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

GTP-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 brai...

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Autores principales: Timmers, Elze R., Peretti, Débora E., Smit, Marenka, de Jong, Bauke M., Dierckx, Rudi A. J. O., Kuiper, Anouk, de Koning, Tom J., Vállez García, David, Tijssen, Marina A. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9012759/
https://www.ncbi.nlm.nih.gov/pubmed/35428769
http://dx.doi.org/10.1038/s41598-022-10067-5
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author Timmers, Elze R.
Peretti, Débora E.
Smit, Marenka
de Jong, Bauke M.
Dierckx, Rudi A. J. O.
Kuiper, Anouk
de Koning, Tom J.
Vállez García, David
Tijssen, Marina A. J.
author_facet Timmers, Elze R.
Peretti, Débora E.
Smit, Marenka
de Jong, Bauke M.
Dierckx, Rudi A. J. O.
Kuiper, Anouk
de Koning, Tom J.
Vállez García, David
Tijssen, Marina A. J.
author_sort Timmers, Elze R.
collection PubMed
description GTP-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 [(11)C]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: r(s) = 0.45, p = 0.04; patients: r(s) = 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.
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spelling pubmed-90127592022-04-18 Serotonergic system in vivo with [(11)C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients Timmers, Elze R. Peretti, Débora E. Smit, Marenka de Jong, Bauke M. Dierckx, Rudi A. J. O. Kuiper, Anouk de Koning, Tom J. Vállez García, David Tijssen, Marina A. J. Sci Rep Article GTP-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 [(11)C]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: r(s) = 0.45, p = 0.04; patients: r(s) = 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. Nature Publishing Group UK 2022-04-15 /pmc/articles/PMC9012759/ /pubmed/35428769 http://dx.doi.org/10.1038/s41598-022-10067-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Timmers, Elze R.
Peretti, Débora E.
Smit, Marenka
de Jong, Bauke M.
Dierckx, Rudi A. J. O.
Kuiper, Anouk
de Koning, Tom J.
Vállez García, David
Tijssen, Marina A. J.
Serotonergic system in vivo with [(11)C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients
title Serotonergic system in vivo with [(11)C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients
title_full Serotonergic system in vivo with [(11)C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients
title_fullStr Serotonergic system in vivo with [(11)C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients
title_full_unstemmed Serotonergic system in vivo with [(11)C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients
title_short Serotonergic system in vivo with [(11)C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients
title_sort serotonergic system in vivo with [(11)c]dasb pet scans in gtp-cyclohydrolase deficient dopa-responsive dystonia patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9012759/
https://www.ncbi.nlm.nih.gov/pubmed/35428769
http://dx.doi.org/10.1038/s41598-022-10067-5
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