Interactions Between Anandamide and Corticotropin-Releasing Factor Signaling Modulate Human Amygdala Function and Risk for Anxiety Disorders: An Imaging Genetics Strategy for Modeling Molecular Interactions.
Interactions Between Anandamide and Corticotropin-Releasing Factor Signaling Modulate Human Amygdala Function and Risk for Anxiety Disorders: An Imaging Genetics Strategy for Modeling Molecular Interactions.
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DOI：
10.1016/j.biopsych.2015.12.021
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发表时间：
2016-09-01
影响因子：
10.6
通讯作者：
Hariri AR
中科院分区：
文献类型：
--
作者：
Demers CH;Drabant Conley E;Bogdan R;Hariri AR
Preclinical models reveal that stress-induced amygdala activity and impairment in fear extinction reflects reductions in anandamide driven by corticotropin-releasing hormone receptor type 1 (CRHR1) potentiation of the anandamide catabolic enzyme fatty acid amide hydrolase (FAAH). Here we provide clinical translation for the importance of these molecular interactions using an imaging genetics strategy to examine whether interactions between genetic polymorphisms associated with differential anandamide (FAAH rs324420) and CRHR1 (CRHR1 rs110402) signaling modulate amygdala function and anxiety disorder diagnosis. Analyses revealed that individuals with a genetic background predicting relatively high anandamide and CRHR1 signaling exhibited blunted basolateral amygdala habituation, which further mediated increased risk for anxiety disorders amongst these same individuals. The convergence of preclinical and clinical data suggests that interactions between anandamide and CRHR1 represent a fundamental molecular mechanism regulating amygdala function and anxiety. Our results further highlight the potential of imaging genetics to powerfully translate complex preclinical findings to clinically meaningful human phenotypes.
