التفاصيل البيبلوغرافية
العنوان: |
Divergent Effects of Genetic Variation in Endocannabinoid Signaling on Human Threat- and Reward-Related Brain Function |
المؤلفون: |
Hariri, Ahmad R.1,2 haririar@upmc.edu, Gorka, Adam2, Hyde, Luke W.2, Kimak, Mark3, Halder, Indrani1, Ducci, Francesca4, Ferrell, Robert E.3, Goldman, David4, Manuck, Stephen B.1,2 |
المصدر: |
Biological Psychiatry. Jul2009, Vol. 66 Issue 1, p9-16. 8p. |
مصطلحات موضوعية: |
*BIOLOGICAL divergence, *HUMAN genetic variation, *CANNABINOIDS, *CELLULAR signal transduction, *CELL physiology, *THREAT (Psychology), *REWARD (Psychology), *ENZYME regulation |
مستخلص: |
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 Δ9-tetrahydrocannabinol, and highlight specific neural mechanisms through which variability in eCB signaling impacts complex behavioral processes related to risk for addiction and obesity. [Copyright &y& Elsevier] |
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