STRESS-INDUCED STARTLE MODULATION IN PTSD

本提案的目的是阐明 夸张的惊吓反应是波斯特的标志之一 创伤性应激障碍（PTSD）。 不可避免的休克的动物研究 和心理生理学的调查， 创伤后应激障碍表明，条件和非条件机制必须 创伤后应激障碍的发病机制。 概念框架 所提出的研究是基于动物模型的条件和 无条件压力引起的惊吓调节，即恐惧， 加强惊吓，惊吓的休克敏化，和应激诱导的 前脉冲抑制的丧失。 PTSD退伍军人的高反应性也可能 指出了在处理环境刺激方面的普遍缺陷。 我们 发现创伤后应激障碍的退伍军人过度关注 外部刺激。 我们将试图进一步描述这种赤字 事件相关电位（ERP）。 我们亦会进行研究， 用脑干听觉诱发电位（BAEP）探测感觉神经元， 处理. 任何信息缺陷 处理和异常惊吓调制也将被检查。 惊吓调制和处理外部刺激将是 在基线和实验诱导应激期间进行研究 在患有PTSD的退伍军人（N=44）和适当的平民（N=82）中， 退伍军人（N=81）对照组。 应力条件将包括 对电击的预期和对创伤场景的观看。 强烈的电击引起的惊吓反射的眨眼成分 将测量突然开始的声刺激 肌电图检查。 对外界刺激的认知处理 用由各种类型的刺激引起的ERP进行研究， 是为了吸引目标的注意力 BAEP将在 仅在基线测量。 拟议研究的结果将澄清是否增加了 PTSD患者对感觉刺激的反应反映了一种慢性升高的 唤醒或刺激诱导的状态。 这些实验可以提供一个 为更客观的诊断方法和更好的 通过核心特征评估治疗结果 PTSD的症状 此外，我们目前的知识水平， 压力相关惊吓的神经生物学基础的描述 在动物中的调制可以导致识别的模式， 大脑失调与创伤后应激障碍有关，并可能最终导致 开发更好的行为和药物治疗 治疗这种疾病的方法

The aim of this proposal is to elucidate the mechanisms underlying the exaggerated startle response which is one of the hallmarks of Post Traumatic Stress Disorder (PTSD). Animal studies of inescapable shock and psychophysiological investigations in Vietnam war veterans with PTSD suggest that both conditioned and unconditioned mechanisms must be considered in the pathogenesis of PTSD. The conceptual framework for the proposed study is based on animal models of conditioned and unconditioned stress-induced startle modulation, namely, fear- potentiated startle, shock sensitization of startle, and stress-induced loss of prepulse inhibition. Hyperreactivity of PTSD veterans may also point to a general deficit in processing environmental stimuli. We have found that PTSD veterans engaged excessive attention toward external stimuli. We will attempt to further characterize this deficit using event-related potentials (ERP). We will also conduct a study using brainstem auditory evoked potentials (BAEP) to explore sensory processing. The relationship between any impairments in information processing and abnormal startle modulation will also be examined. Startle modulation and processing of external stimuli will be investigated both at baseline and during experimentally-induced stress in veterans with PTSD (N=44) and appropriate civilian (N=82) and veteran (N=81) control subjects. The stress conditions will consist of anticipation of electric shocks and the viewing of traumatic scenes. The eyeblink component of the startle reflex elicited by an intense acoustic stimulus with abrupt onset will be measured electromyographically. Cognitive processing of external stimuli will be investigated with ERPs elicited by various types of stimuli that are designed to attract the subject's attention. The BAEPs will be measured at baseline only. The results of the proposed study will clarify whether the increased reactivity to sensory stimulation in PTSD reflects a chronic elevated arousal or a stimulus-induced state. These experiments may provide a foundation for more objective diagnostic approaches and a better assessment of treatment outcome through the characterization of core symptoms of PTSD. In addition, our current state of knowledge from the delineation of the neurobiological substrates of stress-related startle modulation in animals could lead to the identification of patterns of brain dysregulation involved in PTSD and could ultimately result in the development of better behavioral and pharmacological treatment approaches for this disorder.