Predicting who develops Posttraumatic Stress Disorder (PTSD) after a traumatic injury has remained elusive. The long-term research goal is to identify the biological mechanisms involved in maintenance of or protection against the development of chronic PTSD. Emerging research suggests that the endocannabinoid signaling system (ECSS) modulates the stress response to reduce anxiety. The ECSS consists of the CB1 cannabinoid receptor (CB1R) and two endogenous ligands (N- arachidonylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG). The objective of this proposal is to determine the involvement of the ECSS in acute and long-term psychological distress following traumatic injury. The central hypothesis is that high endocannabinoid signaling increases the likelihood of resilience following trauma.
The specific aims of the proposed project are to: 1) Characterize the circulating endocannabinoid signaling response (AEA, 2-AG) specific to traumatic injury (acute stressor) for chronic PTSD and resilience trajectories;2) Determine the genotype variants of CNR1 and fatty acid amide hydrolase (FAAH) across chronic and resilient trajectories of PTSD symptom levels after traumatic injury. The ECSS engages the central (brain) nervous systems potentially impacting the fear conditioned response that occurs during a trauma that leads to the development of PTSD. Based on basic science research, greater activation of the ECSS after a traumatic effect may prove to be protective, leading to greater resilience after trauma, and ultimately helping to reduce the significant burden of PTSD. This study proposes a longitudinal prospective cohort study of single incident assaultive trauma survivors admitted to a level 1 trauma center for medical care. Participants will receive two blood draws in the hospital, a structured clinical interview to assess PTSD symptom severity, and a cheek swab for analysis of genetic material. At six months posttrauma, participants will return for an additional lab draw and the same structured clinical interview to assess for PTSD. Standardized laboratory techniques will be used to assess the serum for 2-AG and AEA, and standard techniques will evaluate the genotype variants of CNR1 and FAAH. Statistical analysis will compare endocannabinoid content for resilience and chronic PTSD, and will assess the genotype variants of CNR1 and FAAH for these two groups.
Posttrauamtic stress disorder (PTSD) has been shown to negatively impact physical health and increase somatic complaints with more frequent physician visits, is associated with high rates of psychiatric and medical comorbidity, high utilization of health resources, and elevated functional impairment. Once PTSD symptoms are chronic the individual may continue to suffer for years in the absence of appropriate treatment. PTSD constitutes a significant public health burden and this project aims to identify biological mechanisms implicated in the development of PTSD in order to deliver early intervention to those at risk for long-term distress.
|Hillard, Cecilia J (2015) The Endocannabinoid Signaling System in the CNS: A Primer. Int Rev Neurobiol 125:1-47|
|Lutz, Beat; Marsicano, Giovanni; Maldonado, Rafael et al. (2015) The endocannabinoid system in guarding against fear, anxiety and stress. Nat Rev Neurosci 16:705-18|