A common genetic variant in fatty acid amide hydrolase is linked to alterations in fear extinction neural circuitry in a racially diverse, nonclinical sample of adults.
amygdala
aversive
endocannabinoids
genetic polymorphism
magnetic resonance imaging
prefrontal cortex
Journal
Journal of neuroscience research
ISSN: 1097-4547
Titre abrégé: J Neurosci Res
Pays: United States
ID NLM: 7600111
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
14
04
2021
received:
01
02
2021
accepted:
06
05
2021
pubmed:
30
5
2021
medline:
1
4
2022
entrez:
29
5
2021
Statut:
ppublish
Résumé
Poor fear extinction learning and recall are linked to the development of fear-based disorders, like posttraumatic stress disorder, and are associated with aberrant activation of fear-related neural circuitry. This includes greater amygdala activation during extinction learning and lesser hippocampal and ventromedial prefrontal cortex (vmPFC) activation during recall. Emerging data indicate that genetic variation in fatty acid amide hydrolase (FAAH C385A; rs324420) is associated with increased peripheral endocannabinoid (eCB) levels and lesser threat-related amygdala reactivity. Preclinical studies link increased eCB signaling to better extinction learning and recall, thus FAAH C385A may protect against the development of trauma-related psychopathology by facilitating extinction learning. However, how this FAAH variant affects fear extinction neural circuitry remains unknown. In the present study, we used a novel, immersive-reality fear extinction paradigm paired with functional neuroimaging to assess FAAH C385A effects on fear-related neural circuitry and conditioned fear responding (US expectancy ratings, subjective units of distress, and skin conductance responding) in healthy adults from an urban area (Detroit, MI; N = 59; C/C = 35, A-carrier = 24). We found lesser amygdala activation in A-allele carriers, compared to C/C homozygotes, during early extinction recall. Likewise, we found lesser dorsal anterior cingulate cortex and greater hippocampus activation in early extinction learning in A-carriers compared to C/C homozygotes. We found no effects of FAAH C385A on vmPFC activation or behavioral fear indices. These data support and extend previous findings that FAAH genetic variation, associated with increased eCB signaling and subsequent enhanced fear extinction, may predict individual differences in successful fear learning.
Identifiants
pubmed: 34051704
doi: 10.1002/jnr.24860
pmc: PMC8628026
mid: NIHMS1721956
doi:
Substances chimiques
Amidohydrolases
EC 3.5.-
fatty-acid amide hydrolase
EC 3.5.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
744-761Subventions
Organisme : NIDDK NIH HHS
ID : K23 DK118199
Pays : United States
Organisme : NIDDK NIH HHS
ID : L30 DK110823
Pays : United States
Organisme : NIMH NIH HHS
ID : K01 MH119241
Pays : United States
Organisme : NIMH NIH HHS
ID : R61 MH111935
Pays : United States
Organisme : NIMH NIH HHS
ID : F31 MH124279
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
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