Circulating endocannabinoids and prospective risk for depression in trauma-injury survivors

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