Neurophysiology Markers of PTSD's Presence, Severity, and Therapy Outcome

创伤后应激障碍（PTSD）是一种慢性和致残性焦虑症，由暴露于 创伤性事件，与行为以及社会和职业功能的显著缺陷有关。 美国（US）退伍军人患创伤后应激障碍的风险很高， 越南退伍军人估计为19%，而在OEF/OIF士兵和退伍军人中，大约17%的人 伊拉克战争中的现役士兵和25%的预备役士兵符合PTSD的标准。 目前诊断和管理PTSD的实践主要依赖于主观临床评估， 临床医生和患者自我报告。一种独立、客观和基于神经生理学的方法， 直接评估大脑功能是不可用的，但非常需要改善诊断和管理， 创伤后应激障碍国家科学院医学研究所的建议强调了这一需要 （IOM-NAS），对当前PTSD诊断和治疗进行了全面评估 方法，并确定了目前的诊断和治疗技术的潜在缺点。一个主要 IOM-NAS的建议是迫切需要开发更精确和更有效的方法。 客观诊断创伤后应激障碍及其严重程度，客观和快速评估治疗效果，以及 能够预测谁可能有复发的风险。 为了解决迫切需要发展客观的方法来诊断创伤后应激障碍，确定其严重程度， 水平，并可能预测治疗反应，我们建议测试新的生物标志物，这是基于 测量睡眠期间大脑皮层区域之间的连贯活动。本次测试的选择 条件（睡眠）的动机是睡眠障碍的个人非常高的患病率， 创伤后应激障碍，以至于有些人假设睡眠障碍是这种疾病的标志性特征。在 对单独患有PTSD的退伍军人（n=38），单独患有TBI的退伍军人（n=30）， PTSD和TBI组（n=25）和无PTSD或TBI对照组（n=38），我们已经证明，一组神经标志物 对PTSD的存在高度敏感/特异，对症状的严重程度高度敏感， PTSD组。本Merit项目的总体目标是在以下方面验证这种新型神经生理学标志物：（1） 回顾性研究，分析将应用于现有的大型健康相关数据库（n=656） 生活质量和功能结果的措施，以及睡眠脑电图记录，从退伍军人与创伤后应激障碍 仅患有TBI，患有PTSD和TBI，仅患有抑郁症（无PTSD或TBI），以及对照组（无PTSD， TBI、抑郁症、睡眠呼吸暂停），（2）PTSD（n=10）和对照组（n=10）的前瞻性研究1，我们将 使用密集阵列（64通道）评价神经标志物性能的潜在改善 EEG蒙太奇，和（3）前瞻性研究2，在接受心理治疗的退伍军人队列（n=50）中，其中 我们将评估神经标志物对PTSD症状改善的敏感性，以及其他功能性指标， 和健康相关的生活质量的措施，在响应心理治疗。

Post-traumatic stress disorder (PTSD), a chronic and disabling anxiety disorder that results from exposure to a traumatic event, is associated with marked deficits in behavioral as well as social and occupational functioning. United States (U.S.) military Veterans’ risk of developing PTSD is high, lifetime prevalence of PTSD among Vietnam Veterans is estimated at 19%, while among OEF/OIF soldiers and Veterans, approximately 17% of active duty soldiers and 25% of reserve soldiers from the Iraq war met criteria for PTSD. Current practice for diagnosing and managing PTSD relies primarily on subjective clinical assessments by clinicians as well as patient self-report. An independent, objective and neuro-physiology based method for directly assessing brain function is not available, but is much needed to improve diagnosis and management of PTSD. This need is highlighted by recommendations from the Institute of Medicine, National Academy of Science (IOM-NAS), which conducted a comprehensive assessment of the current PTSD diagnosis and treatment methods and identified potential shortcomings of current diagnostic and treatment techniques. A major recommendation by the IOM-NAS was the urgent need for development of methods for more precise and objective diagnosis of PTSD and its severity level, objective and faster evaluation of treatment efficacy, and ability to predict who might be at risk of relapse. To address the critical need for developing objective methods for diagnosis of PTSD, determining its severity level, and potentially predicting treatment response, we propose to test novel biomarkers which are based on measures of coherent activity among the regions of cerebral cortex during sleep. The selection of this test condition (sleep) was motivated by the extraordinarily high prevalence of sleep disturbances in individuals with PTSD, so much so that some have postulated that sleep disturbances are a hallmark feature of the disorder. In preliminary studies on EEG acquired during sleep from Veterans with PTSD alone (n=38), TBI alone (n=30), PTSD and TBI (n=25), and no PTSD or TBI control group (n=38), we have shown that a set of neuromarkers were highly sensitive/specific to the presence of PTSD, and highly sensitive to the severity of symptoms in PTSD group. The overall goal of this Merit project is to validate this novel neurophysiology marker in: (1) retrospective study, where the analyses will be applied to a large existing database (n=656) of health-related quality of life and functional outcome measures, as well as sleep EEG recordings, from Veterans with PTSD only, with TBI only, with both PTSD and TBI, with depression only ( no PTSD or TBI), and controls (no PTSD, TBI, Depression, Sleep Apnea), (2) prospective study 1 with PTSD (n=10) and control (n=10) where we will evaluate potential improvement on the performance of the neuromarkers using a dense array (64 channel) EEG montage , and (3) prospective study 2 in a cohort (n=50) of Veterans undergoing psychotherapy, where we will evaluate the sensitivity of neuromarkers to the improvements in PTSD symptoms, and other functional and health related quality of life measures, in response to psychotherapy.