Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients
(2021) In Parkinsonism and Related Disorders 91. p.48-54- Abstract
Introduction: In dystonia, dopaminergic alterations are considered to be responsible for the motor symptoms. Recent attention for the highly prevalent non-motor symptoms suggest also a role for serotonin in the pathophysiology. In this study we investigated the dopaminergic, serotonergic and noradrenergic metabolism in blood samples of dystonia patients and its relation with (non-)motor manifestations. Methods: Concentrations of metabolites of dopaminergic, serotonergic and noradrenergic pathways were measured in platelet-rich plasma in 41 myoclonus-dystonia (M-D), 25 dopa-responsive dystonia (DRD), 50 cervical dystonia (CD) patients and 55 healthy individuals. (Non-)motor symptoms were assessed using validated instruments, and... (More)
Introduction: In dystonia, dopaminergic alterations are considered to be responsible for the motor symptoms. Recent attention for the highly prevalent non-motor symptoms suggest also a role for serotonin in the pathophysiology. In this study we investigated the dopaminergic, serotonergic and noradrenergic metabolism in blood samples of dystonia patients and its relation with (non-)motor manifestations. Methods: Concentrations of metabolites of dopaminergic, serotonergic and noradrenergic pathways were measured in platelet-rich plasma in 41 myoclonus-dystonia (M-D), 25 dopa-responsive dystonia (DRD), 50 cervical dystonia (CD) patients and 55 healthy individuals. (Non-)motor symptoms were assessed using validated instruments, and correlated with concentrations of metabolites. Results: A significantly higher concentration of 3-methoxytyramine (0.03 vs. 0.02 nmol/L, p < 0.01), a metabolite of dopamine, and a reduced concentration of tryptophan (50 vs. 53 μmol/L, p = 0.03), the precursor of serotonin was found in dystonia patients compared to controls. The dopamine/levodopa ratio was higher in CD patients compared to other dystonia groups (p < 0.01). Surprisingly, relatively high concentrations of levodopa were found in the untreated DRD patients. Low concentrations of levodopa were associated with severity of dystonia (rs = −0.3, p < 0.01), depression (rs = −0.3, p < 0.01) and fatigue (rs = −0.2, p = 0.04). Conclusion: This study shows alterations in the dopaminergic and serotonergic metabolism of patients with dystonia, with dystonia subtype specific changes. Low concentrations of levodopa, but not of serotonergic metabolites, were associated with both motor and non-motor symptoms. Further insight into the dopaminergic and serotonergic systems in dystonia with a special attention to the kinetics of enzymes involved in these pathways, might lead to better treatment options.
(Less)
- author
- Timmers, Elze R. ; van Faassen, Martijn ; Smit, Marenka ; Kuiper, Anouk ; Hof, Ingrid H. ; Kema, Ido P. ; Tijssen, Marina A.J. ; Niezen-Koning, Klary E. and de Koning, Tom J. LU
- organization
- publishing date
- 2021-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cervical dystonia, Dopa-responsive dystonia, Monoamine neurotransmitters, Myoclonus-dystonia, Non-motor symptoms
- in
- Parkinsonism and Related Disorders
- volume
- 91
- pages
- 48 - 54
- publisher
- Elsevier
- external identifiers
-
- scopus:85114189078
- pmid:34482194
- ISSN
- 1353-8020
- DOI
- 10.1016/j.parkreldis.2021.08.019
- language
- English
- LU publication?
- yes
- additional info
- Funding Information: This study was funded by the Dystonia Medical Research Foundation (DMRF) and Dystonie Wetenschapsfonds . The funding agencies had no involvement in study design, collection, analysis and interpretation of data or writing of the report. ET received funding from Junior Scientific Masterclass from the University of Groningen , University Medical Center Groningen . All other authors report no disclosures. Publisher Copyright: © 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
- id
- e742d73d-5148-45be-a693-9e9174bd193b
- date added to LUP
- 2021-09-20 08:26:18
- date last changed
- 2024-06-15 16:32:00
@article{e742d73d-5148-45be-a693-9e9174bd193b,
abstract = {{<p>Introduction: In dystonia, dopaminergic alterations are considered to be responsible for the motor symptoms. Recent attention for the highly prevalent non-motor symptoms suggest also a role for serotonin in the pathophysiology. In this study we investigated the dopaminergic, serotonergic and noradrenergic metabolism in blood samples of dystonia patients and its relation with (non-)motor manifestations. Methods: Concentrations of metabolites of dopaminergic, serotonergic and noradrenergic pathways were measured in platelet-rich plasma in 41 myoclonus-dystonia (M-D), 25 dopa-responsive dystonia (DRD), 50 cervical dystonia (CD) patients and 55 healthy individuals. (Non-)motor symptoms were assessed using validated instruments, and correlated with concentrations of metabolites. Results: A significantly higher concentration of 3-methoxytyramine (0.03 vs. 0.02 nmol/L, p < 0.01), a metabolite of dopamine, and a reduced concentration of tryptophan (50 vs. 53 μmol/L, p = 0.03), the precursor of serotonin was found in dystonia patients compared to controls. The dopamine/levodopa ratio was higher in CD patients compared to other dystonia groups (p < 0.01). Surprisingly, relatively high concentrations of levodopa were found in the untreated DRD patients. Low concentrations of levodopa were associated with severity of dystonia (r<sub>s</sub> = −0.3, p < 0.01), depression (r<sub>s</sub> = −0.3, p < 0.01) and fatigue (r<sub>s</sub> = −0.2, p = 0.04). Conclusion: This study shows alterations in the dopaminergic and serotonergic metabolism of patients with dystonia, with dystonia subtype specific changes. Low concentrations of levodopa, but not of serotonergic metabolites, were associated with both motor and non-motor symptoms. Further insight into the dopaminergic and serotonergic systems in dystonia with a special attention to the kinetics of enzymes involved in these pathways, might lead to better treatment options.</p>}},
author = {{Timmers, Elze R. and van Faassen, Martijn and Smit, Marenka and Kuiper, Anouk and Hof, Ingrid H. and Kema, Ido P. and Tijssen, Marina A.J. and Niezen-Koning, Klary E. and de Koning, Tom J.}},
issn = {{1353-8020}},
keywords = {{Cervical dystonia; Dopa-responsive dystonia; Monoamine neurotransmitters; Myoclonus-dystonia; Non-motor symptoms}},
language = {{eng}},
pages = {{48--54}},
publisher = {{Elsevier}},
series = {{Parkinsonism and Related Disorders}},
title = {{Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients}},
url = {{http://dx.doi.org/10.1016/j.parkreldis.2021.08.019}},
doi = {{10.1016/j.parkreldis.2021.08.019}},
volume = {{91}},
year = {{2021}},
}