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Association of norepinephrine transporter methylation with in vivo NET expression and hyperactivity–impulsivity symptoms in ADHD measured with PET

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a robust genetic influence. The norepinephrine transporter (NET) is of particular interest as it is one of the main targets in treatment of the disorder. As ADHD is a complex and polygenetic condition, the p...

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Autores principales: Sigurdardottir, H. L., Kranz, G. S., Rami-Mark, C., James, G. M., Vanicek, T., Gryglewski, G., Berroterán-Infante, N., Kautzky, A., Hienert, M., Traub-Weidinger, T., Mitterhauser, M., Wadsak, W., Hartmann, A. M., Hacker, M., Rujescu, D., Kasper, S., Lanzenberger, R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910214/
https://www.ncbi.nlm.nih.gov/pubmed/31383926
http://dx.doi.org/10.1038/s41380-019-0461-x
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author Sigurdardottir, H. L.
Kranz, G. S.
Rami-Mark, C.
James, G. M.
Vanicek, T.
Gryglewski, G.
Berroterán-Infante, N.
Kautzky, A.
Hienert, M.
Traub-Weidinger, T.
Mitterhauser, M.
Wadsak, W.
Hartmann, A. M.
Hacker, M.
Rujescu, D.
Kasper, S.
Lanzenberger, R.
author_facet Sigurdardottir, H. L.
Kranz, G. S.
Rami-Mark, C.
James, G. M.
Vanicek, T.
Gryglewski, G.
Berroterán-Infante, N.
Kautzky, A.
Hienert, M.
Traub-Weidinger, T.
Mitterhauser, M.
Wadsak, W.
Hartmann, A. M.
Hacker, M.
Rujescu, D.
Kasper, S.
Lanzenberger, R.
author_sort Sigurdardottir, H. L.
collection PubMed
description Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a robust genetic influence. The norepinephrine transporter (NET) is of particular interest as it is one of the main targets in treatment of the disorder. As ADHD is a complex and polygenetic condition, the possible regulation by epigenetic processes has received increased attention. We sought to determine possible differences in NET promoter DNA methylation between patients with ADHD and healthy controls. DNA methylation levels in the promoter region of the NET were determined in 23 adult patients with ADHD and 23 healthy controls. A subgroup of 18 patients with ADHD and 18 healthy controls underwent positron emission tomography (PET) with the radioligand (S,S)-[(18)F]FMeNER-D(2) to quantify the NET in several brain areas in vivo. Analyses revealed significant differences in NET methylation levels at several cytosine–phosphate–guanine (CpG) sites between groups. A defined segment of the NET promoter (“region 1”) was hypermethylated in patients in comparison with controls. In ADHD patients, a negative correlation between methylation of a CpG site in this region and NET distribution in the thalamus, locus coeruleus, and the raphe nuclei was detected. Furthermore, methylation of several sites in region 1 was negatively associated with the severity of hyperactivity–impulsivity symptoms. Our results point to an epigenetic dysregulation in ADHD, possibly due to a compensatory mechanisms or additional factors involved in transcriptional processing.
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spelling pubmed-79102142021-03-15 Association of norepinephrine transporter methylation with in vivo NET expression and hyperactivity–impulsivity symptoms in ADHD measured with PET Sigurdardottir, H. L. Kranz, G. S. Rami-Mark, C. James, G. M. Vanicek, T. Gryglewski, G. Berroterán-Infante, N. Kautzky, A. Hienert, M. Traub-Weidinger, T. Mitterhauser, M. Wadsak, W. Hartmann, A. M. Hacker, M. Rujescu, D. Kasper, S. Lanzenberger, R. Mol Psychiatry Article Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a robust genetic influence. The norepinephrine transporter (NET) is of particular interest as it is one of the main targets in treatment of the disorder. As ADHD is a complex and polygenetic condition, the possible regulation by epigenetic processes has received increased attention. We sought to determine possible differences in NET promoter DNA methylation between patients with ADHD and healthy controls. DNA methylation levels in the promoter region of the NET were determined in 23 adult patients with ADHD and 23 healthy controls. A subgroup of 18 patients with ADHD and 18 healthy controls underwent positron emission tomography (PET) with the radioligand (S,S)-[(18)F]FMeNER-D(2) to quantify the NET in several brain areas in vivo. Analyses revealed significant differences in NET methylation levels at several cytosine–phosphate–guanine (CpG) sites between groups. A defined segment of the NET promoter (“region 1”) was hypermethylated in patients in comparison with controls. In ADHD patients, a negative correlation between methylation of a CpG site in this region and NET distribution in the thalamus, locus coeruleus, and the raphe nuclei was detected. Furthermore, methylation of several sites in region 1 was negatively associated with the severity of hyperactivity–impulsivity symptoms. Our results point to an epigenetic dysregulation in ADHD, possibly due to a compensatory mechanisms or additional factors involved in transcriptional processing. Nature Publishing Group UK 2019-08-05 2021 /pmc/articles/PMC7910214/ /pubmed/31383926 http://dx.doi.org/10.1038/s41380-019-0461-x Text en © The Author(s) 2019 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Sigurdardottir, H. L.
Kranz, G. S.
Rami-Mark, C.
James, G. M.
Vanicek, T.
Gryglewski, G.
Berroterán-Infante, N.
Kautzky, A.
Hienert, M.
Traub-Weidinger, T.
Mitterhauser, M.
Wadsak, W.
Hartmann, A. M.
Hacker, M.
Rujescu, D.
Kasper, S.
Lanzenberger, R.
Association of norepinephrine transporter methylation with in vivo NET expression and hyperactivity–impulsivity symptoms in ADHD measured with PET
title Association of norepinephrine transporter methylation with in vivo NET expression and hyperactivity–impulsivity symptoms in ADHD measured with PET
title_full Association of norepinephrine transporter methylation with in vivo NET expression and hyperactivity–impulsivity symptoms in ADHD measured with PET
title_fullStr Association of norepinephrine transporter methylation with in vivo NET expression and hyperactivity–impulsivity symptoms in ADHD measured with PET
title_full_unstemmed Association of norepinephrine transporter methylation with in vivo NET expression and hyperactivity–impulsivity symptoms in ADHD measured with PET
title_short Association of norepinephrine transporter methylation with in vivo NET expression and hyperactivity–impulsivity symptoms in ADHD measured with PET
title_sort association of norepinephrine transporter methylation with in vivo net expression and hyperactivity–impulsivity symptoms in adhd measured with pet
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910214/
https://www.ncbi.nlm.nih.gov/pubmed/31383926
http://dx.doi.org/10.1038/s41380-019-0461-x
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