Study of early brain alterations that predict development of chronic PTSD

预测慢性创伤后应激障碍（PTSD）发展的早期大脑改变的研究

• 批准号: 9405530
• 负责人: Xin Wang
• 金额: $ 68万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-23 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9405530
• 关键词: Accident and Emergency department; Acute Pain; American; Amygdaloid structure; Anterior; Attention; Base of the Brain; Brain; Brain region; Characteristics; Chronic; Chronic Post Traumatic Stress Disorder; Development; Diagnosis; Early identification; Economic Burden; Emotional; Emotions; Evaluation; Fright; Functional Magnetic Resonance Imaging; Grant; High Prevalence; Hippocampus (Brain); Intervention; Lead; Left; Longitudinal Studies; Machine Learning; Magnetic Resonance Imaging; Measures; Medial; Memory; Monitor; National Institute of Mental Health; Outcome; Patients; Pattern; Post-Traumatic Stress Disorders; Prefrontal Cortex; Prevention; Process; Public Health; Recovery; Recruitment Activity; Regulation; Reporting; Research; Severities; Stress Tests; Structure; Survivors; Symptoms; Testing; Thick; Time; Trauma; Traumatic Brain Injury; Work; acute stress; associated symptom; base; brain volume; cingulate cortex; cohort; conditioned fear; density; emotion regulation; exhaustion; gray matter; high risk; insight; neuroimaging; pain symptom; prevent; prospective; response; socioeconomics; stress symptom; trauma symptom; traumatic event

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.

数百万美国人在创伤事件中幸存下来 (1)。第一年的症状轨迹 创伤后可能导致慢性创伤后应激障碍 (PTSD) 或 康复后无创伤后应激障碍 (PTSD) (2-16)。神经影像学研究表明慢性 PTSD 症状与 大脑功能和结构发生变化 (17-32)；因此，早期的认识 创伤后大脑变化提供了预测慢性创伤后应激障碍 (PTSD) 的机会 (33-35)。鉴别 创伤后症状进展背后的大脑变化也将提供洞察力 区分 PTSD 发展和 PTSD 自由恢复的机制 (27, 36-38)。出奇， 很少有人对创伤幸存者的创伤后早期进行性大脑变化进行研究。 随后发展为创伤后应激障碍 (PTSD) (33, 34)。 PI R21 资助的最新结果表明： 随后被诊断的创伤幸存者的早期和进行性大脑差异 与非 PTSD 幸存者相比，3 个月时患有 PTSD 的幸存者。这些差异包括较小的体积 左海马 (HC) 和吻侧前扣带皮层 (rACC) 以及大前额叶皮层 (PFC) 在创伤后 10 天内激活功能磁共振成像情绪评估任务。此外，在 3 个月时出现 PTSD 的幸存者，PFC 结构和恐惧评估逐渐下降 在 3 个月内发现岛叶皮层 (IC) 的情绪反应被激活并增加。 基于这些发现，我们提出了关于早期和渐进情绪回路的工作假设 导致 PTSD 发展的变化。为了检验这个假设，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，这些变化有助于并且可以 用于预测慢性 PTSD。 对急诊科 (ED) 招募的创伤幸存者将进行纵向研究，从 创伤后 2 周内至 1 年内。功能性 MRI (fMRI) 激活与 将研究 PTSD 和非 PTSD 创伤中负面情绪的处理、记忆和调节 幸存者使用注意力转移情绪评估（SEAT）和恐惧调节（FCT）任务。 结构性 MRI (sMRI) 将检查大脑情绪回路的结构。早期大脑功能和 一年后发生和未发生 PTSD 的幸存者的结构差异和症状 将使用机器学习方法来识别和分析创伤，以预测 PTSD 与 非 PTSD 结果。 PTSD 和非 PTSD 患者大脑功能和结构随时间的差异 幸存者将被识别，这些差异和进展之间的关联 将检查症状。拟议的工作填补了当前理解的一个重要空白 识别导致 PTSD 发展的早期和进行性大脑变化。我们的方法 可用于识别基于大脑的 PTSD 发展标记，并识别创伤幸存者 慢性创伤后应激障碍（PTSD）的高风险。