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Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis

While psychotic experiences (PEs) are assumed to represent psychosis liability, general population studies have not been able to establish significant associations between polygenic risk scores (PRS) and PEs. Previous work suggests that PEs may only represent significant risk when accompanied by soc...

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Autores principales: Velthorst, Eva, Froudist-Walsh, Sean, Stahl, Eli, Ruderfer, Douglas, Ivanov, Ilyan, Buxbaum, Joseph, Banaschewski, Tobias, Bokde, Arun L. W., Dipl-Psych, Uli Bromberg, Büchel, Christian, Quinlan, Erin Burke, Desrivières, Sylvane, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Marie-Laure Paillère, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomáš, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Schumann, Gunter, Reichenberg, Abraham
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158250/
https://www.ncbi.nlm.nih.gov/pubmed/30258131
http://dx.doi.org/10.1038/s41398-018-0229-0
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author Velthorst, Eva
Froudist-Walsh, Sean
Stahl, Eli
Ruderfer, Douglas
Ivanov, Ilyan
Buxbaum, Joseph
Banaschewski, Tobias
Bokde, Arun L. W.
Dipl-Psych, Uli Bromberg
Büchel, Christian
Quinlan, Erin Burke
Desrivières, Sylvane
Flor, Herta
Frouin, Vincent
Garavan, Hugh
Gowland, Penny
Heinz, Andreas
Ittermann, Bernd
Martinot, Marie-Laure Paillère
Artiges, Eric
Nees, Frauke
Orfanos, Dimitri Papadopoulos
Paus, Tomáš
Poustka, Luise
Hohmann, Sarah
Fröhner, Juliane H.
Smolka, Michael N.
Walter, Henrik
Whelan, Robert
Schumann, Gunter
Reichenberg, Abraham
author_facet Velthorst, Eva
Froudist-Walsh, Sean
Stahl, Eli
Ruderfer, Douglas
Ivanov, Ilyan
Buxbaum, Joseph
Banaschewski, Tobias
Bokde, Arun L. W.
Dipl-Psych, Uli Bromberg
Büchel, Christian
Quinlan, Erin Burke
Desrivières, Sylvane
Flor, Herta
Frouin, Vincent
Garavan, Hugh
Gowland, Penny
Heinz, Andreas
Ittermann, Bernd
Martinot, Marie-Laure Paillère
Artiges, Eric
Nees, Frauke
Orfanos, Dimitri Papadopoulos
Paus, Tomáš
Poustka, Luise
Hohmann, Sarah
Fröhner, Juliane H.
Smolka, Michael N.
Walter, Henrik
Whelan, Robert
Schumann, Gunter
Reichenberg, Abraham
author_sort Velthorst, Eva
collection PubMed
description While psychotic experiences (PEs) are assumed to represent psychosis liability, general population studies have not been able to establish significant associations between polygenic risk scores (PRS) and PEs. Previous work suggests that PEs may only represent significant risk when accompanied by social impairment. Leveraging data from the large longitudinal IMAGEN cohort, including 2096 14-year old adolescents that were followed-up to age 18, we tested whether the association between polygenic risk and PEs is mediated by (increasing) impairments in social functioning and social cognitive processes. Using structural equation modeling (SEM) for the subset of participants (n = 643) with complete baseline and follow-up data, we examined pathways to PEs. We found that high polygenic risk for schizophrenia (p = 0.014), reduced brain activity to emotional stimuli (p = 0.009) and social impairments in late adolescence (p < 0.001; controlling for functioning in early adolescence) each independently contributed to the severity of PEs at age 18. The pathway between polygenic risk for autism spectrum disorder and PEs was mediated by social impairments in late adolescence (indirect pathway; p = 0.025). These findings point to multiple direct and indirect pathways to PEs, suggesting that different processes are in play, depending on genetic loading, and environment. Our results suggest that treatments targeting prevention of social impairment may be particularly promising for individuals at genetic risk for autism in order to minimize risk for psychosis.
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spelling pubmed-61582502018-09-28 Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis Velthorst, Eva Froudist-Walsh, Sean Stahl, Eli Ruderfer, Douglas Ivanov, Ilyan Buxbaum, Joseph Banaschewski, Tobias Bokde, Arun L. W. Dipl-Psych, Uli Bromberg Büchel, Christian Quinlan, Erin Burke Desrivières, Sylvane Flor, Herta Frouin, Vincent Garavan, Hugh Gowland, Penny Heinz, Andreas Ittermann, Bernd Martinot, Marie-Laure Paillère Artiges, Eric Nees, Frauke Orfanos, Dimitri Papadopoulos Paus, Tomáš Poustka, Luise Hohmann, Sarah Fröhner, Juliane H. Smolka, Michael N. Walter, Henrik Whelan, Robert Schumann, Gunter Reichenberg, Abraham Transl Psychiatry Article While psychotic experiences (PEs) are assumed to represent psychosis liability, general population studies have not been able to establish significant associations between polygenic risk scores (PRS) and PEs. Previous work suggests that PEs may only represent significant risk when accompanied by social impairment. Leveraging data from the large longitudinal IMAGEN cohort, including 2096 14-year old adolescents that were followed-up to age 18, we tested whether the association between polygenic risk and PEs is mediated by (increasing) impairments in social functioning and social cognitive processes. Using structural equation modeling (SEM) for the subset of participants (n = 643) with complete baseline and follow-up data, we examined pathways to PEs. We found that high polygenic risk for schizophrenia (p = 0.014), reduced brain activity to emotional stimuli (p = 0.009) and social impairments in late adolescence (p < 0.001; controlling for functioning in early adolescence) each independently contributed to the severity of PEs at age 18. The pathway between polygenic risk for autism spectrum disorder and PEs was mediated by social impairments in late adolescence (indirect pathway; p = 0.025). These findings point to multiple direct and indirect pathways to PEs, suggesting that different processes are in play, depending on genetic loading, and environment. Our results suggest that treatments targeting prevention of social impairment may be particularly promising for individuals at genetic risk for autism in order to minimize risk for psychosis. Nature Publishing Group UK 2018-09-26 /pmc/articles/PMC6158250/ /pubmed/30258131 http://dx.doi.org/10.1038/s41398-018-0229-0 Text en © The Author(s) 2018 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
Velthorst, Eva
Froudist-Walsh, Sean
Stahl, Eli
Ruderfer, Douglas
Ivanov, Ilyan
Buxbaum, Joseph
Banaschewski, Tobias
Bokde, Arun L. W.
Dipl-Psych, Uli Bromberg
Büchel, Christian
Quinlan, Erin Burke
Desrivières, Sylvane
Flor, Herta
Frouin, Vincent
Garavan, Hugh
Gowland, Penny
Heinz, Andreas
Ittermann, Bernd
Martinot, Marie-Laure Paillère
Artiges, Eric
Nees, Frauke
Orfanos, Dimitri Papadopoulos
Paus, Tomáš
Poustka, Luise
Hohmann, Sarah
Fröhner, Juliane H.
Smolka, Michael N.
Walter, Henrik
Whelan, Robert
Schumann, Gunter
Reichenberg, Abraham
Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis
title Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis
title_full Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis
title_fullStr Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis
title_full_unstemmed Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis
title_short Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis
title_sort genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158250/
https://www.ncbi.nlm.nih.gov/pubmed/30258131
http://dx.doi.org/10.1038/s41398-018-0229-0
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