Serotonergic system in vivo with [11C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients

• DOI: 10.1038/s41598-022-10067-5
• Publication Date: 2022-04-15T14:02:45Z
• Authors: Elze R. Timmers; Débora E. Peretti; Marenka Smit; Bauke M. de Jong; Rudi A. J. O. Die...; Anouk Kuiper; Tom J. de Koning; David Vállez García; Marina A. J. Tijssen
• Keywords: Science; Q; R; Dystonic Disorders/diagnostic imaging; 16. Peace & justice; Article; 3. Good health; Levodopa; 03 medical and health sciences; 0302 clinical medicine; Dystonic Disorders; Positron-Emission Tomography; Medicine; Humans; Guanosine Triphosphate; GTP Cyclohydrolase; GTP Cyclohydrolase/genetics

AbstractGTP-cyclohydrolase deficiency in dopa-responsive dystonia (DRD) patients impairs the biosynthesis of dopamine, but also of serotonin. The high prevalence of non-motor symptoms suggests involvement of the serotonergic pathway. Our study aimed to investigate the serotonergic system in vivo in the brain of`DRD patients and correlate this to (non-)motor symptoms. Dynamic [11C]DASB PET scans, a marker of serotonin transporter availability, were performed. Ten DRD, 14 cervical dystonia patients and 12 controls were included. Univariate- and network-analysis did not show differences in binding between DRD patients compared to controls. Sleep disturbances were correlated with binding in the dorsal raphe nucleus (all participants: rs = 0.45, p = 0.04; patients: rs = 0.64, p = 0.05) and participants with a psychiatric disorder had a lower binding in the hippocampus (all participants: p = 0.00; patients: p = 0.06). Post-hoc analysis with correction for psychiatric co-morbidity showed a significant difference in binding in the hippocampus between DRD patients and controls (p = 0.00). This suggests that psychiatric symptoms might mask the altered serotonergic metabolism in DRD patients, but definite conclusions are difficult as psychiatry is considered part of the phenotype. We hypothesize that an imbalance between different neurotransmitter systems is responsible for the non-motor symptoms, and further research investigating multiple neurotransmitters and psychiatry in DRD is necessary.