![]() SCGE knockout mice show all the signs of dystonia, from jerks to depression-like behavior. In an animal model for myoclonus dystonia, an inherited form of dystonia caused by a mutation in the epsilon-sarcoglycan gene (SCGE) the hypothesis of a dysbalanced dopamine-serotonin system has been confirmed. Furthermore, dopaminergic neurons contain serotonin receptors, and serotonergic neurons contain dopamine receptors. In a rat study, long-term treatment with SSRIs led to a significant reduction of tyrosine hydroxylase, an important enzyme in the biosynthesis of dopamine, in the substantia nigra and striatum. There are strong clues that the brain serotonin and dopamine systems are closely interrelated. In addition, the role of serotonin in myoclonus pathophysiology gained more attention lately, and approximately 50% of CD patients have myoclonus (jerks) or tremor of the head. In the rare genetic syndrome of 5-HIAA deficiency, serotonin levels are low in the brain and patients suffer from dystonia. Furthermore, studies in patients with dopa-responsive dystonia and idiopathic adult-onset dystonia found decreased levels of serotonin metabolites, mainly 5-hydroxyindoleacetic acid (5-HIAA), in cerebrospinal fluid. There have been many case reports of drug-induced dystonia after the use of selective serotonin reuptake inhibitors (SSRIs). The role of serotonin in dystonia has not been studied with imaging or postmortem, but there are strong indications that alterations of the serotonergic system may indeed play a role. In line with this, postmortem studies in patients with major depressive disorder found reduced expression of SERTs in several brain regions including the midbrain. Reduced SERT binding in depression is hypothesized to reflect decreased expression of SERTs. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging studies in patients with major depression mostly showed reduced serotonin transporter (SERT) binding. Psychiatric symptoms, mainly depressive symptoms and anxiety, are very common in patients with dystonia with an estimated lifetime prevalence between 40 and 70% and are thought to be part of the dystonia phenotype. We also showed a significant relationship between striatal DAT binding and jerks/tremor of the head, which is a common symptom in CD, and a significant and negative relationship between both striatal DAT and D2/3 receptor binding and depressive symptoms. We recently showed normal striatal DAT binding but decreased D2/3 receptor binding in CD. Previous imaging studies in different types of dystonia have mostly shown normal radiotracer binding to striatal dopamine transporters (DAT) and normal or decreased binding to striatal dopamine D 2/3 receptors (D2/3 receptors). Dystonia has commonly been assumed to be a disorder of the dopaminergic system. Idiopathic cervical dystonia (CD dystonia of the neck) is the most common form of dystonia. The balance between extrastriatal SERT and striatal DAT binding is different in CD with and without jerks.ĭystonia is a syndrome characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. ConclusionĬD patients with psychiatric symptoms have lower SERT binding in the midbrain/diencephalon, while dystonia and jerks appear unrelated to SERT binding. There was a significant positive correlation between extrastriatal SERT and striatal DAT BP ND in CD patients with jerks, but not in patients without jerks. There was no correlation between SERT binding and dystonia, jerks, or anxiety. There was a clear trend towards reduced SERT BP ND in CD patients with psychiatric symptoms compared to those without ( p = 0.05). The specific to non-specific binding ratio (binding potential BP ND) to SERT was the main outcome measure. In 23 CD patients and 14 healthy controls, SERT binding in the diencephalon/midbrain was assessed using FP-CIT SPECT, with a brain-dedicated system. The balance between SERT and DAT binding can be altered in different CD phenotypes. We hypothesized that CD is associated with reduced serotonin transporter (SERT) binding, more specific that SERT binding is lower in CD patients with psychiatric symptoms and/or jerks/tremor compared to those without, and to controls. As serotonin is involved in the pathophysiology of psychiatric symptoms and jerks, we expected an altered serotoninergic system in CD. ![]() Serotonergic and dopaminergic systems are closely related. The dopamine transporter (DAT) binding is related with both depressive symptoms and jerks/tremor in CD. Cervical dystonia (CD) is often accompanied by depressive symptoms, anxiety, and jerks/tremor.
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