Circulating endocannabinoids and genetic polymorphisms as predictors of posttraumatic stress disorder symptom severity: heterogeneity in a community-based cohort

Abstract

The endocannabinoid signaling system (ECSS) regulates fear and anxiety. While ECSS hypoactivity can contribute to symptoms of established post-traumatic stress disorder (PTSD), the role of the ECSS in PTSD development following trauma is unknown. A prospective, longitudinal cohort study of 170 individuals (47% non-Hispanic Caucasian and 70% male) treated at a level 1 trauma center for traumatic injury was carried out. PTSD symptom assessments and blood were obtained during hospitalization and at follow-up (6–8 months post injury). Serum concentrations of the endocannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) were determined at both time points and selected genetic polymorphisms in endocannabinoid genes, including rs324420 in fatty acid amide hydrolase, were assessed. For the entire sample, serum concentrations of AEA at hospitalization were significantly higher in those diagnosed with PTSD at follow-up (p = 0.030). Serum concentrations of 2-AG were significantly, positively correlated with PTSD symptom severity at follow-up only in minorities (p = 0.014). Minority participants (mostly Black/African American) also demonstrated significant, negative correlations between serum AEA concentrations and PTSD symptom severity both measured at hospitalization (p = 0.015). The A/A genotype at rs324420 was associated with significantly higher PTSD symptom severity (p = 0.025) and occurred exclusively in the Black participants. Collectively, these results are contrary to our hypothesis and find positive associations between circulating endocannabinoids and risk for PTSD. Minority status is an important modulator of the association between endocannabinoids and risk for PTSD, suggesting that the ECSS contributes to risk most significantly in these individuals and the contextual factors related to these findings should be further explored.

Machine learning prediction of posttraumatic stress disorder trajectories following traumatic injury: Identification and validation in two independent samples

“…PTSD) but rather underscores the disparities in trauma exposure and injury prevalence among racial and ethnic groups (Alegría et al., 2013). We also found that circulating concentrations of endocannabinoids (i.e., AEA and 2‐AG) at the time of injury were predictive of PTSD risk, which confirms prior work demonstrating high correlations between endocannabinoid levels and trauma outcomes (deRoon‐Cassini et al., 2022; Fitzgerald et al., 2021). Although the inclusion of stress‐related biomarkers in this study (i.e., cortisol and endocannabinoids) is novel, and the findings support the role that these biomarkers have in prediction, the complex nature of these variables makes the findings preliminary.…”

Serum Concentrations of the Endocannabinoid, 2-Arachidonoylglycerol, in the Peri-Trauma Period Are Positively Associated with Chronic Pain Months Later

“…Previous studies in humans have found that AEA concentrations are more likely to be associated with anxiety while 2-AG is more likely to be associated with depression [ 56 , 57 ]. Interestingly, 2-AG concentrations at hospitalization were also associated with increased risk for depression at follow-up [ 32 ], while AEA concentrations at hospitalization were associated with risk for the development of chronic PTSD [ 33 ] in the participants of this study.…”

“…The Institutional Review Board (IRB) at the Medical College of Wisconsin approved all study procedures (PRO00022827, approved on 3 May 2019) and participants were monetarily compensated for their time. Participants in this study were subjects of a prospective, exploratory, longitudinal cohort study entitled “Study on Trauma and Resilience (STAR).” We have previously reported some demographic and clinical data and the relationship between endocannabinoids and depression [ 32 ] and risk for post-traumatic stress disorder (PTSD) [ 33 ] in the same cohort. Two hundred eighty participants were recruited and consented at the time of injury in the parent study; 147 completed the follow-up pain assessments and blood draw and are included in these analyses.…”

Life threat during assaultive trauma: Critical posttraumatic stress disorder risk factors for injured patients

“…A total of 356 adult participants were recruited from the trauma service of a level 1 trauma center in a Midwestern, midsized city. Data were pooled from two studies that examined outcomes (e.g., psychological and biological) of traumatic injury (for full description of methods 3,30 . This study conforms with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines, and a complete checklist has been uploaded as Supplemental Digital Content (see Supplementary Table 1, http://links.lww.com/TA/C316, for Strengthening the Reporting of Observational Studies in Epidemiology checklist).…”