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Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

Prefrontal dopamine levels are relatively increased in adolescence compared to adulthood. Genetic variation of COMT (COMT Val158Met) results in lower enzymatic activity and higher dopamine availability in Met carriers. Given the dramatic changes of synaptic dopamine during adolescence, it has been s...

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Autores principales: Meyer, Bernhard M., Huemer, Julia, Rabl, Ulrich, Boubela, Roland N., Kalcher, Klaudius, Berger, Andreas, Banaschewski, Tobias, Barker, Gareth, Bokde, Arun, Büchel, Christian, Conrod, Patricia, Desrivières, Sylvane, Flor, Herta, Frouin, Vincent, Gallinat, Jurgen, Garavan, Hugh, Heinz, Andreas, Ittermann, Bernd, Jia, Tianye, Lathrop, Mark, Martinot, Jean-Luc, Nees, Frauke, Rietschel, Marcella, Smolka, Michael N., Bartova, Lucie, Popovic, Ana, Scharinger, Christian, Sitte, Harald H., Steiner, Hans, Friedrich, Max H., Kasper, Siegfried, Perkmann, Thomas, Praschak-Rieder, Nicole, Haslacher, Helmuth, Esterbauer, Harald, Moser, Ewald, Schumann, Gunter, Pezawas, Lukas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667398/
https://www.ncbi.nlm.nih.gov/pubmed/25319752
http://dx.doi.org/10.1007/s00429-014-0895-5
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author Meyer, Bernhard M.
Huemer, Julia
Rabl, Ulrich
Boubela, Roland N.
Kalcher, Klaudius
Berger, Andreas
Banaschewski, Tobias
Barker, Gareth
Bokde, Arun
Büchel, Christian
Conrod, Patricia
Desrivières, Sylvane
Flor, Herta
Frouin, Vincent
Gallinat, Jurgen
Garavan, Hugh
Heinz, Andreas
Ittermann, Bernd
Jia, Tianye
Lathrop, Mark
Martinot, Jean-Luc
Nees, Frauke
Rietschel, Marcella
Smolka, Michael N.
Bartova, Lucie
Popovic, Ana
Scharinger, Christian
Sitte, Harald H.
Steiner, Hans
Friedrich, Max H.
Kasper, Siegfried
Perkmann, Thomas
Praschak-Rieder, Nicole
Haslacher, Helmuth
Esterbauer, Harald
Moser, Ewald
Schumann, Gunter
Pezawas, Lukas
author_facet Meyer, Bernhard M.
Huemer, Julia
Rabl, Ulrich
Boubela, Roland N.
Kalcher, Klaudius
Berger, Andreas
Banaschewski, Tobias
Barker, Gareth
Bokde, Arun
Büchel, Christian
Conrod, Patricia
Desrivières, Sylvane
Flor, Herta
Frouin, Vincent
Gallinat, Jurgen
Garavan, Hugh
Heinz, Andreas
Ittermann, Bernd
Jia, Tianye
Lathrop, Mark
Martinot, Jean-Luc
Nees, Frauke
Rietschel, Marcella
Smolka, Michael N.
Bartova, Lucie
Popovic, Ana
Scharinger, Christian
Sitte, Harald H.
Steiner, Hans
Friedrich, Max H.
Kasper, Siegfried
Perkmann, Thomas
Praschak-Rieder, Nicole
Haslacher, Helmuth
Esterbauer, Harald
Moser, Ewald
Schumann, Gunter
Pezawas, Lukas
author_sort Meyer, Bernhard M.
collection PubMed
description Prefrontal dopamine levels are relatively increased in adolescence compared to adulthood. Genetic variation of COMT (COMT Val158Met) results in lower enzymatic activity and higher dopamine availability in Met carriers. Given the dramatic changes of synaptic dopamine during adolescence, it has been suggested that effects of COMT Val158Met genotypes might have oppositional effects in adolescents and adults. The present study aims to identify such oppositional COMT Val158Met effects in adolescents and adults in prefrontal brain networks at rest. Resting state functional connectivity data were collected from cross-sectional and multicenter study sites involving 106 healthy young adults (mean age 24 ± 2.6 years), gender matched to 106 randomly chosen 14-year-olds. We selected the anterior medial prefrontal cortex (amPFC) as seed due to its important role as nexus of the executive control and default mode network. We observed a significant age-dependent reversal of COMT Val158Met effects on resting state functional connectivity between amPFC and ventrolateral as well as dorsolateral prefrontal cortex, and parahippocampal gyrus. Val homozygous adults exhibited increased and adolescents decreased connectivity compared to Met homozygotes for all reported regions. Network analyses underscored the importance of the parahippocampal gyrus as mediator of observed effects. Results of this study demonstrate that adolescent and adult resting state networks are dose-dependently and diametrically affected by COMT genotypes following a hypothetical model of dopamine function that follows an inverted U-shaped curve. This study might provide cues for the understanding of disease onset or dopaminergic treatment mechanisms in major neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00429-014-0895-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-46673982016-01-25 Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults Meyer, Bernhard M. Huemer, Julia Rabl, Ulrich Boubela, Roland N. Kalcher, Klaudius Berger, Andreas Banaschewski, Tobias Barker, Gareth Bokde, Arun Büchel, Christian Conrod, Patricia Desrivières, Sylvane Flor, Herta Frouin, Vincent Gallinat, Jurgen Garavan, Hugh Heinz, Andreas Ittermann, Bernd Jia, Tianye Lathrop, Mark Martinot, Jean-Luc Nees, Frauke Rietschel, Marcella Smolka, Michael N. Bartova, Lucie Popovic, Ana Scharinger, Christian Sitte, Harald H. Steiner, Hans Friedrich, Max H. Kasper, Siegfried Perkmann, Thomas Praschak-Rieder, Nicole Haslacher, Helmuth Esterbauer, Harald Moser, Ewald Schumann, Gunter Pezawas, Lukas Brain Struct Funct Original Article Prefrontal dopamine levels are relatively increased in adolescence compared to adulthood. Genetic variation of COMT (COMT Val158Met) results in lower enzymatic activity and higher dopamine availability in Met carriers. Given the dramatic changes of synaptic dopamine during adolescence, it has been suggested that effects of COMT Val158Met genotypes might have oppositional effects in adolescents and adults. The present study aims to identify such oppositional COMT Val158Met effects in adolescents and adults in prefrontal brain networks at rest. Resting state functional connectivity data were collected from cross-sectional and multicenter study sites involving 106 healthy young adults (mean age 24 ± 2.6 years), gender matched to 106 randomly chosen 14-year-olds. We selected the anterior medial prefrontal cortex (amPFC) as seed due to its important role as nexus of the executive control and default mode network. We observed a significant age-dependent reversal of COMT Val158Met effects on resting state functional connectivity between amPFC and ventrolateral as well as dorsolateral prefrontal cortex, and parahippocampal gyrus. Val homozygous adults exhibited increased and adolescents decreased connectivity compared to Met homozygotes for all reported regions. Network analyses underscored the importance of the parahippocampal gyrus as mediator of observed effects. Results of this study demonstrate that adolescent and adult resting state networks are dose-dependently and diametrically affected by COMT genotypes following a hypothetical model of dopamine function that follows an inverted U-shaped curve. This study might provide cues for the understanding of disease onset or dopaminergic treatment mechanisms in major neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00429-014-0895-5) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2014-10-16 2016 /pmc/articles/PMC4667398/ /pubmed/25319752 http://dx.doi.org/10.1007/s00429-014-0895-5 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Article
Meyer, Bernhard M.
Huemer, Julia
Rabl, Ulrich
Boubela, Roland N.
Kalcher, Klaudius
Berger, Andreas
Banaschewski, Tobias
Barker, Gareth
Bokde, Arun
Büchel, Christian
Conrod, Patricia
Desrivières, Sylvane
Flor, Herta
Frouin, Vincent
Gallinat, Jurgen
Garavan, Hugh
Heinz, Andreas
Ittermann, Bernd
Jia, Tianye
Lathrop, Mark
Martinot, Jean-Luc
Nees, Frauke
Rietschel, Marcella
Smolka, Michael N.
Bartova, Lucie
Popovic, Ana
Scharinger, Christian
Sitte, Harald H.
Steiner, Hans
Friedrich, Max H.
Kasper, Siegfried
Perkmann, Thomas
Praschak-Rieder, Nicole
Haslacher, Helmuth
Esterbauer, Harald
Moser, Ewald
Schumann, Gunter
Pezawas, Lukas
Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults
title Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults
title_full Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults
title_fullStr Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults
title_full_unstemmed Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults
title_short Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults
title_sort oppositional comt val158met effects on resting state functional connectivity in adolescents and adults
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667398/
https://www.ncbi.nlm.nih.gov/pubmed/25319752
http://dx.doi.org/10.1007/s00429-014-0895-5
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