title: The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy.
abstract: Narcolepsy with cataplexy is a sleep dysregulation disorder with alterations of REM sleep, i.e., sleep onset REM periods and REM sleep instability. Deficient orexin-A (hypocretin-1) signaling is assumed to be a major cause of narcolepsy with cataplexy. In this study we investigated fourteen subjects with narcolepsy with cataplexy in a within-subject, random-order crossover, placebo-controlled design. Patients received double-blinded intranasal orexin-A (435 nmol) or sterile water (placebo) in the morning. Administration was preceded by an adaptation night and followed by a modified maintenance of wakefulness test, attention testing and a second full night of polysomnographic recording. We found comparable sleep behavior during the adaptation nights between both conditions. After orexin-A administration patients had less wake-REM sleep transitions and a decreased REM sleep duration. In the subsequent night, patients showed an increased N2 duration. In the test of divided attention, patients had fewer false reactions after orexin-A administration. Our results support orexin-A to be a REM sleep stabilizing factor and provide functional signs for effects of orexin-A on sleep alterations and attention in narcolepsy with cataplexy.
authors.affiliation: Centre for Sleep Medicine, Department of Psychiatry and Psychotherapy, Christian-Albrechts University Kiel, Niemannsweg 147, Kiel D-24105, Germany. Electronic address: s.weinhold@zip-kiel.de.
authors.forename: Sara Lena
authors.initials: SL
authors.lastname: Weinhold
authors.affiliation: Centre for Sleep Medicine, Department of Psychiatry and Psychotherapy, Christian-Albrechts University Kiel, Niemannsweg 147, Kiel D-24105, Germany.
authors.forename: Mareen
authors.initials: M
authors.lastname: Seeck-Hirschner
authors.affiliation: Centre for Sleep Medicine, Department of Psychiatry and Psychotherapy, Christian-Albrechts University Kiel, Niemannsweg 147, Kiel D-24105, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Nowak
authors.affiliation: Department of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen D-72076, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Hallschmid
authors.affiliation: Centre for Sleep Medicine, Department of Psychiatry and Psychotherapy, Christian-Albrechts University Kiel, Niemannsweg 147, Kiel D-24105, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Göder
authors.affiliation: Centre for Sleep Medicine, Department of Psychiatry and Psychotherapy, Christian-Albrechts University Kiel, Niemannsweg 147, Kiel D-24105, Germany.
authors.forename: Paul Christian
authors.initials: PC
authors.lastname: Baier
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D001288:Attention / Q000187:drug effects*; D002385:Cataplexy / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009290:Narcolepsy / Q000188:drug therapy*; D009479:Neuropeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D000068797:Orexins; D012895:Sleep, REM / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects*
chemical_list: C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins
keywords: Attention; Hypocretin-1; Intranasal; Narcolepsy; Orexin-A; Sleep stability