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. 2022 Jun;2(2):100094.
doi: 10.1016/j.ynirp.2022.100094.

Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation

Duncan Gj Green  1   2 , Duncan J Westwood  1 , Jinhee Kim  3   4 , Laura M Best  1   2 , Stephen J Kish  5   6   7   3   8   2 , Rachel F Tyndale  6   3   8 , Tina McCluskey  5   7 , Nancy J Lobaugh  6   7   2 , Isabelle Boileau  1   6   7   3   2
Affiliations

Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation

Duncan Gj Green et al. Neuroimage Rep. 2022 Jun.

Abstract

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.

Keywords: Amygdala; FAAH; PET [11C]CURB; Perceptual face task; Threat; fMRI BOLD.

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Figures

Fig. 1
Fig. 1
Amygdala Activation to emotional faces compared to shapes. Amygdala BOLD reactivity was increased in response to emotional faces vs shapes (R, 30, −4, −23, k = 30; L, −27, −7, −20, k = 35, All p FWE small volume corrected < 0.05).
Fig. 2
Fig. 2
Correlation between amygdala BOLD reactivity and amygdala [11C]CURB. Amygdala BOLD reactivity in response to emotional faces was positively correlated with [11C]CURB binding (R, 27, −7, −16, k = 17, r = 0.51 pFWE small volume corrected < 0.01, z = 2.43; L, −18, −7, −16, k = 8, r = 0.39, pFWE small volume corrected = 0.03, z = 1.74).
See this image and copyright information in PMC

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