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FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence. | LitMetric

AI Article Synopsis

  • A common genetic variation (C385A) in the FAAH gene is linked to reduced distress responses among healthy individuals, but its effects on psychiatric disorders are unclear.
  • In a study involving 49 patients with PTSD and alcohol dependence, researchers assessed how this genetic variation impacted stress responses and endocannabinoid levels during stress challenges.
  • Results showed that FAAH C385A carriers had higher anandamide levels and lower anxiety during stress challenges, suggesting that targeting the endocannabinoid pathway could be a potential strategy for treating stress-related disorders.

Article Abstract

Background: A common single nucleotide polymorphism (C385A) in the human fatty acid amide hydrolase (FAAH) gene has been associated with decreased distress responses in healthy volunteers, but its role in psychiatric disorders remains unknown. Here, we obtained genotypes and carried out a secondary analysis of subjects from a trial of comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD). We evaluated the effects of C385A variation on behavioral and biochemical biomarkers of distress responses.

Methods: Forty-nine patients with PTSD and AD were admitted for 4 weeks to an experimental medicine unit at the National Institutes of Health Clinical Center. Following detoxification, stress reactivity and peripheral endocannabinoid (eCB) levels were assessed in response to a challenge session using personalized auditory guided imagery. Over the course of the study, subjects were also evaluated for changes in PTSD symptom severity.

Results: FAAH C385A allele carriers showed a marked increase in serum anandamide levels at baseline and throughout the stress challenge procedure compared with C allele homozygotes, while levels of eCBs primarily metabolized through other enzymatic activity, such as 2-arachidonoylglycerol, did not differ between genotype groups. FAAH C385A carriers also had decreased subjective anxiety responses to the stress challenge. Similar effects of FAAH C385A genotype were found at the level of clinical PTSD symptom severity, in particular in the arousal domain.

Conclusions: This is to our knowledge the first study showing that FAAH C385A variation modulates stress responses in subjects with disorders characterized by increased stress reactivity. These findings point to the eCB pathway as a promising target for future antistress therapeutics.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748341PMC
http://dx.doi.org/10.1111/acer.13210DOI Listing

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