Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients

Elze R Timmers; Martijn van Faassen; Marenka Smit; Anouk Kuiper; Ingrid H Hof; Ido P Kema; Marina A J Tijssen; Klary E Niezen-Koning; Tom J de Koning

doi:10.1016/j.parkreldis.2021.08.019

Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients

Parkinsonism Relat Disord. 2021 Oct:91:48-54. doi: 10.1016/j.parkreldis.2021.08.019. Epub 2021 Sep 2.

Authors

Elze R Timmers¹, Martijn van Faassen², Marenka Smit³, Anouk Kuiper⁴, Ingrid H Hof⁵, Ido P Kema⁶, Marina A J Tijssen⁷, Klary E Niezen-Koning⁸, Tom J de Koning⁹

Affiliations

¹ Department of Neurology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands; Expertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG), PO Box 30.001, 9700 RB, Groningen, the Netherlands. Electronic address: e.r.timmers@umcg.nl.
² Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands. Electronic address: h.j.r.van.faassen@umcg.nl.
³ Department of Neurology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands; Expertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG), PO Box 30.001, 9700 RB, Groningen, the Netherlands. Electronic address: m.smit.03@umcg.nl.
⁴ Department of Neurology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands; Expertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG), PO Box 30.001, 9700 RB, Groningen, the Netherlands. Electronic address: anouk.kuiper@radboudumc.nl.
⁵ Laboratory of Metabolic Diseases, Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands. Electronic address: i.h.van.veen@umcg.nl.
⁶ Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands. Electronic address: i.p.kema@umcg.nl.
⁷ Department of Neurology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands; Expertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG), PO Box 30.001, 9700 RB, Groningen, the Netherlands. Electronic address: m.a.de.koning-tijssen@umcg.nl.
⁸ Expertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG), PO Box 30.001, 9700 RB, Groningen, the Netherlands; Laboratory of Metabolic Diseases, Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands. Electronic address: k.e.niezen-koning@umcg.nl.
⁹ Expertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG), PO Box 30.001, 9700 RB, Groningen, the Netherlands; Department of Clinical Sciences, Lund University, Box 117, 221 00, Lund, Sweden. Electronic address: t.j.de.koning@umcg.nl.

PMID: 34482194
DOI: 10.1016/j.parkreldis.2021.08.019

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 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_s = -0.3, p < 0.01), depression (r_s = -0.3, p < 0.01) and fatigue (r_s = -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.

Keywords: Cervical dystonia; Dopa-responsive dystonia; Monoamine neurotransmitters; Myoclonus-dystonia; Non-motor symptoms.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Case-Control Studies
Child
Dopamine / blood*
Dystonic Disorders / blood*
Dystonic Disorders / drug therapy
Female
Humans
Levodopa / blood*
Levodopa / therapeutic use
Male
Middle Aged
Motor Activity / drug effects
Motor Activity / physiology
Serotonin / blood*
Torticollis / blood*
Torticollis / drug therapy
Young Adult

Substances

Serotonin
Levodopa
Dopamine

Supplementary concepts

Dystonia, Dopa-responsive
Myoclonic dystonia