Treatments for somnambulism in adults: assessing the evidence

Somnambulism, or sleepwalking, is a parasomnia of non-rapid eye movement (NREM) sleep where movement behaviours usually confined to wakefulness are displayed during sleep. Generally, if sleepwalking is causing distress or danger in spite of safety measures, medical or psychological treatment is indicated. Clinicians will need to assess the evidence for treatment options. MEDLINE, EMBASE, PsycINFO and the Ovid Evidence–Based Medicine Reviews (EBM) multifile databases were searched. No properly powered rigorous controlled trials were found for treatment of sleepwalking in adults. Seven reports described small trials with some kind of control arm, or retrospective case series which included 30 or more patients. With no high quality evidence to underpin recommendations for treatments of somnambulism, full discussion with patients is advised. Adequately powered, well-designed clinical trials are now needed, and multi-centre collaborations may be required to obtain the sample sizes required

Obstructive sleep apnea and depression

There are high rates of depression in people with obstructive sleep apnea (OSA) in both community and clinical populations. A large community study reported a rate of 17% and reports for sleep clinic samples range between 21% and 41%. A large cohort study found OSA to be a risk factor for depression, but we are unaware of any longitudinal study of the reverse association. However correlations have not generally been found in smaller studies. Several possible causal mechanisms linking OSA and depression have been proposed but not established. Patients who have depression as well as OSA appear worse off than those with OSA only, and depressive symptoms persist in at least some patients in short term studies of treatment for OSA. Direct treatment of depression in OSA might improve acceptance of therapy, reduce sleepiness and fatigue and improve quality of life, but intervention trials are required to answer this question

Sleep apnoea and metabolic dysfunction.

Obstructive sleep apnoea (OSA) is a highly prevalent condition often associated with central obesity. In the past few years, several studies have analysed the potential independent contribution of OSA to the pathogenesis of metabolic abnormalities, including type 2 diabetes, the metabolic syndrome and nonalcoholic fatty liver disease. New perspectives in OSA patient care have been opened by the promotion of lifestyle interventions, such as diet and exercise programmes that could improve both OSA and the metabolic profile. The rich clinical literature on this subject, together with the growing amount of data on pathophysiological mechanisms provided by animal studies using the chronic intermittent hypoxia model, urged the organising Committee of the Sleep and Breathing meeting to organise a session on sleep apnoea and metabolic dysfunction, in collaboration with the European Association for the Study of Diabetes. This review summarises the state-of-the-art lectures presented in the session, more specifically the relationship between OSA and diabetes, the role of OSA in the metabolic consequences of obesity, and the effects of lifestyle interventions on nocturnal respiratory disturbances and the metabolic profile in OSA patient

Effects of 8 weeks of CPAP on lipid-based oxidative markers in obstructive sleep apnea: a randomized trial

Dyslipidaemia and increased oxidative stress have been reported in severe obstructive sleep apnea, and both may be related to the development of cardiovascular disease. We have previously shown in a randomized crossover study in patients with moderate to severe obstructive sleep apnea that therapeutic continuous positive airway pressure treatment for 8 weeks improved postprandial triglycerides and total cholesterol when compared with sham continuous positive airway pressure. From this study we have now compared the effect of 8 weeks of therapeutic continuous positive airway pressure and sham continuous positive airway pressure on oxidative lipid damage and plasma lipophilic antioxidant levels. Unesterified cholesterol, esterified unsaturated fatty acids (cholesteryl linoleate: C18:2; and cholesteryl arachidonate: C20:4; the major unsaturated and oxidizable lipids in low-density lipoproteins), their corresponding oxidized products [cholesteryl ester-derived lipid hydroperoxides and hydroxides (CE-O(O)H)] and antioxidant vitamin E were assessed at 20:30 hours before sleep, and at 06:00 and 08:30 hours after sleep. Amongst the 29 patients completing the study, three had incomplete or missing [CE-O(O)H] data. The mean apnea -hypopnoea index, age and body mass index were 38 per hour, 49 years and 32 kg m(-2) , respectively. No differences in lipid-based oxidative markers or lipophilic antioxidant levels were observed between the continuous positive airway pressure and sham continuous positive airway pressure arms at any of the three time-points [unesterified cholesterol 0.01 mm, P > 0.05; cholesteryl linoleate: C18:2 0.05 mm, P > 0.05; cholesteryl arachidonate: C20:4 0.02 mm, P = 0.05; CE-O(O)H 2.5 nm, P > 0.05; and lipid-soluble antioxidant vitamin E 0.03 μm, P > 0.05]. In this study, accumulating CE-O(O)H, a marker of lipid oxidation, does not appear to play a role in oxidative stress in obstructive sleep apnea.National Health and Medical Research Council project grant 30193

The effects of a single mild dose of morphine on chemoreflexes and breathing in obstructive sleep apnea

The effect of morphine on breathing and ventilatory chemoreflexes in obstructive sleep apnea (OSA) is unknown. It has been assumed that acute morphine use may induce deeper respiratory depression in OSA but this has not been investigated. We evaluated awake ventilatory chemoreflexes and overnight polysomnography on 10 mild-moderate OSA patients before and after giving 30 mg oral controlled-release morphine. Morphine plasma concentrations were analysed. We found a 30-fold range of morphine plasma concentrations with the fixed dose of morphine, and a higher plasma morphine concentration was associated with a higher CO(2) recruitment threshold (VRT) (r=0.86, p=0.006) and an improvement in sleep time with Sp(O(2)) (T90) (r=-0.87, p=0.005) compared to the baseline. The improvement in T90 also significantly correlated with the increase of VRT (r=-0.79, r=0.02). In conclusion, in mild-to-moderate OSA patients, a single common dose of oral morphine may paradoxically improve OSA through modulating chemoreflexes. There is a large inter-individual variability in the responses, which may relate to individual morphine metabolism.David Wang, Andrew A. Somogyi, Brendon J. Yee, Keith K. Wong, Jasminder Kaur, Paul J. Wrigley, Ronald R. Grunstei

Centromere Silencing and Function in Fission Yeast Is Governed by the Amino Terminus of Histone H3

AbstractBackground: Centromeric domains often consist of repetitive elements that are assembled in specialized chromatin, characterized by hypoacetylation of histones H3 and H4 and methylation of lysine 9 of histone H3 (K9-MeH3). Perturbation of this underacetylated state by transient treatment with histone deacetylase inhibitors leads to defective centromere function, correlating with delocalization of the heterochromatin protein Swi6/HP1. Likewise, deletion of the K9-MeH3 methyltransferase Clr4/Suvar39 causes defective chromosome segregation. Here, we create fission yeast strains retaining one histone H3 and H4 gene; the creation of these strains allows mutation of specific N-terminal tail residues and their role in centromeric silencing and chromosome stability to be investigated.Results: Reduction of H3/H4 gene dosage to one-third does not affect cell viability or heterochromatin formation. Mutation of lysines 9 or 14 or serine 10 within the amino terminus of histone H3 impairs centromere function, leading to defective chromosome segregation and Swi6 delocalization. Surprisingly, silent centromeric chromatin does not require the conserved lysine 8 and 16 residues of histone H4.Conclusions: To date, mutation of conserved N-terminal residues in endogenous histone genes has only been performed in budding yeast, which lacks the Clr4/Suvar39 histone methyltransferase and Swi6/HP1. We demonstrate the importance of conserved residues within the histone H3 N terminus for the maintenance of centromeric heterochromatin in fission yeast. In sharp contrast, mutation of two conserved lysines within the histone H4 tail has no impact on the integrity of centromeric heterochromatin. Our data highlight the striking divergence between the histone tail requirements for the fission yeast and budding yeast silencing pathways

Melatonin for rapid eye movement sleep behavior disorder in Parkinson's disease : a randomised controlled trial

Background Melatonin may reduce REM-sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD), though robust clinical trials are lacking. Objective To assess the efficacy of prolonged-release (PR) melatonin for RBD in PD. Methods Randomized, double-blind, placebo-controlled, parallel-group trial with an 8-week intervention and 4-week observation pre- and postintervention (ACTRN12613000648729). Thirty PD patients with rapid eye movement sleep behavior disorder were randomized to 4 mg of prolonged-release melatonin (Circadin) or matched placebo, ingested orally once-daily before bedtime. Primary outcome was the aggregate of rapid eye movement sleep behavior disorder incidents averaged over weeks 5 to 8 of treatment captured by a weekly diary. Data were included in a mixed-model analysis of variance (n = 15 per group). Results No differences between groups at the primary endpoint (3.4 events/week melatonin vs. 3.6 placebo; difference, 0.2; 95% confidence interval = -3.2 to 3.6; P = 0.92). Adverse events included mild headaches, fatigue, and morning sleepiness (n = 4 melatonin; n = 5 placebo). Conclusion Prolonged-release melatonin 4 mg did not reduce rapid eye movement sleep behavior disorder in PD. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Is Metabolic Rate Increased in Insomnia Disorder? A Systematic Review

Background: Insomnia disorder is a highly prevalent health condition, affecting ~10–15% of the adult population worldwide. A central feature of insomnia is hyperarousal characterized as persistent and increased somatic, cognitive and cortical stimulation. Hyperarousal leads to a state of conditioned arousal that disrupts both sleep and daytime function. Research studies have shown increases in body temperature, heart rate, electroencephalographic activity, catecholamines, and oxygen consumption as a measure of metabolic rate. These findings provide evidence of increased physiological activation in insomnia however results are not consistent. The aim of the systematic review was to determine if metabolic rate in patients with insomnia is increased in keeping with the hyperarousal hypothesis.Methods: We searched Pubmed, Web of Science, CINAHL, PsycINFO, EMBASE, and Scopus databases for observational and interventional studies that have measured metabolic rate in insomnia. Study characteristics were extracted and summarized and a risk of bias was performed for each of the studies.Results: Two reviewers screened 963 abstracts with 35 articles of interest for full-text review. Four articles evaluating 75 participants were included in this systematic review. Two studies showed increased oxygen consumption across 24 h in insomnia patients compared with good-sleeping controls. One study which measured oxygen consumption at only a single timepoint showed no difference between insomnia patients and good-sleeping controls. A further study evaluating the effect of lorazepam on oxygen consumption in patients with chronic insomnia showed that lorazepam reduced metabolic rate during the night time only.Conclusions: These findings show that metabolic rate appears to be increased across 24 h in line with the hyperarousal model of insomnia. However, these increases in metabolic rate in insomnia were minor compared to good-sleeping controls and the clinical significance is unclear. Larger, methodologically robust studies are required to confirm these findings and the effect of any increase in metabolic rate on sleep-wake disturbances or pathophysiology