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Crombie KM, Privratsky AA, Schomaker CM, et al. The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD. Neuroimage Clin. 2021;33:102922doi: 10.1016/j.nicl.2021.102922.
Crombie, K. M., Privratsky, A. A., Schomaker, C. M., Heilicher, M., Ross, M. C., Sartin-Tarm, A., Sellnow, K., Binder, E. B., Andrew James, G., & Cisler, J. M. (2021). The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD. NeuroImage. Clinical, 33102922. https://doi.org/10.1016/j.nicl.2021.102922
Crombie, Kevin M, et al. "The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD." NeuroImage. Clinical vol. 33 (2021): 102922. doi: https://doi.org/10.1016/j.nicl.2021.102922
Crombie KM, Privratsky AA, Schomaker CM, Heilicher M, Ross MC, Sartin-Tarm A, Sellnow K, Binder EB, Andrew James G, Cisler JM. The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD. Neuroimage Clin. 2021 Dec 20;33:102922. doi: 10.1016/j.nicl.2021.102922. Epub 2021 Dec 20. PMID: 34952353; PMCID: PMC8715233.
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Neuroimage Clin. 2021 Dec 20;33:102922. doi: 10.1016/j.nicl.2021.102922. Epub 2021 Dec 20.

The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD.

NeuroImage. Clinical

Kevin M Crombie, Anthony A Privratsky, Chloe M Schomaker, Mickela Heilicher, Marisa C Ross, Anneliis Sartin-Tarm, Kyrie Sellnow, Elisabeth B Binder, G Andrew James, Josh M Cisler

Affiliations

  1. The University of Texas at Austin, Department of Psychiatry and Behavioral Sciences, Health Discovery Building, 1601 Trinity St., Building B, Austin, TX 78712, USA. Electronic address: [email protected].
  2. University of Arkansas for Medical Sciences, Brain Imaging Research Center, 4301 W. Markham Street #554, Little Rock, AR 72205, USA.
  3. The University of Texas at Austin, Department of Psychiatry and Behavioral Sciences, Health Discovery Building, 1601 Trinity St., Building B, Austin, TX 78712, USA.
  4. University of Wisconsin - Madison, Department of Psychiatry, 6001 Research Park Boulevard, Madison, WI 53719-1176608-262-6375, USA.
  5. Max Planck Institute of Psychiatry, Department of Translational Psychiatry, Kraepelinstr. 2-10, 80804, Munchen, Germany; Emory University, Department of Psychiatry and Behavioral Sciences, 12 Executive Park Dr NE #200, Atlanta, GA 30329, USA.

PMID: 34952353 PMCID: PMC8715233 DOI: 10.1016/j.nicl.2021.102922

Abstract

BACKGROUND: Posttraumatic Stress Disorder (PTSD) is commonly treated with exposure-based cognitive therapies that are based on the principles of fear acquisition and extinction learning. Elevations in one of the major endocannabinoids (anandamide) either via inhibition of the primary degrading enzyme (fatty acid amide hydrolase; FAAH) or via a genetic variation in the FAAH gene (C385A; rs324420) has resulted in accelerated extinction learning and enhanced extinction recall among healthy adults. These results suggest that targeting FAAH may be a promising therapeutic approach for PTSD. However, these effects have not yet been comprehensively examined in a PTSD population.

METHODS: The current study examined whether genetic variation in the FAAH gene (CC [n = 49] vs AA/AC [n = 36] allele carriers) influences physiological (skin conductance), cognitive (threat expectancy), and neural (network and voxel-wise activation) indices of fear acquisition and extinction learning among a sample of adult women with PTSD (N = 85).

RESULTS: The physiological, cognitive, and neural signatures of fear acquisition and extinction learning varied as a function of whether or not individuals possess the FAAH C385A polymorphism. For instance, we report divergent responding between CC and AA/AC allele carriers to CS + vs CS- in limbic and striatum networks and overall greater activation throughout the task among AA/AC allele carriers in several regions [e.g., inferior frontal, middle frontal, parietal] that are highly consistent with a frontoparietal network involved in higher-order executive functions.

CONCLUSIONS: These results suggest that genetic variation within the FAAH gene influences physiological, cognitive, and neural signatures of fear learning in women with PTSD. In order to advance our understanding of the efficacy of FAAH inhibition as a treatment for PTSD, future clinical trials in this area should assess genetic variation in the FAAH gene in order to fully depict and differentiate the acute effects of a drug manipulation (FAAH inhibition) from more chronic (genetic) influences on fear extinction processes.

Copyright © 2021. Published by Elsevier Inc.

Keywords: Anandamide; Endocannabinoid system; Fatty acid amide hydrolase; Independent component analysis; Interpersonal violence; fMRI

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