Circulating Endocannabinoids and Prospective Risk for Depression in Trauma-injury Survivors

Authors

Jacklynn M. Fitzgerald, Marquette UniversityFollow
Samantha Chesney, Froedtert Memorial Lutheran Hospital
Tara Sander Lee, Charlotte Lozier Institute
Karen J. Brasel, Oregon Health and Science University
Christine L. Larson, University of Wisconsin - Milwaukee
Cecilia J. Hillard, Medical College of Wisconsin
Terri A deRoon-Cassini, Medical College of Wisconsin

Document Type

Article

Publication Date

5-2021

Publisher

Elsevier

Source Publication

Neurobiology of Stress

Source ISSN

2352-2895

Abstract

Biological mechanisms associated with response to trauma may impact risk for depression. One such mechanism is endocannabinoid signaling (eCB), a neuromodulatory system comprised of the CB1 subtype of cannabinoid receptors (CB1R), encoded by the CNR1 gene, and two primary endogenous ligands: 2-arachidonoylglycerol (2-AG) and N-arachidonylethanolamine (AEA), hydrolyzed by monoacylglycerol lipase (gene name MGLL) and fatty acid amide hydrolase (gene name FAAH). Preclinical data suggest that eCB/CB1R signaling acts as a stress buffer and its loss or suppression increases depression-like behaviors. We examined circulating concentrations of the eCBs (2-AG and AEA) days and six months after a traumatic injury as a marker of eCB/CB1R signaling and as predictors of Center for Epidemiologic Studies of Depression Scale-Revised [CESD-R] scores as a measure of depression severity six months after injury. We also explored associations of CNR1, FAAH, and MGLL genetic variance with depression severity at six months. Results from hierarchical multiple linear regressions showed that higher 2-AG serum concentrations after trauma predicted greater depression at six months (β = 0.23, p = 0.007); neither AEA after trauma, nor 2-AG and AEA at six months were significant predictors (p's > 0.305). Carriers of minor allele for the putative single nucleotide polymorphism in the CNR1 gene rs806371 (β = 0.19, p = 0.024) experienced greater depression at six months. These data suggest that the eCB signaling system is highly activated following trauma and that eCB/CB1R activity contributes to long-term depression risk.

Comments

Published version. Neurobiology of Stress, Vol. 14 (May 2021): 100304. DOI. © 2021 Elsevier. Used with permission.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Fitzgerald, Jacklynn M.; Chesney, Samantha; Lee, Tara Sander; Brasel, Karen J.; Larson, Christine L.; Hillard, Cecilia J.; and deRoon-Cassini, Terri A, "Circulating Endocannabinoids and Prospective Risk for Depression in Trauma-injury Survivors" (2021). Psychology Faculty Research and Publications. 498.
https://epublications.marquette.edu/psych_fac/498