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Neuropsychiatric and sleep study in autosomal dominant dopa-responsive dystonia

INTRODUCTION: Although the diurnal fluctuation of motor dysfunction, reversible with small doses of dopamine, is a cornerstone for the phenotype of the autosomal dominant Segawa syndrome, the non-motor symptoms of this neurotransmitter deficiency have still received limited attention. OBJECTIVE: Thi...

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Autores principales: Alves Júnior, Ailton C., Daker, Maurício V., Machado, Alexei M.C., Luna, Alan S., Valladares Neto, Dirceu C., Valadares, Eugenia R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248209/
https://www.ncbi.nlm.nih.gov/pubmed/35782624
http://dx.doi.org/10.1016/j.ymgmr.2022.100870
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author Alves Júnior, Ailton C.
Daker, Maurício V.
Machado, Alexei M.C.
Luna, Alan S.
Valladares Neto, Dirceu C.
Valadares, Eugenia R.
author_facet Alves Júnior, Ailton C.
Daker, Maurício V.
Machado, Alexei M.C.
Luna, Alan S.
Valladares Neto, Dirceu C.
Valadares, Eugenia R.
author_sort Alves Júnior, Ailton C.
collection PubMed
description INTRODUCTION: Although the diurnal fluctuation of motor dysfunction, reversible with small doses of dopamine, is a cornerstone for the phenotype of the autosomal dominant Segawa syndrome, the non-motor symptoms of this neurotransmitter deficiency have still received limited attention. OBJECTIVE: This study aims to evaluate non-motor symptoms of this dopa-responsive dystonia through an intrafamilial comparative cross-sectional study. METHODS: Seventeen individuals with a c.IVS5 + 3insT (c.626 + 3insT) variation in the GTP cyclohydrolase-1 gene (GCH1, HGNC: 4193) and 34 intrafamilial controls were studied using the Beck Depression Inventory-II, the Wiener Matrizen Test 2, the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the MINI/MINI PLUS Questionnaires, the World Health Organization Quality of Life – BREF Instrument and a drug use assessment questionnaire. RESULTS: No significant difference was found between the groups in the prevalence of sleep disorders and in cognitive function. Nevertheless, generalized anxiety disorder (p = 0.050) and attention-deficit/hyperactivity disorder in childhood (p = 0.011) were observed only in individuals without the molecular variation. The group with the GCH1 variation presented a worse perception about how safe they feel in their daily lives (p = 0.034), less satisfaction with themselves (p = 0.049) and with their relationships (p = 0.029), and a higher prevalence of past major depressive episodes before use of L-Dopa (p = 0.046). CONCLUSION: Low dopamine could have been protective against generalized anxiety disorder and attention-deficit/hyperactivity disorder in childhood in Segawa group individuals. The prevalence of depression was higher in individuals with the molecular variant prior to the L-Dopa treatment. Considering it, the penetrance estimates for the variant carriers increased from 58.8% to up to 88% in this large studied family. Additionally, neuropsychiatric tests of all individuals with a molecular diagnosis in an affected family are a valuable instrument for its clinical management.
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spelling pubmed-92482092022-07-02 Neuropsychiatric and sleep study in autosomal dominant dopa-responsive dystonia Alves Júnior, Ailton C. Daker, Maurício V. Machado, Alexei M.C. Luna, Alan S. Valladares Neto, Dirceu C. Valadares, Eugenia R. Mol Genet Metab Rep Research Paper INTRODUCTION: Although the diurnal fluctuation of motor dysfunction, reversible with small doses of dopamine, is a cornerstone for the phenotype of the autosomal dominant Segawa syndrome, the non-motor symptoms of this neurotransmitter deficiency have still received limited attention. OBJECTIVE: This study aims to evaluate non-motor symptoms of this dopa-responsive dystonia through an intrafamilial comparative cross-sectional study. METHODS: Seventeen individuals with a c.IVS5 + 3insT (c.626 + 3insT) variation in the GTP cyclohydrolase-1 gene (GCH1, HGNC: 4193) and 34 intrafamilial controls were studied using the Beck Depression Inventory-II, the Wiener Matrizen Test 2, the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the MINI/MINI PLUS Questionnaires, the World Health Organization Quality of Life – BREF Instrument and a drug use assessment questionnaire. RESULTS: No significant difference was found between the groups in the prevalence of sleep disorders and in cognitive function. Nevertheless, generalized anxiety disorder (p = 0.050) and attention-deficit/hyperactivity disorder in childhood (p = 0.011) were observed only in individuals without the molecular variation. The group with the GCH1 variation presented a worse perception about how safe they feel in their daily lives (p = 0.034), less satisfaction with themselves (p = 0.049) and with their relationships (p = 0.029), and a higher prevalence of past major depressive episodes before use of L-Dopa (p = 0.046). CONCLUSION: Low dopamine could have been protective against generalized anxiety disorder and attention-deficit/hyperactivity disorder in childhood in Segawa group individuals. The prevalence of depression was higher in individuals with the molecular variant prior to the L-Dopa treatment. Considering it, the penetrance estimates for the variant carriers increased from 58.8% to up to 88% in this large studied family. Additionally, neuropsychiatric tests of all individuals with a molecular diagnosis in an affected family are a valuable instrument for its clinical management. Elsevier 2022-04-18 /pmc/articles/PMC9248209/ /pubmed/35782624 http://dx.doi.org/10.1016/j.ymgmr.2022.100870 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Paper
Alves Júnior, Ailton C.
Daker, Maurício V.
Machado, Alexei M.C.
Luna, Alan S.
Valladares Neto, Dirceu C.
Valadares, Eugenia R.
Neuropsychiatric and sleep study in autosomal dominant dopa-responsive dystonia
title Neuropsychiatric and sleep study in autosomal dominant dopa-responsive dystonia
title_full Neuropsychiatric and sleep study in autosomal dominant dopa-responsive dystonia
title_fullStr Neuropsychiatric and sleep study in autosomal dominant dopa-responsive dystonia
title_full_unstemmed Neuropsychiatric and sleep study in autosomal dominant dopa-responsive dystonia
title_short Neuropsychiatric and sleep study in autosomal dominant dopa-responsive dystonia
title_sort neuropsychiatric and sleep study in autosomal dominant dopa-responsive dystonia
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248209/
https://www.ncbi.nlm.nih.gov/pubmed/35782624
http://dx.doi.org/10.1016/j.ymgmr.2022.100870
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