Divergent effects of genetic variation in endocannabinoid signaling on human threat- and reward-related brain function.
Biol Psychiatry. 2009 Jul 1; 66(1):9-16
This article PDF usually requires a subscription to access but you can receive the PDF, at no cost, through a special arrangement between Springer Science+Business Media and Faculty of 1000 for our Faculty Members who act as reviewers. This PDF is provided to you only for the purposes of reviewing the article while you consider preparing a recommendation of the article for F1000Prime. Other than for this purpose you warrant that you will treat the PDF as confidential. Furthermore you warrant that you will not use the PDF for any other purpose, especially but not limited to forwarding, copying, selling, distributing it whether commercially or non-commercially and that you will not make it available on any website for any other purpose.
This study shows that a common functional polymorphism believed to affect endocannabinoid (eCB) signaling is associated with processing of threatening and rewarding stimuli. Individuals with the variant linked with higher synaptic eCB levels showed blunted neural response to threat and enhanced response to reward. These findings may have important implications regarding the role of eCB signaling in both anxiety and substance-use disorders.
The eCB system appears to be implicated in several psychiatric conditions including anxiety and substance-use disorders. Sources of individual variability in eCB signaling, and behaviors thought to be modulated by this system, are poorly understood. This study employed an imaging genetics approach to investigate associations between genes involved in eCB function and behavioral and neural responses to emotionally-salient stimuli. The authors studied a common polymorphism of the gene encoding fatty acid amide hydrolase (FAAH). FAAH degrades synaptic eCBs, and affects eCB signaling. One variant of the polymorphism (385A) is associated with reduced FAAH expression, and is, hence, believed to increase synaptic eCB levels compared with the non-mutated allele (385C). The authors examined threat processing, which is central to anxiety, and reward processing, which is associated with disorders of impulse control and substance abuse. They found that individuals with the 385A allele had blunted amygdala responses to threatening stimuli, and enhanced ventral striatum responses to a reward probe, compared to those who were homozygous for the 385C allele. These findings are consistent with the hypothesis that elevated eCB levels reduce anxiety and may also be involved in reward-related pathology, commonly found in addictive disorders. The study uses a powerful combination of genetic and imaging tools to investigate the mechanisms underlying anxiety and substance-use disorders, and supports the notion that the eCB system plays an important role. These findings may lead to potential pharmacotherapies targeting this system, and provide important information about genetic sources of individual variability that may contribute to cannabis use and other substance-use disorders.
de Wit H and Bedi G: F1000Prime Recommendation of [Hariri AR et al., Biol Psychiatry 2009, 66(1):9-16]. In F1000Prime, 20 May 2009; DOI: 10.3410/f.1160596.621969. F1000Prime.com/1160596#eval621969
F1000Prime Recommendations, Dissents and Comments for [Hariri AR et al., Biol Psychiatry 2009, 66(1):9-16]. In F1000Prime, 31 Jan 2015; F1000Prime.com/1160596
Get the most out of F1000Prime - attend a live online demonstration.
Please choose one of the following time zones:
Want to become an
has been added to your "Faculty I'm Following" page in MyF1000
Follow/Unfollow any Faculty via their recommendations, biography pages, or MyF1000
If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password.
The email address should be the one you originally registered with F1000.
You registered with F1000 via Google, so we cannot reset your password.
To sign in, please click here.
If you still need help with your Google account password, please click here.
You registered with F1000 via Facebook, so we cannot reset your password.
To sign in, please click here.
If you still need help with your Facebook account password, please click here.
We have sent an email to , please follow the instructions to reset your password.
If you don't receive this email, please check your spam filters and/or contact firstname.lastname@example.org.