexin-2/hypocretin-2 (OX2R) receptor gene is mutated in canine narcolepsy and disruption of the prepro-orexin/hypocretin ligand gene results in both an animal model of narcolepsy and sporadic cases of the human disease. This evidence suggests that the structure of the OX2R gene, and its homologue, the OX1R gene, both members of the G protein-coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the prepro-orexin/hypocretin gene, may be variables in the etiology of sleep disorders. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in idiopathic sleep disorder patients diagnosed with excessive daytime sleepiness (EDS) (n = 28), narcolepsy (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two EDS patients showed a Pro11Thr change. One Tourette's syndrome patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non-disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild-type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (etaM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by EDS.

Special considerations in insomnia diagnosis and management: depressed, elderly, and chronic pain populations.

Patients with insomnia who also have chronic pain or depression or who are elderly represent segments of the population that are particularly difficult to treat. These populations tend to be at higher risk for experiencing difficulty sleeping and are more likely to experience chronic insomnia, sleep maintenance problems, and/or nonrestorative sleep. Worsening insomnia may exacerbate other somatic and psychological symptoms and vice versa. Conversely, there is evidence that appropriate recognition and management of the sleep complaint may alleviate other symptoms related to the associated condition and help interrupt this vicious cycle.