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Auteur S. HUSON |
Documents disponibles écrits par cet auteur (2)
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Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA) / S. STIVAROS in Molecular Autism, 9 (2018)
[article]
Titre : Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA) Type de document : Texte imprimé et/ou numérique Auteurs : S. STIVAROS, Auteur ; S. GARG, Auteur ; M. TZIRAKI, Auteur ; Y. CAI, Auteur ; O. THOMAS, Auteur ; J. MELLOR, Auteur ; A. A. MORRIS, Auteur ; C. JIM, Auteur ; K. SZUMANSKA-RYT, Auteur ; L. M. PARKES, Auteur ; H. A. HAROON, Auteur ; D. MONTALDI, Auteur ; N. WEBB, Auteur ; J. KEANE, Auteur ; Francisco Xavier CASTELLANOS, Auteur ; A. J. SILVA, Auteur ; S. HUSON, Auteur ; S. WILLIAMS, Auteur ; D. GARETH EVANS, Auteur ; R. EMSLEY, Auteur ; J. GREEN, Auteur Article en page(s) : 12p. Langues : Anglais (eng) Mots-clés : Autism Neurofibromatosis type 1 Neuroimaging Randomised controlled trial Simvastatin Statin Index. décimale : PER Périodiques Résumé : Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods: A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results: Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA (t(12) = - 2.12, p = .055), GABA/Glx ratio (t(12) = - 2.78, p = .016), and reduced grey nuclei Glx (ANCOVA p < 0.05, Mann-Whitney p < 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney p < 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney p < 0.01). Machine-learning classification of imaging outcomes achieved 79% (p < .05) accuracy differentiating groups at endpoint against chance level (64%, p = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met 'clinical responder' criteria for behavioural outcome. Conclusions: We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network. Trial registration: EU Clinical Trial Register (EudraCT) 2012-005742-38 (www.clinicaltrialsregister.eu). En ligne : http://dx.doi.org/10.1186/s13229-018-0190-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354
in Molecular Autism > 9 (2018) . - 12p.[article] Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA) [Texte imprimé et/ou numérique] / S. STIVAROS, Auteur ; S. GARG, Auteur ; M. TZIRAKI, Auteur ; Y. CAI, Auteur ; O. THOMAS, Auteur ; J. MELLOR, Auteur ; A. A. MORRIS, Auteur ; C. JIM, Auteur ; K. SZUMANSKA-RYT, Auteur ; L. M. PARKES, Auteur ; H. A. HAROON, Auteur ; D. MONTALDI, Auteur ; N. WEBB, Auteur ; J. KEANE, Auteur ; Francisco Xavier CASTELLANOS, Auteur ; A. J. SILVA, Auteur ; S. HUSON, Auteur ; S. WILLIAMS, Auteur ; D. GARETH EVANS, Auteur ; R. EMSLEY, Auteur ; J. GREEN, Auteur . - 12p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 12p.
Mots-clés : Autism Neurofibromatosis type 1 Neuroimaging Randomised controlled trial Simvastatin Statin Index. décimale : PER Périodiques Résumé : Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods: A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results: Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA (t(12) = - 2.12, p = .055), GABA/Glx ratio (t(12) = - 2.78, p = .016), and reduced grey nuclei Glx (ANCOVA p < 0.05, Mann-Whitney p < 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney p < 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney p < 0.01). Machine-learning classification of imaging outcomes achieved 79% (p < .05) accuracy differentiating groups at endpoint against chance level (64%, p = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met 'clinical responder' criteria for behavioural outcome. Conclusions: We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network. Trial registration: EU Clinical Trial Register (EudraCT) 2012-005742-38 (www.clinicaltrialsregister.eu). En ligne : http://dx.doi.org/10.1186/s13229-018-0190-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354 Sex bias in autism spectrum disorder in neurofibromatosis type 1 / S. GARG in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)
[article]
Titre : Sex bias in autism spectrum disorder in neurofibromatosis type 1 Type de document : Texte imprimé et/ou numérique Auteurs : S. GARG, Auteur ; Hein HEUVELMAN, Auteur ; S. HUSON, Auteur ; H. TOBIN, Auteur ; J. GREEN, Auteur Article en page(s) : p.26 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Neurofibromatosis type 1 Sex bias Syndromic autism Index. décimale : PER Périodiques Résumé : BACKGROUND: Despite extensive literature, little is known about the mechanisms underlying sex bias in autism spectrum disorder (ASD). This study investigates the sex differences in ASD associated with neurofibromatosis type 1, a single-gene model of syndromic autism. METHODS: We analysed data from n = 194 children aged 4-16 years with neurofibromatosis type 1. Sex differences were evaluated across the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), verbal IQ, Social Responsiveness Scale (SRS) and Conners questionnaires. RESULTS: There was 2.68:1 male:female ratio in children meeting ASD criteria on the deep phenotyping measures. On symptom profile, males with neurofibromatosis type 1 (NF1) + ASD were more impaired on reciprocal social interaction and communication domains of the ADI-R but we found no differences on the restricted, repetitive behaviours (RRBs) domain of the ADI-R and no differences on the social on the ADOS. NF1 ASD males and females were comparable on verbal IQ, and the inattention/hyperactivity domains of the Conners questionnaire. CONCLUSIONS: There is a significant male bias in the prevalence of ASD in NF1. The phenotypic profile of NF1 + ASD cases includes greater social communication impairment in males. We discuss the implications of our findings and the rationale for using NF1 as a model for investigating sex bias in idiopathic ASD. En ligne : http://dx.doi.org/10.1186/s11689-016-9159-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349
in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.26[article] Sex bias in autism spectrum disorder in neurofibromatosis type 1 [Texte imprimé et/ou numérique] / S. GARG, Auteur ; Hein HEUVELMAN, Auteur ; S. HUSON, Auteur ; H. TOBIN, Auteur ; J. GREEN, Auteur . - p.26.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.26
Mots-clés : Autism spectrum disorder Neurofibromatosis type 1 Sex bias Syndromic autism Index. décimale : PER Périodiques Résumé : BACKGROUND: Despite extensive literature, little is known about the mechanisms underlying sex bias in autism spectrum disorder (ASD). This study investigates the sex differences in ASD associated with neurofibromatosis type 1, a single-gene model of syndromic autism. METHODS: We analysed data from n = 194 children aged 4-16 years with neurofibromatosis type 1. Sex differences were evaluated across the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), verbal IQ, Social Responsiveness Scale (SRS) and Conners questionnaires. RESULTS: There was 2.68:1 male:female ratio in children meeting ASD criteria on the deep phenotyping measures. On symptom profile, males with neurofibromatosis type 1 (NF1) + ASD were more impaired on reciprocal social interaction and communication domains of the ADI-R but we found no differences on the restricted, repetitive behaviours (RRBs) domain of the ADI-R and no differences on the social on the ADOS. NF1 ASD males and females were comparable on verbal IQ, and the inattention/hyperactivity domains of the Conners questionnaire. CONCLUSIONS: There is a significant male bias in the prevalence of ASD in NF1. The phenotypic profile of NF1 + ASD cases includes greater social communication impairment in males. We discuss the implications of our findings and the rationale for using NF1 as a model for investigating sex bias in idiopathic ASD. En ligne : http://dx.doi.org/10.1186/s11689-016-9159-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349