PMID- 33614866
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210223
IS  - 2352-2895 (Print)
IS  - 2352-2895 (Electronic)
IS  - 2352-2895 (Linking)
VI  - 14
DP  - 2021 May
TI  - Circulating endocannabinoids and prospective risk for depression in trauma-injury 
      survivors.
PG  - 100304
LID - 10.1016/j.ynstr.2021.100304 [doi]
LID - 100304
AB  - 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 (beta = 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 (beta = 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.
CI  - (c) 2021 The Authors.
FAU - Fitzgerald, Jacklynn M
AU  - Fitzgerald JM
AD  - Marquette University, Department of Psychology, Milwaukee, WI, USA.
FAU - Chesney, Samantha A
AU  - Chesney SA
AD  - Froedtert Memorial Lutheran Hospital - Neurological Rehabilitation Services, 
      Milwaukee, WI, USA.
FAU - Lee, Tara Sander
AU  - Lee TS
AD  - Charlotte Lozier Institute, Arlington, VA, USA.
FAU - Brasel, Karen
AU  - Brasel K
AD  - Oregon Health & Science University, Portland, OR, USA.
FAU - Larson, Christine L
AU  - Larson CL
AD  - University of Wisconsin - Milwaukee, Department of Psychology, Milwaukee, WI, 
      USA.
FAU - Hillard, Cecilia J
AU  - Hillard CJ
AD  - Medical College of Wisconsin, Neuroscience Research Center and Department of 
      Pharmacology and Toxicology, Milwaukee, WI, USA.
FAU - deRoon-Cassini, Terri A
AU  - deRoon-Cassini TA
AD  - Medical College of Wisconsin, Department of Surgery, Division of Trauma & Acute 
      Care Surgery, Milwaukee, WI, USA.
LA  - eng
PT  - Journal Article
DEP - 20210204
PL  - United States
TA  - Neurobiol Stress
JT  - Neurobiology of stress
JID - 101643409
PMC - PMC7876629
OTO - NOTNLM
OT  - Depression
OT  - Endocannabinoids
OT  - Genotype
OT  - Injuries
OT  - Trauma
COIS- This work was supported by the National Institute of Mental Health (NIMH R21 
      MH102838; deRoon-Cassini, Hillard). This funding source had no direct involvement 
      in the design, collection, analysis, and writing of this report. Drs. Fitzgerald, 
      Chesney, Brasel, and Larson have no financial disclosures to report and no 
      authors have any conflicts of interest to report.
EDAT- 2021/02/23 06:00
MHDA- 2021/02/23 06:01
PMCR- 2021/02/04
CRDT- 2021/02/22 05:58
PHST- 2020/08/17 00:00 [received]
PHST- 2021/01/19 00:00 [revised]
PHST- 2021/01/30 00:00 [accepted]
PHST- 2021/02/22 05:58 [entrez]
PHST- 2021/02/23 06:00 [pubmed]
PHST- 2021/02/23 06:01 [medline]
PHST- 2021/02/04 00:00 [pmc-release]
AID - S2352-2895(21)00012-6 [pii]
AID - 100304 [pii]
AID - 10.1016/j.ynstr.2021.100304 [doi]
PST - epublish
SO  - Neurobiol Stress. 2021 Feb 4;14:100304. doi: 10.1016/j.ynstr.2021.100304. 
      eCollection 2021 May.