Study of early brain alterations that predict development of chronic PTSD

数百万美国人在创伤性事件中幸存下来(1)。最初一年的症状轨迹 创伤后可导致慢性创伤后应激障碍(PTSD)或 没有创伤后应激障碍的康复(2-16)。神经成像研究表明慢性创伤后应激障碍症状与 随着大脑功能和结构的变化(17-32)；因此，早期的识别 创伤后脑变化为预测慢性创伤后应激障碍(33-35岁)提供了机会。鉴定 作为创伤后症状进展的基础的大脑变化也将提供对 区分创伤后应激障碍发展与无创伤后应激障碍恢复的机制(27，36-38)。令人惊讶的是， 很少有人研究创伤幸存者在创伤后早期的进行性脑变化 随后发展为创伤后应激障碍(33，34)。PI R21赠款的最新结果提供了以下迹象 随后被诊断为创伤幸存者的早期和进展性脑差异 与非创伤后应激障碍幸存者相比，3个月后患有创伤后应激障碍的患者。这些区别包括较小的体积 左侧海马区(Hc)、吻侧前扣带回(RACC)和大前额叶皮质 (PFC)在创伤后10天内对功能磁共振情绪评估任务进行激活。此外，在 在3个月时出现创伤后应激障碍的幸存者，PFC结构和恐惧评估的进行性下降 在3个月内，岛叶皮质(IC)的情绪反应被激活和增加。 基于这些发现，我们提出了一个关于早期和进行性情绪回路的工作假说 导致创伤后应激障碍发展的变化。为了检验这一假设，我们建议使用一组 创伤幸存者识别早期和进行性的大脑变化，这些变化有助于并可以 用于预测慢性创伤后应激障碍。 将对急诊科招募的创伤幸存者进行纵向研究，从 创伤后2周内，最长1年。功能磁共振成像(FMRI)激活与 将研究创伤后应激障碍和非创伤后应激障碍患者的负性情绪的处理、记忆和调节 幸存者使用转移注意力情绪评估(SEAT)和恐惧条件反射(FCT)任务。 结构磁共振成像(SMRI)将检查大脑情绪回路中的结构。早期的脑功能和 1年后发生创伤后应激障碍与未发生创伤后应激障碍的幸存者的结构差异和症状 将使用机器学习方法识别和分析创伤，以预测创伤后应激障碍与 非创伤后应激障碍的结果。创伤后应激障碍与非创伤后应激障碍患者脑功能和结构随时间的差异 幸存者将被确认，这些差异和进展之间的联系 将对症状进行检查。拟议的工作填补了当前理解中的一个重要空白， 识别有助于创伤后应激障碍发展的早期和渐进性大脑变化。我们的方法 可用于确定创伤后应激障碍发展的基于大脑的标志物，并在 患慢性创伤后应激障碍的风险很高。

Millions of Americans survive traumatic events (1). Symptom trajectories over the initial year after trauma can lead to development of chronic post-traumatic stress disorder (PTSD) or to a recovery free of PTSD (2-16). Neuroimaging studies indicate chronic PTSD symptoms are associated with changes in brain function and structure (17-32); consequently, recognition of early post-trauma brain changes provides an opportunity to predict chronic PTSD (33-35). Identification of brain changes that underlie post-trauma symptom progressions will also provide insight into mechanisms that distinguish PTSD development from PTSD free recovery (27, 36- 38). Surprisingly, progressive brain changes early after trauma have rarely been studied in trauma survivors who subsequently develop PTSD (33, 34). Recent results from the PI’s R21 grant provide indications of both early and progressive brain differences in trauma survivors who were subsequently diagnosed with PTSD at 3 months as compared to non-PTSD survivors. These differences include smaller volumes of left hippocampus (HC) and rostral anterior cingulate cortex (rACC) and greater prefrontal cortex (PFC) activation to an fMRI emotion appraisal task within 10 days after trauma. Furthermore, in survivors who developed PTSD at 3 months, progressive decreases in PFC structure and fear appraisal activation and increases in emotional responses in insular cortex (IC) were found over 3 months. Based on these findings we developed a working hypothesis on early and progressive emotion circuit changes that lead to PTSD development. To test this hypothesis, we propose to use a cohort of trauma survivors to identify early and progressive brain changes that contribute to, and that can be used to predict, chronic PTSD. Trauma survivors recruited in Emergency Departments (EDs) will be longitudinally studied, starting within 2 weeks and out to 1 year after trauma. Functional MRI (fMRI) activation associated with processing, memory, and regulation of negative emotions will be studied in PTSD and non-PTSD trauma survivors using Shifted- attention Emotion Appraisal (SEAT) and Fear Conditioning (FCT) tasks. Structural MRI (sMRI) will examine structures in brain emotion circuits. Early brain functional and structural differences and symptoms in survivors who do versus do not develop PTSD at 1 year after trauma will be identified and analyzed using machine learning approaches to predict PTSD versus non-PTSD outcomes. Differences over time in brain function and structure in PTSD and non-PTSD survivors will be identified, and associations between these differences and progressions of symptoms will be examined. The proposed work fills an important gap in current understanding by identifying early and progressive brain changes that contribute to PTSD development. Our approach can serve to identify brain-based markers for PTSD development and to identify trauma survivors at high risk for chronic PTSD.