Disturbances in melatonin secretion and circadian sleep-wake regulation in Parkinson disease

Sleep Med. 2014 Mar;15(3):342-7. doi: 10.1016/j.sleep.2013.10.016. Epub 2014 Jan 21.


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.

Keywords: Actigraphy; Circadian; Dopamine; Melatonin; Parkinson disease; Sleep disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actigraphy
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / therapeutic use
  • Case-Control Studies
  • Chronobiology Disorders / chemically induced
  • Chronobiology Disorders / etiology*
  • Chronobiology Disorders / physiopathology
  • Female
  • Humans
  • Levodopa / adverse effects
  • Levodopa / therapeutic use
  • Male
  • Melatonin / analysis
  • Melatonin / metabolism*
  • Middle Aged
  • Parkinson Disease / complications*
  • Parkinson Disease / drug therapy
  • Parkinson Disease / physiopathology
  • Polysomnography
  • Saliva / chemistry


  • Antiparkinson Agents
  • Levodopa
  • Melatonin