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

• Published in: Parkinsonism & related disorders Vol. 91; pp. 48 - 54
• Main Authors: Timmers, Elze R., van Faassen, Martijn, Smit, Marenka, Kuiper, Anouk, Hof, Ingrid H., Kema, Ido P., Tijssen, Marina A.J., Niezen-Koning, Klary E., de Koning, Tom J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2021
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cervical dystonia; Child; Clinical Medicine; Dopa-responsive dystonia; Dopamine - blood; Dystonic Disorders - blood; Dystonic Disorders - drug therapy; Female; Humans; Klinisk medicin; Levodopa - blood; Levodopa - therapeutic use; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; Monoamine neurotransmitters; Motor Activity - drug effects; Motor Activity - physiology; Myoclonus-dystonia; Neurologi; Neurology; Non-motor symptoms; Serotonin - blood; Torticollis - blood; Torticollis - drug therapy; Young Adult; Dopa-responsive dystonia; Myoclonus-dystonia; Non-motor symptoms; Monoamine neurotransmitters; Cervical dystonia
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2021.08.019

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. 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. 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). 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. •Dystonia patients have changes in dopamine and serotonin metabolites in plasma.•Differences in metabolites of dopamine and serotonin dystonia subtype specific.•Low levels of levodopa are associated with motor and non-motor symptoms.