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Biol Psychiatry. 2009 Jul 1;66(1):9-16. doi: 10.1016/j.biopsych.2008.10.047. Epub 2008 Dec 21.

Divergent effects of genetic variation in endocannabinoid signaling on human threat- and reward-related brain function.

Author information

  • 1Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. haririar@upmc.edu

Abstract

BACKGROUND:

Fatty acid amide hydrolase (FAAH) is a key enzyme in regulating endocannabinoid (eCB) signaling. A common single nucleotide polymorphism (C385A) in the human FAAH gene has been associated with increased risk for addiction and obesity.

METHODS:

Using imaging genetics in 82 healthy adult volunteers, we examined the effects of FAAH C385A on threat- and reward-related human brain function.

RESULTS:

Carriers of FAAH 385A, associated with reduced enzyme and possibly increased eCB signaling, had decreased threat-related amygdala reactivity but increased reward-related ventral striatal reactivity in comparison with C385 homozygotes. Similarly divergent effects of FAAH C385A genotype were manifest at the level of brain-behavior relationships. The 385A carriers showed decreased correlation between amygdala reactivity and trait anxiety but increased correlation between ventral striatal reactivity and delay discounting, an index of impulsivity.

CONCLUSIONS:

Our results parallel pharmacologic and genetic dissection of eCB signaling, are consistent with the psychotropic effects of Delta(9)-tetrahydrocannabinol, and highlight specific neural mechanisms through which variability in eCB signaling impacts complex behavioral processes related to risk for addiction and obesity.

PMID:
19103437
[PubMed - indexed for MEDLINE]
PMCID:
PMC3215587
Free PMC Article

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