title: Higher plasma orexin A levels in children with Prader-Willi syndrome compared with healthy unrelated sibling controls.
abstract: Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder associated with maladaptive social behavior, hyperphagia, and morbid obesity. Orexin A is a hypothalamic neuropeptide important as a homeostatic regulator of feeding behavior and in energy metabolism through actions in the lateral hypothalamus. Dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia seen in PWS and we sought to assess orexin A levels in PWS relative to controls children. Morning fasting plasma orexin A levels were analyzed in 23 children (aged 5-11 years) with genetically confirmed PWS and 18 age and gender matched healthy unrelated siblings without PWS. Multiplex immune assays utilized the Milliplex Human Neuropeptide Magnetic panel and the Luminex platform. Natural log-transformed orexin A data were analyzed using general linear model adjusting for diagnosis, gender, age, total body fat and body mass index (BMI). Plasma orexin A levels were significantly higher (P < 0.006) in children with PWS (average ±SD = 1028 pg/ml ± 358) compared with unrelated siblings (average ±SD = 609 pg/ml ± 351; P < 0.001). Orexin A levels correlated with age in females and were significantly elevated in PWS even after these effects were controlled. These findings support the hypothesis that dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia in PWS. Further studies are warranted to better understand the complex relationship between orexin A levels and the problematic behaviors consistently found in individuals with PWS. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Manzardo
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Lisa
authors.initials: L
authors.lastname: Johnson
authors.affiliation: Department of Pediatrics, University of Florida Medical Center, Gainesville, Florida.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Miller
authors.affiliation: Department of Pediatrics, University of Florida Medical Center, Gainesville, Florida.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Driscoll
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, Kansas.|Department of Pediatrics, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Merlin G
authors.initials: MG
authors.lastname: Butler
mesh_terms: D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15; D005260:Female; D006801:Humans; D008297:Male; D000068797:Orexins / Q000097:blood*; D011218:Prader-Willi Syndrome / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D035781:Siblings
chemical_list: D015415:Biomarkers; D000068797:Orexins
keywords: Prader-Willi syndrome; abnormal behavior; hyperphagia; neuropeptide; orexin A