Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation.
Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation.
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DOI：
10.1016/j.ynirp.2022.100094
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发表时间：
2022-06
期刊：
影响因子：
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通讯作者：
Boileau I
中科院分区：
文献类型：
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作者：
Green DG;Westwood DJ;Kim J;Best LM;Kish SJ;Tyndale RF;McCluskey T;Lobaugh NJ;Boileau I
临床前证据表明，增加主要内源性大麻素anandamide的水平可能通过其在杏仁核中的作用来降低焦虑和恐惧反应。在这里，我们使用神经影像学来检验假设，即低脂肪酸酰胺水解酶（FAAH），主要的anandamide分解代谢酶，与杏仁核对威胁的反应迟钝。28名健康的参与者完成了正电子发射断层扫描（PET），使用放射性示踪剂FAAH，[11 C]CURB，以及一个块设计的功能磁共振成像会议，在此期间，愤怒和恐惧的面孔意味着激活杏仁核。[11 C]杏仁核以及内侧前额叶皮层、扣带回和海马中的CURB结合与愤怒和恐惧面孔处理过程中的血氧水平依赖（BOLD）信号呈正相关（pFWE < 0.05）。我们的发现，杏仁核，内侧前额叶皮层，扣带回和海马体中FAAH水平较低与杏仁核对威胁性社会线索的反应减弱有关，这与人类的临床前和神经影像学研究一致，并表明FAAH参与调节人类的压力和焦虑。目前的神经影像学研究也支持FAAH抑制剂控制杏仁核过度活跃的潜在用途，杏仁核过度活跃已知参与焦虑和创伤相关疾病的病理生理学。
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. 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. [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). 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.