PROSPECTIVE NEUROBIOLOGICAL STUDY OF PTSD

这一相互竞争的延续建议的主要目标是：a.）到 首次连续测量下丘脑-垂体- 肾上腺（HPA）轴和交感神经系统（SNS）的活动，在一个 大量的心理创伤者样本， 创伤性事件的后果和随访中; B.）评价 HPA和SNS反应模式的时间过程与 创伤后应激障碍（PTSD）的发展;以及c.）审查 SNS和HPA轴在PTSD中可能的相互作用 发病机制 HPA和SNS测量将在300名患者中获得， 他们向急诊室（ER）介绍了一个主要的城市教学 在以色列发生一起严重的心理创伤事件后， 在接下来的四个月里，每隔一段时间。 HPA措施 将包括a.）皮质醇、促肾上腺皮质激素（ACTH）和淋巴细胞 在唾液、血液和/或血液中测量的糖皮质激素受体（GR）水平 尿; B.）唾液皮质醇峰-谷差， 曲线和昼夜循环中的下降速率;以及c.）百分比 皮质醇和GR抑制诱导的0.5毫克剂量的合成 类固醇地塞米松。 SNS措施将包括：a.）心率和 血压;和B.）去甲肾上腺素肾上腺素和3-甲氧基-4- 在唾液、血液和/或血液中测量的羟基苯乙二醇（MHPG）水平 尿 Logistic回归将用于预测PTSD与非PTSD状态， 四个月 预测变量将逐步输入到 按时间顺序进行分析，例如，i.）既往创伤史; ii.） 创伤事件严重程度指数，iii.）对指数的反应强度 创伤事件; iv.）ER HPA和SNS措施及其相互作用; 和五）ER后HPA和SNS测量及其相互作用。 在这 的方式，HPA和SNS预测效果和相互作用的评价将 根据其他相关的、先行变量的影响进行调整， 早期HPA轴和SNS的影响和相互作用。

The major objectives of this competing continuation proposal are: a.)to obtain for the first time sequential measures of hypothalamic-pituitary- adrenal (HPA) axis and sympathetic nervous system (SNS) activity in a large sample of psychologically traumatized persons in the immediate aftermath of the traumatic event and in follow-up; b.) to evaluate the time course of HPA and SNS response patterns in relationship to the development of post-traumatic stress disorder (PTSD); and c.) to examine possible interactions between the SNS and HPA axis in PTSD s pathogenesis. HPA and SNS measures will be obtained in 300 patients shortly after their presentation to the emergency room (ER) of a major urban teaching hospital in Israel following an acute, psychologically traumatic event, and at specified intervals during the next four months. HPA measures will include a.) cortisol, adrenocorticotropin (ACTH), and lymphocyte glucocorticoid receptor (GR) levels measured in saliva, blood, and/or urine; b.) salivary cortisol peak-trough difference, area under the curve, and rate of decline over the diurnal cycle; and c.) percentage of cortisol and GR suppression induced by a 0.5 mg dose of the synthetic steroid dexamethasone. SNS measures will include: a.) heart rate and blood pressure; and b.) norepinephrine, epinephrine, and 3-methoxy-4- hydroxy-phenylglycol (MHPG) levels measured in saliva, blood, and/or urine. Logistic regression will be used to predict PTSD vs. non-PTSD status at four months. Predictor variables will be entered stepwise into the analysis on a chronological basis, e.g., i.) past trauma history; ii.) index traumatic event severity, iii.) response intensity to the index traumatic event; iv.) ER HPA and SNS measures and their interactions; and v.) post-ER HPA and SNS measures and their interactions. In this way, evaluation of HPA and SNS predictor effects and interactions will be adjusted for the effects of other relevant, antecedent variables, and for earlier HPA axis and SNS effects and interactions.