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The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders
Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259991/ https://www.ncbi.nlm.nih.gov/pubmed/25386956 http://dx.doi.org/10.1038/tp.2014.120 |
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author | Pagan, C Delorme, R Callebert, J Goubran-Botros, H Amsellem, F Drouot, X Boudebesse, C Le Dudal, K Ngo-Nguyen, N Laouamri, H Gillberg, C Leboyer, M Bourgeron, T Launay, J-M |
author_facet | Pagan, C Delorme, R Callebert, J Goubran-Botros, H Amsellem, F Drouot, X Boudebesse, C Le Dudal, K Ngo-Nguyen, N Laouamri, H Gillberg, C Leboyer, M Bourgeron, T Launay, J-M |
author_sort | Pagan, C |
collection | PubMed |
description | Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35–46%) of patients), as well as the deficit in melatonin (51% (45–57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41–54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS–melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS–melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD. |
format | Online Article Text |
id | pubmed-4259991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-42599912014-12-12 The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders Pagan, C Delorme, R Callebert, J Goubran-Botros, H Amsellem, F Drouot, X Boudebesse, C Le Dudal, K Ngo-Nguyen, N Laouamri, H Gillberg, C Leboyer, M Bourgeron, T Launay, J-M Transl Psychiatry Original Article Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35–46%) of patients), as well as the deficit in melatonin (51% (45–57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41–54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS–melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS–melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD. Nature Publishing Group 2014-11 2014-11-11 /pmc/articles/PMC4259991/ /pubmed/25386956 http://dx.doi.org/10.1038/tp.2014.120 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Original Article Pagan, C Delorme, R Callebert, J Goubran-Botros, H Amsellem, F Drouot, X Boudebesse, C Le Dudal, K Ngo-Nguyen, N Laouamri, H Gillberg, C Leboyer, M Bourgeron, T Launay, J-M The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders |
title | The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders |
title_full | The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders |
title_fullStr | The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders |
title_full_unstemmed | The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders |
title_short | The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders |
title_sort | serotonin-n-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259991/ https://www.ncbi.nlm.nih.gov/pubmed/25386956 http://dx.doi.org/10.1038/tp.2014.120 |
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