FAAH genotype, CRFR1 genotype, and cortisol interact to predict anxiety in an aging, rural Hispanic population: A Project FRONTIER study

The neurophysiological underpinnings involved in susceptibility to and maintenance of anxiety are not entirely known. However, two stress-responsive systems, the hypothalamic-pituitary-adrenal axis and the endocannabinoid system, may interact in anxiety. Here, we examine the relationship between FAAH genotype, CRFR1 genotype, baseline cortisol, and state anxiety in a rural adult population using data from Project FRONTIER. We predicted that FAAH A (AA and AC vs CC; rs324420) and three CRFR1 SNP minor alleles (rs7209436 C→ T [minor allele]; rs110402, G → A [minor]; and rs242924 G→ T [minor]), would interact to predict low baseline cortisol and low state anxiety scores. We found partial support for our prediction. In CRFR1 minor carriers, the FAAH AA or AC (vs. CC) genotype was associated with higher cortisol and with lower anxiety. In CRFR1 non-minors, those with FAAH AA or AC (vs. CC) showed decreased cortisol and higher anxiety. These results suggest that FAAH CC genotype only conveys risk for anxiety in individuals who are also carriers of the CRFR1 minor combination. FAAH genotype was significantly associated with baseline cortisol but was not independently associated with anxiety. Contrary to our predictions, baseline cortisol was negatively associated with anxiety. Lastly, we did not find any independent relationships between any of our SNPs and baseline cortisol or anxiety. These data suggest FAAH and cortisol interact to predict state anxiety, but that the relationship depends on CRFR1 genotype. The Project FRONTIER dataset is supported by Texas Tech University Health Sciences Center Garrison Institute on Aging. Keywords: FAAH, CRFR1, Anxiety, Cortisol, Project FRONTIER