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）。最初一年的症状轨迹 可能导致慢性创伤后应激障碍（PTSD）的发展， 无创伤后应激障碍（2-16）。神经影像学研究表明慢性创伤后应激障碍症状 随着大脑功能和结构的变化（17-32）;因此， 创伤后大脑变化为预测慢性PTSD提供了机会（33-35）。识别 创伤后症状进展背后的大脑变化也将提供对 机制，区分创伤后应激障碍的发展从创伤后应激障碍免费恢复（27，36- 38）。令人惊奇的是， 创伤后早期进行性脑变化很少在创伤幸存者中进行研究， 随后发展PTSD（33，34）。PI的R21赠款的最新结果提供了以下迹象： 创伤幸存者早期和进行性脑差异， 与非创伤后应激障碍幸存者相比，3个月时患有创伤后应激障碍。这些差异包括体积较小 左侧海马（HC）和喙前扣带皮层（rACC）和大前额叶皮层 (PFC)在创伤后10天内激活fMRI情绪评估任务。更以 在3个月时发展为PTSD的幸存者，PFC结构和恐惧评估进行性下降 在3个月内发现岛叶皮层（IC）中的情绪反应的激活和增加。 基于这些发现，我们提出了一个关于早期和渐进式情绪回路的工作假说 导致创伤后应激障碍发展的变化。为了验证这一假设，我们建议使用一组 创伤幸存者，以确定早期和渐进的大脑变化，有助于， 可以用来预测慢性创伤后应激障碍 在急诊科招募的创伤幸存者将进行纵向研究，从 创伤后2周至1年。功能性磁共振成像（fMRI）激活与 将在创伤后应激障碍和非创伤后应激障碍创伤中研究负面情绪的处理、记忆和调节 幸存者使用转移注意情绪评估（SEAT）和恐惧条件反射（FCT）任务。 结构MRI（sMRI）将检查大脑情感回路的结构。早期脑功能和 创伤后应激障碍幸存者与未患创伤后应激障碍幸存者在1年后的结构差异和症状 将使用机器学习方法识别和分析创伤，以预测PTSD与 非PTSD的结果。PTSD和非PTSD患者大脑功能和结构随时间的差异 幸存者将被确定，这些差异和进展之间的关联， 将检查症状。拟议的工作填补了目前认识上的一个重要空白， 识别导致PTSD发展的早期和渐进性大脑变化。我们的方法 可以用于识别PTSD发展的脑标记物，并识别创伤幸存者， 患慢性创伤后应激障碍的风险很高