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Contextual fear conditioning in virtual reality is affected by 5HTTLPR and NPSR1 polymorphisms: effects on fear-potentiated startle

The serotonin (5-HT) and neuropeptide S (NPS) systems are discussed as important genetic modulators of fear and sustained anxiety contributing to the etiology of anxiety disorders. Sustained anxiety is a crucial characteristic of most anxiety disorders which likely develops through contextual fear c...

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Autores principales: Glotzbach-Schoon, Evelyn, Andreatta, Marta, Reif, Andreas, Ewald, Heike, Tröger, Christian, Baumann, Christian, Deckert, Jürgen, Mühlberger, Andreas, Pauli, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632789/
https://www.ncbi.nlm.nih.gov/pubmed/23630477
http://dx.doi.org/10.3389/fnbeh.2013.00031
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author Glotzbach-Schoon, Evelyn
Andreatta, Marta
Reif, Andreas
Ewald, Heike
Tröger, Christian
Baumann, Christian
Deckert, Jürgen
Mühlberger, Andreas
Pauli, Paul
author_facet Glotzbach-Schoon, Evelyn
Andreatta, Marta
Reif, Andreas
Ewald, Heike
Tröger, Christian
Baumann, Christian
Deckert, Jürgen
Mühlberger, Andreas
Pauli, Paul
author_sort Glotzbach-Schoon, Evelyn
collection PubMed
description The serotonin (5-HT) and neuropeptide S (NPS) systems are discussed as important genetic modulators of fear and sustained anxiety contributing to the etiology of anxiety disorders. Sustained anxiety is a crucial characteristic of most anxiety disorders which likely develops through contextual fear conditioning. This study investigated if and how genetic alterations of the 5-HT and the NPS systems as well as their interaction modulate contextual fear conditioning; specifically, function polymorphic variants in the genes coding for the 5-HT transporter (5HTT) and the NPS receptor (NPSR1) were studied. A large group of healthy volunteers was therefore stratified for 5HTTLPR (S+ vs. LL carriers) and NPSR1 rs324981 (T+ vs. AA carriers) polymorphisms resulting in four genotype groups (S+/T+, S+/AA, LL/T+, LL/AA) of 20 participants each. All participants underwent contextual fear conditioning and extinction using a virtual reality (VR) paradigm. During acquisition, one virtual office room (anxiety context, CXT+) was paired with an unpredictable electric stimulus (unconditioned stimulus, US), whereas another virtual office room was not paired with any US (safety context, CXT−). During extinction no US was administered. Anxiety responses were quantified by fear-potentiated startle and ratings. Most importantly, we found a gene × gene interaction on fear-potentiated startle. Only carriers of both risk alleles (S+/T+) exhibited higher startle responses in CXT+ compared to CXT−. In contrast, anxiety ratings were only influenced by the NPSR1 polymorphism with AA carriers showing higher anxiety ratings in CXT+ as compared to CXT−. Our results speak in favor of a two level account of fear conditioning with diverging effects on implicit vs. explicit fear responses. Enhanced contextual fear conditioning as reflected in potentiated startle responses may be an endophenotype for anxiety disorders.
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spelling pubmed-36327892013-04-29 Contextual fear conditioning in virtual reality is affected by 5HTTLPR and NPSR1 polymorphisms: effects on fear-potentiated startle Glotzbach-Schoon, Evelyn Andreatta, Marta Reif, Andreas Ewald, Heike Tröger, Christian Baumann, Christian Deckert, Jürgen Mühlberger, Andreas Pauli, Paul Front Behav Neurosci Neuroscience The serotonin (5-HT) and neuropeptide S (NPS) systems are discussed as important genetic modulators of fear and sustained anxiety contributing to the etiology of anxiety disorders. Sustained anxiety is a crucial characteristic of most anxiety disorders which likely develops through contextual fear conditioning. This study investigated if and how genetic alterations of the 5-HT and the NPS systems as well as their interaction modulate contextual fear conditioning; specifically, function polymorphic variants in the genes coding for the 5-HT transporter (5HTT) and the NPS receptor (NPSR1) were studied. A large group of healthy volunteers was therefore stratified for 5HTTLPR (S+ vs. LL carriers) and NPSR1 rs324981 (T+ vs. AA carriers) polymorphisms resulting in four genotype groups (S+/T+, S+/AA, LL/T+, LL/AA) of 20 participants each. All participants underwent contextual fear conditioning and extinction using a virtual reality (VR) paradigm. During acquisition, one virtual office room (anxiety context, CXT+) was paired with an unpredictable electric stimulus (unconditioned stimulus, US), whereas another virtual office room was not paired with any US (safety context, CXT−). During extinction no US was administered. Anxiety responses were quantified by fear-potentiated startle and ratings. Most importantly, we found a gene × gene interaction on fear-potentiated startle. Only carriers of both risk alleles (S+/T+) exhibited higher startle responses in CXT+ compared to CXT−. In contrast, anxiety ratings were only influenced by the NPSR1 polymorphism with AA carriers showing higher anxiety ratings in CXT+ as compared to CXT−. Our results speak in favor of a two level account of fear conditioning with diverging effects on implicit vs. explicit fear responses. Enhanced contextual fear conditioning as reflected in potentiated startle responses may be an endophenotype for anxiety disorders. Frontiers Media S.A. 2013-04-23 /pmc/articles/PMC3632789/ /pubmed/23630477 http://dx.doi.org/10.3389/fnbeh.2013.00031 Text en Copyright © 2013 Glotzbach-Schoon, Andreatta, Reif, Ewald, Tröger, Baumann, Deckert, Mühlberger and Pauli. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Neuroscience
Glotzbach-Schoon, Evelyn
Andreatta, Marta
Reif, Andreas
Ewald, Heike
Tröger, Christian
Baumann, Christian
Deckert, Jürgen
Mühlberger, Andreas
Pauli, Paul
Contextual fear conditioning in virtual reality is affected by 5HTTLPR and NPSR1 polymorphisms: effects on fear-potentiated startle
title Contextual fear conditioning in virtual reality is affected by 5HTTLPR and NPSR1 polymorphisms: effects on fear-potentiated startle
title_full Contextual fear conditioning in virtual reality is affected by 5HTTLPR and NPSR1 polymorphisms: effects on fear-potentiated startle
title_fullStr Contextual fear conditioning in virtual reality is affected by 5HTTLPR and NPSR1 polymorphisms: effects on fear-potentiated startle
title_full_unstemmed Contextual fear conditioning in virtual reality is affected by 5HTTLPR and NPSR1 polymorphisms: effects on fear-potentiated startle
title_short Contextual fear conditioning in virtual reality is affected by 5HTTLPR and NPSR1 polymorphisms: effects on fear-potentiated startle
title_sort contextual fear conditioning in virtual reality is affected by 5httlpr and npsr1 polymorphisms: effects on fear-potentiated startle
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632789/
https://www.ncbi.nlm.nih.gov/pubmed/23630477
http://dx.doi.org/10.3389/fnbeh.2013.00031
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