Abstract
Background
Preclinical models reveal that stress-induced amygdala activity and impairment in
fear extinction reflect reductions in anandamide driven by corticotropin-releasing
factor receptor type 1 (CRF1) potentiation of the anandamide catabolic enzyme fatty acid amide hydrolase.
Methods
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 CRF1 (CRHR1 rs110402) signaling modulate amygdala function and anxiety disorder diagnosis.
Results
Analyses revealed that individuals with a genetic background predicting relatively
high anandamide and CRF1 signaling exhibited blunted basolateral amygdala habituation, which further mediated
increased risk for anxiety disorders among these same individuals.
Conclusions
The convergence of preclinical and clinical data suggests that interactions between
anandamide and CRF1 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.
Keywords
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Article info
Publication history
Published online: January 04, 2016
Accepted:
December 22,
2015
Received in revised form:
December 22,
2015
Received:
October 26,
2015
Identification
Copyright
© 2016 Society of Biological Psychiatry.
