title: Melatonin dysregulation, sleep disturbances and fatigue in multiple sclerosis.
abstract: BACKGROUND
  Sleep disruption and fatigue are common in Multiple Sclerosis (MS). Melatonin is one of the major regulators of sleep-wake cycle. The role of melatonin in MS-related sleep disturbances and fatigue as well as the interaction between melatonin and Interferon beta (IFN-β) treatment were the subject of this study.
  
  
  OBJECTIVE
  To assess the influence of IFN-β treatment on melatonin secretion, fatigue and sleep characteristics in patients with MS.
  
  
  METHODS
  13 MS patients and 12 healthy controls participated. Fatigue was evaluated using the Fatigue Impact Scale (FIS), sleep was assessed by actigraphy and day/night levels of 6-sulphatoxy-melatonin (6-SMT) in urine were determined using a highly specific ELISA assay.
  
  
  RESULTS
  Naïve MS patients demonstrated significantly decreased levels of 6-SMT and disrupted circadian regulation of its secretion, which were increased with IFN-β treatment, in association with improved fatigue. Sleep Efficiency was significantly lower in the MS group compared to controls.
  
  
  CONCLUSIONS
  Our findings suggest dysregulation of Melatonin secretion in MS, which may be influenced by IFN-β treatment. The results call for further characterization of the role of neuro-hormones such as melatonin in MS, and their cross-regulation with immune-mediators.
authors.affiliation: Division of Neuroimmunology & Multiple Sclerosis Center, Carmel Medical Center, Haifa, Israel.
authors.forename: Lena
authors.initials: L
authors.lastname: Melamud
authors.forename: Daniel
authors.initials: D
authors.lastname: Golan
authors.forename: Rafael
authors.initials: R
authors.lastname: Luboshitzky
authors.forename: Idit
authors.initials: I
authors.lastname: Lavi
authors.forename: Ariel
authors.initials: A
authors.lastname: Miller
mesh_terms: D000328:Adult; D002940:Circadian Rhythm / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005221:Fatigue / Q000209:etiology* / Q000378:metabolism* / Q000523:psychology; D005260:Female; D006801:Humans; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use; D008550:Melatonin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged; D009043:Motor Activity; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012893:Sleep Wake Disorders / Q000209:etiology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D000068576:Interferon beta-1b; C054513:6-sulfatoxymelatonin; D016899:Interferon-beta; D008550:Melatonin