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FAAH polymorphism (rs324420) modulates extinction recall in healthy humans: an fMRI study

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Názov: FAAH polymorphism (rs324420) modulates extinction recall in healthy humans: an fMRI study
Autori: Jennifer Spohrs, Martin Ulrich, Georg Grön, Paul L. Plener, Birgit Abler
Zdroj: Eur Arch Psychiatry Clin Neurosci
Informácie o vydavateľovi: Springer Science and Business Media LLC, 2021.
Rok vydania: 2021
Predmety: Extinction recall, Adult, Male, Original Paper, Anandamide, Adult [MeSH], Humans [MeSH], FAAH rs324420, Animals [MeSH], Anxiety disorders, Polymorphism, Single Nucleotide/genetics [MeSH], Magnetic Resonance Imaging [MeSH], Male [MeSH], Endocannabinoids [MeSH], Endocannabinoid system, Extinction, Psychological/physiology [MeSH], Fear/physiology [MeSH], Fear, Magnetic Resonance Imaging, Polymorphism, Single Nucleotide, Extinction, Psychological, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, Endocannabinoids
Popis: Gold standard treatments for anxiety- and trauma-related disorders focus on exposure therapy promoting extinction learning and extinction retention. However, its efficacy is limited. Preclinical and particularly animal research has been able to demonstrate that homozygosity for the fatty acid amide hydrolase (FAAH) C385A allele, similar to FAAH inhibition, is associated with elevated concentrations of anandamide (AEA) and facilitates extinction learning and extinction recall. However, in humans, the underlying neurobiological processes are less well understood, and further knowledge might enhance the development of more effective therapies. In this functional magnetic resonance imaging (fMRI) study, a fear conditioning, fear extinction and extinction recall paradigm was conducted with 55 healthy male adults. They were genotyped for the FAAH single-nucleotide polymorphism (SNP) rs324420 to investigate differences related to extinction recall in neural activation and State–Trait Anxiety Inventory (STAI) ratings between AC heterozygotes and CC homozygotes (FAAH C385A SNP). Differential brain activation upon an unextinguished relative to an extinguished stimulus, was greater in AC heterozygotes as compared to CC homozygotes in core neural structures previously related to extinction recall, such as the medial superior frontal gyrus, the dorsal anterior cingulate and the anterior and middle insular cortex. Furthermore, AC heterozygotes displayed higher AEA levels and lower STAI-state ratings. Our data can be interpreted in line with previous suggestions of more successful extinction recall in A-allele carriers with elevated AEA levels. Data corroborate the hypothesis that the endocannabinoid system, particularly AEA, plays a modulatory role in the extinction of aversive memory.
Druh dokumentu: Article
Other literature type
Popis súboru: application/pdf
Jazyk: English
ISSN: 1433-8491
0940-1334
DOI: 10.1007/s00406-021-01367-4
DOI: 10.18725/oparu-51076
Prístupová URL adresa: https://link.springer.com/content/pdf/10.1007/s00406-021-01367-4.pdf
https://pubmed.ncbi.nlm.nih.gov/34893921
https://repository.publisso.de/resource/frl:6447220
Rights: CC BY
URL: http://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) .
Prístupové číslo: edsair.doi.dedup.....46af922f6b45e7e6c15ab667dcbd07f2
Databáza: OpenAIRE
Popis
Abstrakt:Gold standard treatments for anxiety- and trauma-related disorders focus on exposure therapy promoting extinction learning and extinction retention. However, its efficacy is limited. Preclinical and particularly animal research has been able to demonstrate that homozygosity for the fatty acid amide hydrolase (FAAH) C385A allele, similar to FAAH inhibition, is associated with elevated concentrations of anandamide (AEA) and facilitates extinction learning and extinction recall. However, in humans, the underlying neurobiological processes are less well understood, and further knowledge might enhance the development of more effective therapies. In this functional magnetic resonance imaging (fMRI) study, a fear conditioning, fear extinction and extinction recall paradigm was conducted with 55 healthy male adults. They were genotyped for the FAAH single-nucleotide polymorphism (SNP) rs324420 to investigate differences related to extinction recall in neural activation and State–Trait Anxiety Inventory (STAI) ratings between AC heterozygotes and CC homozygotes (FAAH C385A SNP). Differential brain activation upon an unextinguished relative to an extinguished stimulus, was greater in AC heterozygotes as compared to CC homozygotes in core neural structures previously related to extinction recall, such as the medial superior frontal gyrus, the dorsal anterior cingulate and the anterior and middle insular cortex. Furthermore, AC heterozygotes displayed higher AEA levels and lower STAI-state ratings. Our data can be interpreted in line with previous suggestions of more successful extinction recall in A-allele carriers with elevated AEA levels. Data corroborate the hypothesis that the endocannabinoid system, particularly AEA, plays a modulatory role in the extinction of aversive memory.
ISSN:14338491
09401334
DOI:10.1007/s00406-021-01367-4