Serotonergic system in vivo with [11C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients
Abstract 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...
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Nature Portfolio
2022-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-10067-5 |
| _version_ | 1818022506751066112 |
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| author | Elze R. Timmers Débora E. Peretti Marenka Smit Bauke M. de Jong Rudi A. J. O. Dierckx Anouk Kuiper Tom J. de Koning David Vállez García Marina A. J. Tijssen |
| author_facet | Elze R. Timmers Débora E. Peretti Marenka Smit Bauke M. de Jong Rudi A. J. O. Dierckx Anouk Kuiper Tom J. de Koning David Vállez García Marina A. J. Tijssen |
| author_sort | Elze R. Timmers |
| collection | DOAJ |
| description | Abstract 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 [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: r s = 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. |
| first_indexed | 2024-12-10T03:29:31Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-10T03:29:31Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dd3b0bff2a6c4eb5a4997a0bcdc1eef62022-12-22T02:03:52ZengNature PortfolioScientific Reports2045-23222022-04-011211910.1038/s41598-022-10067-5Serotonergic system in vivo with [11C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patientsElze R. Timmers0Débora E. Peretti1Marenka Smit2Bauke M. de Jong3Rudi A. J. O. Dierckx4Anouk Kuiper5Tom J. de Koning6David Vállez García7Marina A. J. Tijssen8Department of Neurology, University Medical Center Groningen, University of GroningenDepartment of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen (UMCG), University of GroningenDepartment of Neurology, University Medical Center Groningen, University of GroningenDepartment of Neurology, University Medical Center Groningen, University of GroningenDepartment of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen (UMCG), University of GroningenDepartment of Neurology, University Medical Center Groningen, University of GroningenExpertise Center Movement Disorders Groningen, University Medical Center Groningen (UMCG)Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen (UMCG), University of GroningenDepartment of Neurology, University Medical Center Groningen, University of GroningenAbstract 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 [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: r s = 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.https://doi.org/10.1038/s41598-022-10067-5 |
| spellingShingle | Elze R. Timmers Débora E. Peretti Marenka Smit Bauke M. de Jong Rudi A. J. O. Dierckx Anouk Kuiper Tom J. de Koning David Vállez García Marina A. J. Tijssen Serotonergic system in vivo with [11C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients Scientific Reports |
| title | Serotonergic system in vivo with [11C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients |
| title_full | Serotonergic system in vivo with [11C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients |
| title_fullStr | Serotonergic system in vivo with [11C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients |
| title_full_unstemmed | Serotonergic system in vivo with [11C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients |
| title_short | Serotonergic system in vivo with [11C]DASB PET scans in GTP-cyclohydrolase deficient dopa-responsive dystonia patients |
| title_sort | serotonergic system in vivo with 11c dasb pet scans in gtp cyclohydrolase deficient dopa responsive dystonia patients |
| url | https://doi.org/10.1038/s41598-022-10067-5 |
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