Role of ECS in Resilience & Psychopathology After Trauma

描述（由申请人提供）：预测谁会在创伤后患上创伤后应激障碍（PTSD）仍然是难以捉摸的。长期研究的目标是确定参与维持或防止慢性创伤后应激障碍发展的生物学机制。新兴研究表明，内源性大麻素信号系统（ECSS）调节压力反应，以减少焦虑。ECSS由CB1大麻素受体（CB1R）和两种内源性配体（N-花生四烯醇乙醇胺（AEA）和2-花生四烯醇甘油（2-AG））组成。本提案的目的是确定ECSS在创伤性损伤后急性和长期心理困扰中的作用。中心假设是高内源性大麻素信号增加创伤后恢复的可能性。该项目的具体目标是：1)表征慢性创伤后应激障碍和恢复轨迹中创伤性损伤（急性应激源）特有的循环内源性大麻素信号反应（AEA, 2-AG）；2)确定CNR1和脂肪酸酰胺水解酶（FAAH）在创伤后PTSD症状水平的慢性和弹性轨迹中的基因型变异。ECSS涉及中枢（大脑）神经系统，可能影响创伤期间发生的恐惧条件反射，从而导致PTSD的发展。根据基础科学研究，创伤后ECSS的更大激活可能被证明具有保护作用，导致创伤后更大的恢复力，并最终有助于减轻创伤后应激障碍的重大负担。本研究提出了一项纵向前瞻性队列研究，研究对象是在一级创伤中心接受医疗护理的单次攻击创伤幸存者。参与者将在医院接受两次抽血，一次结构化的临床访谈以评估创伤后应激障碍症状的严重程度，以及一次用于分析遗传物质的口腔拭子。在创伤后六个月，参与者将返回进行额外的实验室抽签和

DESCRIPTION (provided by applicant): 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.