title: Disturbances in melatonin secretion and circadian sleep-wake regulation in Parkinson disease.
abstract: OBJECTIVE
  Using salivary dim light melatonin onset (DLMO) and actigraphy, our study sought to determine if Parkinson disease (PD) patients demonstrate circadian disturbance compared to healthy controls. Additionally, our study investigated if circadian disturbances represent a disease-related process or may be attributed to dopaminergic therapy.
  
  
  METHODS
  Twenty-nine patients with PD were divided into unmedicated and medicated groups and were compared to 27 healthy controls. All participants underwent neurologic assessment and 14 days of actigraphy to establish habitual sleep-onset time (HSO). DLMO time and area under the melatonin curve (AUC) were calculated from salivary melatonin sampling. The phase angle of entrainment was calculated by subtracting DLMO from HSO. Overnight polysomnography (PSG) was performed to determine sleep architecture.
  
  
  RESULTS
  DLMO and HSO were not different across the groups. However, the phase angle of entrainment was more than twice as long in the medicated PD group compared to the unmedicated PD group (U = 35.5; P = .002) and was more than 50% longer than controls (U = 130.0; P = .021). The medicated PD group showed more than double the melatonin AUC compared to the unmedicated group (U = 31; P = 0.001) and controls (U = 87; P = .001). There was no difference in these measures comparing unmedicated PD and controls.
  
  
  CONCLUSIONS
  In PD dopaminergic treatment profoundly increases the secretion of melatonin. Our study reported no difference in circadian phase and HSO between groups. However, PD patients treated with dopaminergic therapy unexpectedly showed a delayed sleep onset relative to DLMO, suggesting dopaminergic therapy in PD results in an uncoupling of circadian and sleep regulation.
authors: Parkinson's Disease Clinic, Brain and Mind Research Institute, The University of Sydney, NSW, Australia.
authors: S J
authors: SJ
authors: Bolitho
authors: Healthy Brain Ageing Clinic, Ageing Brain Centre, Brain and Mind Research Institute, University of Sydney, NSW, Australia.
authors: S L
authors: SL
authors: Naismith
authors: School of Psychology and Psychiatry, Monash University, Vic, Australia.
authors: S M W
authors: SM
authors: Rajaratnam
authors: Woolcock Institute of Medical Research, University of Sydney, NSW, Australia.
authors: R R
authors: RR
authors: Grunstein
authors: Ageing and Neurodegeneration, Neuroscience Research Australia, NSW, Australia.
authors: J R
authors: JR
authors: Hodges
authors: Healthy Brain Ageing Clinic, Ageing Brain Centre, Brain and Mind Research Institute, University of Sydney, NSW, Australia.
authors: Z
authors: Z
authors: Terpening
authors: Chronobiology and Sleep, Institute for Health and Social Science Research, Central Queensland University, Qld, Australia.
authors: N
authors: N
authors: Rogers
authors: Parkinson's Disease Clinic, Brain and Mind Research Institute, The University of Sydney, NSW, Australia. Electronic address: simonl@med.usyd.edu.au.
authors: S J G
authors: SJ
authors: Lewis
mesh_terms: D056044:Actigraphy; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use; D016022:Case-Control Studies; D021081:Chronobiology Disorders / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008550:Melatonin / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D017286:Polysomnography; D012463:Saliva / Q000737:chemistry
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D008550:Melatonin
keywords: Actigraphy; Circadian; Dopamine; Melatonin; Parkinson disease; Sleep disorders