Trauma and the Genetics of the Endocannabinoid System

描述(申请人提供)：创伤后应激障碍(PTSD)是一种普遍的和衰弱的综合征，发生在一些但不是所有暴露在创伤事件中的个人。创伤后应激障碍的获得取决于心理和遗传因素。一些研究表明，神经递质的内源性大麻素系统可能通过影响涉及恐惧、学习和动机的神经系统，在创伤后应激障碍的病因中发挥作用。我们假设，在创伤暴露的个体中，内源性大麻素基因的变异与创伤后应激障碍的风险改变有关。这个项目将研究一个由七个主要基因组成的系统，该系统对内源性大麻素系统的功能至关重要。由于内源性大麻素是按需快速合成和代谢的，因此合成/代谢酶或受体内的功能变化可能会 预示着后果。这样的后果可能会反映在精神疾病的风险上。我们将研究与合成内源性大麻素[NAPE-PLD(N-花生甲酰磷脂酰乙醇胺水解型磷脂酶D)，C11orf11(染色体11开放阅读框架11又称为二酰基甘油脂肪酶-α)，PTPN22(蛋白质酪氨酸磷酸酶，非受体22型)]；对内源性大麻素的反应[CNR1(大麻素受体1又称CB1)，CNR2(大麻素受体2又称为CB2)]以及内源性大麻素的降解[FAAH(脂肪酸水解酶)，MGLL(单甘油酯脂酶)]--以下统称为“内源性大麻素系统基因”(ESGs)的基因。我们将对从市中心普通医疗诊所招募的1000多名受试者(主要是非裔美国人)进行严重创伤样本的分析。这个项目将检验这样的假设，即ESG的多态与PTSD诊断和症状严重程度的不同风险相关。

DESCRIPTION (provided by applicant): Post-traumatic stress disorder (PTSD) is a prevalent and debilitating syndrome that occurs in some, but not all, individuals exposed to traumatic events. Acquisition of PTSD is contingent on psychological as well as genetic factors. Several lines of research suggest that the endocannabinoid system of neurotransmitters may have a role in the etiology of PTSD through effects on the neural systems involved in fear learning and motivation. We hypothesize that in trauma-exposed individuals, variants of endocannabinoid genes are associated with altered risk for PTSD. This project will investigate a system of seven major genes important for function of the endocannabinoid system. Because endocannabinoids are rapidly synthesized on demand and metabolized, functional changes within synthesizing/metabolizing enzymes or receptors may have signaling consequences. Such consequences may be reflected in risk for psychiatric illness. We will examine genes involved in the synthesis of endocannabinoids [NAPE-PLD (N-arachidonoyl phosphatidylethanolamine-hydrolyzing Phospholipase D), C11orf11 (chromosome 11 open reading frame 11 aka diacylglycerol lipase-alpha), PTPN22 (protein tyrosine phosphatase, non-receptor type 22)]; response to endocannabinoids [CNR1 (cannabinoid receptor 1 aka CB1), CNR2 (cannabinoid receptor 2 aka CB2)], and degradation of endocannabinoids [FAAH (fatty acid amide hydrolase), MGLL (monoglyceride lipase)]-referred to collectively hereafter as "endocannabinoid system genes" (ESGs). We will perform this analysis in a heavily traumatized sample of over 1000 subjects (predominantly African-American) recruited from an inner-city general medical clinic. This project will test the hypothesis that polymorphisms of the ESGs are associated with differential risk for PTSD diagnosis and symptom severity.