Clinical features, plasma neurotransmitter levels and plasma neurohormone levels among patients with early-stage Parkinson's disease with sleep disorders

Cell Commun Signal. 2025 Mar 18;23(1):144. doi: 10.1186/s12964-025-02153-8.

Abstract

Background: Sleep disorders occur frequently among patients with Parkinson's disease (PD). Neurotransmitters and neurosteroids are known to be involved in various neurophysiological processes, including sleep development. We aimed to assess the associations of peripheral neurotransmitter and neurosteroid levels with various sleep disorders in early-stage PD.

Methods: Fifty-nine patients with early-stage PD and 30 healthy controls were enrolled. Demographic and clinical data were collected, and sleep conditions were comprehensively assessed with clinical questionnaires and polysomnography. Blood samples were obtained from all participants at 1:00 AM and 9:00 AM. The concentrations of plasma neurotransmitters and neurohormones were detected via high-performance liquid chromatography tandem mass spectrometry.

Results: Sleep disorders were common nonmotor symptoms (81.4%) and coexisted in approximately half of the patients. Dysautonomia was significantly associated with the presence of multiple sleep disorders. RBD was associated with dysautonomia and was negatively correlated with the plasma melatonin concentration at 1:00 AM (r = - 0.40, p = 0.002) in early-stage PD patients. The RLS group had higher PSQI scores, and RLS was negatively associated with the 5-hydroxytryptamine levels (r = - 0.40, p = 0.002) at 1:00 AM and glutamine levels (r = - 0.39, p = 0.002) at 9:00 AM. SDB was associated with cognitive impairment, a greater body mass index, and lower plasma acetylcholine concentrations at 1:00 AM.

Conclusion: Combined sleep disturbances are common in early-stage PD. Dysautonomia is closely related to various sleep disorders, including RBD, EDS, and insomnia. Changes in peripheral neurotransmitter and neurohormone levels may be involved in the development of sleep disorders.

Keywords: Parkinson’s disease; Plasma neurotransmitter and neurohormone levels; Sleep disorders.

Plain language summary

Many people with Parkinson’s disease (PD) experience sleep problems. Chemicals in the body called neurotransmitters and neurosteroids play a role in sleep regulation. This study looked at how levels of these chemicals in the blood might be linked to sleep disorders in people with early-stage PD. We found that sleep problems were very common in PD patients (81.4%), and about half had multiple sleep issues. Dysautonomia was linked to multiple sleep disorders. REM sleep behavior disorder (RBD) was linked to dysautonomia and lower levels of melatonin at 1:00 AM, restless legs syndrome (RLS) was associated with poorer sleep quality and lower levels of serotonin and glutamine at different times. Sleep-disordered breathing (SDB) was linked to memory problems, higher body weight, and lower levels of acetylcholine at 1:00 AM. Understanding these links could help improve sleep treatments for PD patients.

MeSH terms

  • Aged
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurotransmitter Agents* / blood
  • Parkinson Disease* / blood
  • Parkinson Disease* / complications
  • Sleep Wake Disorders* / blood
  • Sleep Wake Disorders* / complications

Substances

  • Neurotransmitter Agents