The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD
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 enzym...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-01-01
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| Series: | NeuroImage: Clinical |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158221003661 |
| _version_ | 1818286658034860032 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kevin M. Crombie |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T01:28:05Z |
| format | Article |
| id | doaj.art-32911662f46244df87aa4e953dd41eaa |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-12-13T01:28:05Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-32911662f46244df87aa4e953dd41eaa2022-12-22T00:04:04ZengElsevierNeuroImage: Clinical2213-15822022-01-0133102922The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSDKevin M. Crombie0Anthony A. Privratsky1Chloe M. Schomaker2Mickela Heilicher3Marisa C. Ross4Anneliis Sartin-Tarm5Kyrie Sellnow6Elisabeth B. Binder7G. Andrew James8Josh M. Cisler9The University of Texas at Austin, Department of Psychiatry and Behavioral Sciences, Health Discovery Building, 1601 Trinity St., Building B, Austin, TX 78712, USA; Corresponding author.University of Arkansas for Medical Sciences, Brain Imaging Research Center, 4301 W. Markham Street #554, Little Rock, AR 72205, USAThe University of Texas at Austin, Department of Psychiatry and Behavioral Sciences, Health Discovery Building, 1601 Trinity St., Building B, Austin, TX 78712, USAUniversity of Wisconsin - Madison, Department of Psychiatry, 6001 Research Park Boulevard, Madison, WI 53719-1176608-262-6375, USAUniversity of Wisconsin - Madison, Department of Psychiatry, 6001 Research Park Boulevard, Madison, WI 53719-1176608-262-6375, USAUniversity of Wisconsin - Madison, Department of Psychiatry, 6001 Research Park Boulevard, Madison, WI 53719-1176608-262-6375, USAUniversity of Wisconsin - Madison, Department of Psychiatry, 6001 Research Park Boulevard, Madison, WI 53719-1176608-262-6375, USAMax 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, USAUniversity of Arkansas for Medical Sciences, Brain Imaging Research Center, 4301 W. Markham Street #554, Little Rock, AR 72205, USAThe University of Texas at Austin, Department of Psychiatry and Behavioral Sciences, Health Discovery Building, 1601 Trinity St., Building B, Austin, TX 78712, USABackground: 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.http://www.sciencedirect.com/science/article/pii/S2213158221003661Endocannabinoid systemFatty acid amide hydrolasefMRIIndependent component analysisInterpersonal violenceAnandamide |
| spellingShingle | 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 The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD NeuroImage: Clinical Endocannabinoid system Fatty acid amide hydrolase fMRI Independent component analysis Interpersonal violence Anandamide |
| title | The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD |
| title_full | The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD |
| title_fullStr | The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD |
| title_full_unstemmed | The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD |
| title_short | The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD |
| title_sort | influence of faah genetic variation on physiological cognitive and neural signatures of fear acquisition and extinction learning in women with ptsd |
| topic | Endocannabinoid system Fatty acid amide hydrolase fMRI Independent component analysis Interpersonal violence Anandamide |
| url | http://www.sciencedirect.com/science/article/pii/S2213158221003661 |
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