title: Hypothalamic volume loss is associated with reduced melatonin output in Parkinson's disease.
abstract: Recent studies have suggested that melatonin-a hormone produced by the pineal gland under circadian control-contributes to PD-related sleep dysfunction. We hypothesized that degenerative changes to the neural structures controlling pineal function (especially the suprachiasmatic nuclei of the anterior hypothalamus) may be responsible for reduced melatonin output in these patients. We compared hypothalamic volumes in PD patients with matched controls and determined whether volume loss correlated with reduced melatonin output in the PD group.
  
  
  
  A total of 12 PD patients and 12 matched controls underwent magnetic resonance imaging to determine hypothalamic volume. In addition, PD patients underwent 24-hour blood sampling in a controlled environment to determine serum melatonin concentrations using enzyme-linked immunosorbent assays.
  
  
  
  PD patients had significantly reduced hypothalamic gray matter volume when compared with matched controls. Melatonin levels were significantly associated with hypothalamic gray matter volume and disease severity in PD patients.
  
  
  
  Melatonin levels are associated with hypothalamic gray matter volume loss and disease severity in PD patients. This provides anatomical and physiological support for an intrinsic sleep and circadian phenotype in PD. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
authors.affiliation: John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
authors.forename: David P
authors.initials: DP
authors.lastname: Breen
authors.affiliation: John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Nombela
authors.affiliation: John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
authors.forename: Romina
authors.initials: R
authors.lastname: Vuono
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: P Simon
authors.initials: PS
authors.lastname: Jones
authors.affiliation: John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Fisher
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Burn
authors.affiliation: Division of Neurology, Imperial College, London, UK.|Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.affiliation: Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Akhilesh B
authors.initials: AB
authors.lastname: Reddy
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.|Medical Research Council Cognition and Brain Sciences Unit, Cambridge, UK.
authors.forename: James B
authors.initials: JB
authors.lastname: Rowe
authors.affiliation: John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Barker
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000000981:diagnostic imaging / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008550:Melatonin / Q000097:blood*; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D008550:Melatonin
keywords: Parkinson's; circadian; hypothalamus; melatonin; suprachiasmatic nucleus