Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation
Background: Preclinical evidence suggests that increasing levels of the major endocannabinoid anandamide decreases anxiety and fear responses potentially through its effects in the amygdala. Here we used neuroimaging to test the hypothesis that lower fatty acid amide hydrolase (FAAH), the main catab...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-06-01
|
| Series: | Neuroimage: Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666956022000186 |
| _version_ | 1818208803175268352 |
|---|---|
| author | Duncan GJ. Green Duncan J. Westwood Jinhee Kim Laura M. Best Stephen J. Kish Rachel F. Tyndale Tina McCluskey Nancy J. Lobaugh Isabelle Boileau |
| author_facet | Duncan GJ. Green Duncan J. Westwood Jinhee Kim Laura M. Best Stephen J. Kish Rachel F. Tyndale Tina McCluskey Nancy J. Lobaugh Isabelle Boileau |
| author_sort | Duncan GJ. Green |
| collection | DOAJ |
| description | Background: Preclinical evidence suggests that increasing levels of the major endocannabinoid anandamide decreases anxiety and fear responses potentially through its effects in the amygdala. Here we used neuroimaging to test the hypothesis that lower fatty acid amide hydrolase (FAAH), the main catabolic enzyme for anandamide, is associated with a blunted amygdala response to threat. Methods: Twenty-eight healthy participants completed a positron emission tomography (PET) scan with the radiotracer for FAAH, [11C]CURB, as well as a block-design functional magnetic resonance imaging session during which angry and fearful faces meant to activate the amygdala were presented. Results: [11C]CURB binding in the amygdala as well as in the medial prefrontal cortex, cingulate and hippocampus correlated positively with blood-oxygen-level-dependent (BOLD) signal during processing of angry and fearful faces (pFWE < 0.05). Conclusion: Our finding that lower levels of FAAH in amygdala, medial prefrontal cortex, cingulate and hippocampus was associated with a dampened amygdala response to a threatening social cue aligns with preclinical and neuroimaging studies in humans and suggests the involvement of FAAH in modulating stress and anxiety in humans. The current neuroimaging study also lends support for the potential use of FAAH inhibitors to control amygdala hyperactivity, which is known to be involved in the pathophysiology of anxiety and trauma-related disorders. |
| first_indexed | 2024-12-12T04:50:37Z |
| format | Article |
| id | doaj.art-36a7df305f684147a2ca3d03138fdb2d |
| institution | Directory Open Access Journal |
| issn | 2666-9560 |
| language | English |
| last_indexed | 2024-12-12T04:50:37Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neuroimage: Reports |
| spelling | doaj.art-36a7df305f684147a2ca3d03138fdb2d2022-12-22T00:37:28ZengElsevierNeuroimage: Reports2666-95602022-06-0122100094Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activationDuncan GJ. Green0Duncan J. Westwood1Jinhee Kim2Laura M. Best3Stephen J. Kish4Rachel F. Tyndale5Tina McCluskey6Nancy J. Lobaugh7Isabelle Boileau8Addiction Imaging Research Group, Canada; Faculty of Medicine, University of Toronto, Toronto, CanadaAddiction Imaging Research Group, CanadaDepartments of Psychiatry, Canada; Department of Psychology, Korea University, Republic of KoreaAddiction Imaging Research Group, Canada; Faculty of Medicine, University of Toronto, Toronto, CanadaHuman Brain Lab, Canada; Campbell Family Mental Health Research Institute, Canada; Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada; Departments of Psychiatry, Canada; Pharmacology & Toxicology, Canada; Faculty of Medicine, University of Toronto, Toronto, CanadaCampbell Family Mental Health Research Institute, Canada; Departments of Psychiatry, Canada; Pharmacology & Toxicology, CanadaHuman Brain Lab, Canada; Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, CanadaCampbell Family Mental Health Research Institute, Canada; Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada; Faculty of Medicine, University of Toronto, Toronto, CanadaAddiction Imaging Research Group, Canada; Campbell Family Mental Health Research Institute, Canada; Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada; Departments of Psychiatry, Canada; Faculty of Medicine, University of Toronto, Toronto, Canada; Corresponding author. Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.Background: Preclinical evidence suggests that increasing levels of the major endocannabinoid anandamide decreases anxiety and fear responses potentially through its effects in the amygdala. Here we used neuroimaging to test the hypothesis that lower fatty acid amide hydrolase (FAAH), the main catabolic enzyme for anandamide, is associated with a blunted amygdala response to threat. Methods: Twenty-eight healthy participants completed a positron emission tomography (PET) scan with the radiotracer for FAAH, [11C]CURB, as well as a block-design functional magnetic resonance imaging session during which angry and fearful faces meant to activate the amygdala were presented. Results: [11C]CURB binding in the amygdala as well as in the medial prefrontal cortex, cingulate and hippocampus correlated positively with blood-oxygen-level-dependent (BOLD) signal during processing of angry and fearful faces (pFWE < 0.05). Conclusion: Our finding that lower levels of FAAH in amygdala, medial prefrontal cortex, cingulate and hippocampus was associated with a dampened amygdala response to a threatening social cue aligns with preclinical and neuroimaging studies in humans and suggests the involvement of FAAH in modulating stress and anxiety in humans. The current neuroimaging study also lends support for the potential use of FAAH inhibitors to control amygdala hyperactivity, which is known to be involved in the pathophysiology of anxiety and trauma-related disorders.http://www.sciencedirect.com/science/article/pii/S2666956022000186FAAHfMRI BOLDPET [11C]CURBThreatPerceptual face taskAmygdala |
| spellingShingle | Duncan GJ. Green Duncan J. Westwood Jinhee Kim Laura M. Best Stephen J. Kish Rachel F. Tyndale Tina McCluskey Nancy J. Lobaugh Isabelle Boileau Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation Neuroimage: Reports FAAH fMRI BOLD PET [11C]CURB Threat Perceptual face task Amygdala |
| title | Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation |
| title_full | Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation |
| title_fullStr | Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation |
| title_full_unstemmed | Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation |
| title_short | Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation |
| title_sort | fatty acid amide hydrolase levels in brain linked with threat related amygdala activation |
| topic | FAAH fMRI BOLD PET [11C]CURB Threat Perceptual face task Amygdala |
| url | http://www.sciencedirect.com/science/article/pii/S2666956022000186 |
| work_keys_str_mv | AT duncangjgreen fattyacidamidehydrolaselevelsinbrainlinkedwiththreatrelatedamygdalaactivation AT duncanjwestwood fattyacidamidehydrolaselevelsinbrainlinkedwiththreatrelatedamygdalaactivation AT jinheekim fattyacidamidehydrolaselevelsinbrainlinkedwiththreatrelatedamygdalaactivation AT laurambest fattyacidamidehydrolaselevelsinbrainlinkedwiththreatrelatedamygdalaactivation AT stephenjkish fattyacidamidehydrolaselevelsinbrainlinkedwiththreatrelatedamygdalaactivation AT rachelftyndale fattyacidamidehydrolaselevelsinbrainlinkedwiththreatrelatedamygdalaactivation AT tinamccluskey fattyacidamidehydrolaselevelsinbrainlinkedwiththreatrelatedamygdalaactivation AT nancyjlobaugh fattyacidamidehydrolaselevelsinbrainlinkedwiththreatrelatedamygdalaactivation AT isabelleboileau fattyacidamidehydrolaselevelsinbrainlinkedwiththreatrelatedamygdalaactivation |