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

Abstract

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.

Cognitive and Neuropsychiatric Impairment in Dystonia

“…Abnormalities in serotonin neurotransmission were also observed in a small cohort of those diagnosed with DRD (n = 10), demonstrating a relationship between psychiatric symptoms and reduced hippocampal ligand binding [32]. Dopamine and its metabolites have also been implicated in dystonic symptoms with elevated levels of dopamine metabolites and lower levels of tryptophan (serotonin precursor) reported in cervical dystonia, myoclonus dystonia, and DRD compared to controls, while lower levels of levodopa have been associated with depression and more severe motor symptoms in dystonia [33]. A cross-sectional cohort study of those with DRD with and without GCH1 mutations also found the GCH1 mutation-positive cohort to report lower rates of self-satisfaction and higher levels of major depressive episodes prior to prescription of L-Dopa [34].…”

The use of sertraline to treat an adolescent of dystonia comorbid with major depressive disorder with psychotic features

“…Nevertheless, psychiatric symptoms may precede the onset of motor signs, 14 and associations were reported between dystonia‐related genes and psychiatric disorders, 15 suggesting these psychiatric comorbidities are primary and intrinsic to the neurobiology of dystonia. Dystonia is assumed to be a disorder of the dopaminergic system, and low L‐dopa concentrations have been linked to dystonia, fatigue, and depression 16 . Lower striatal DAT and dopamine D 2/3 receptor binding potentials were found in cervical dystonia patients with depression compared to those without 17 .…”

Methylation of the serotonin reuptake transporter gene and non-motor symptoms in dystonia patients

“…Also in dystonia, alterations in the serotonergic system are suggested. Low levels of the main metabolite of serotonin, 5-hydroxyindoleacetic acid, in the cerebrospinal fluid are described in several subtypes of dystonia, and in a previous study we found low levels of tryptophan, the precursor of serotonin, in blood samples of dystonia patients [ 5 , 6 ].…”