Session Time: 1:45pm-3:15pm
Location: Hall 3FG
Objective: To assess the non-displaceable binding potential (BPND) of the serotonin transporter (SERT) in dopa-responsive dystonia (DRD) patients and to determine if an altered BPND contributes to the pathophysiology of the motor and non-motor symptoms (NMS).
Background: GTP-cyclohydrolase deficiency in dopa-responsive dystonia (DRD) patients result in an impairment in the synthesis of monoamines such as dopamine and serotonin. In children with DRD decreased levels of serotonin metabolites in cerebrospinal fluid have been reported. It is hypothesized that an altered serotonergic metabolism contributes to the pathophysiology of dystonia and NMS, such as psychiatric co-morbidity.
Methods: We studied the BPND of SERT using [11C]DASB positron emission tomography (PET) imaging of the brain in 10 DRD patients and 12 matched controls. Motor symptoms and NMS were assessed with quantitative rating scales. Comparisons between groups were performed using Mann Whitney U test. In patients, correlations between BPND and clinical symptoms were calculated using Spearman’s Rho test.
Results: Preliminary analysis showed no significant differences in BPND between DRD patients and controls. Psychiatric symptoms were highly prevalent in the patient group and the presence of a psychiatric disorder was statistically significantly correlated with the BPND in the hippocampus (rs=0.85, p<0.01). Severity of anxiety was positively correlated with the BPND in the caudate nucleus (rs=0.66, p=0.04) and substantia nigra (rs=0.63, p=0.05). Severity of depression was correlated with the BPND in the globus pallidus (rs= 0.63, p=0.05). In all patients dystonia symptoms were well-controlled with levodopa treatment (mean BFMS score 7.4) and were not correlated with BPND in any of the brain regions.
Conclusions: In contrast to our initial hypothesis, our preliminary results show no differences in SERT binding in DRD patients compared to controls. Motor symptoms were not associated with SERT binding, this might be due to the levodopa treatment. However, NMS are highly prevalent in DRD patients and are correlated with an altered serotonergic metabolism in the brain. Based on this research we cannot state whether these alterations are part of the pathophysiology of DRD. Further research is necessary to investigate the underlying neurobiology of NMS in DRD.
To cite this abstract in AMA style:E. Timmers, D. Vállez García, A. Bartels, A. Kuiper, R. Dierckx, M. Smit, M. Tijssen. [11 C] DASB PET imaging in dopa-responsive dystonia patients: The role of serotonin in motor and non-motor symptoms [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/11-c-dasb-pet-imaging-in-dopa-responsive-dystonia-patients-the-role-of-serotonin-in-motor-and-non-motor-symptoms/. Accessed September 25, 2023.
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