title: Decline of CSF orexin (hypocretin) levels in Prader-Willi syndrome.
abstract: Prader-Willi syndrome is a congenital neurodevelopmental disorder resulting from deletion of the paternal copies of genes within the chromosome region 15q11-q13. Patients with Prader-Willi syndrome often exhibit excessive daytime sleepiness, excessive appetite, and obesity. As is the case in narcolepsy, orexin (hypocretin) may be responsible for these symptoms. However, reports showing cerebrospinal fluid orexin levels in Prader-Willi syndrome patients have been limited. The aim of this study was to examine the relationship between the characteristic symptoms of Prader-Willi syndrome and cerebrospinal fluid orexin levels. We clinically identified 14 Prader-Willi syndrome patients and examined their cerebrospinal fluid orexin levels. A total of 12 patients with a 15q11-q13 deletion and two patients with maternal uniparental disomy of chromosome 15 were identified. A total of 37 narcoleptic patients and 14 idiopathic hypersomnia patients were recruited for comparison. Cerebrospinal fluid orexin levels (median [25-75 percentiles]) in the 14 Prader-Willi syndrome patients were intermediate (192 [161-234.5] pg/ml), higher than in the narcoleptic patients, but lower than in the idiopathic hypersomnia patients. Body mass index of the Prader-Willi syndrome patients was higher than in the narcoleptic and idiopathic hypersomnia patients. There was also a negative correlation between Epworth sleepiness scale scores and orexin levels in Prader-Willi syndrome patients. Decreased cerebrospinal fluid orexin levels in Prader-Willi syndrome may play an important role in severity of obesity and excessive daytime sleepiness.
authors.affiliation: Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Omokawa
authors.affiliation: Department of Pediatrics, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Ayabe
authors.affiliation: Department of Pediatrics, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Imanishi
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Omokawa
authors.affiliation: Sleep and Circadian Neurobiology Laboratory, Stanford University School of Medicine, Palo Alto, California.
authors.forename: Seiji
authors.initials: S
authors.lastname: Nishino
authors.affiliation: Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Sagawa
authors.affiliation: Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan.|International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan.|International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanbayashi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005260:Female; D006801:Humans; D020177:Idiopathic Hypersomnia / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D009290:Narcolepsy / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000503:physiopathology; D009765:Obesity / Q000134:cerebrospinal fluid / Q000235:genetics / Q000503:physiopathology; D000068797:Orexins / Q000134:cerebrospinal fluid* / Q000235:genetics; D011218:Prader-Willi Syndrome / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000503:physiopathology
chemical_list: D000068797:Orexins
keywords: Prader-Willi syndrome; hypersomnia; narcolepsy; obesity; orexin