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: 10004715
• 负责人: Xin Wang
• 金额: $ 65.87万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10004715
• 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; 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; post-trauma; prevent; prospective; recruit; response; socioeconomics; stress related disorder; stress symptom; trauma exposure; trauma symptom; traumatic event; 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; 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; post-trauma; prevent; prospective; recruit; response; socioeconomics; stress related disorder; stress symptom; trauma exposure; 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.

成千上万的美国人在创伤事件中幸存下来（1）。症状轨迹在第一年 创伤后会导致慢性创伤后应激障碍（PTSD）或 无PTSD的恢复（2-16）。神经影像学研究表明慢性PTSD症状与 随着脑功能和结构的变化（17-32）；因此，认识早期 创伤后大脑的变化提供了预测慢性PTSD的机会（33-35）。鉴别 构成创伤后症状进展的大脑变化也将为您提供洞察力 将PTSD发育与PTSD Free Recovery区分开的机制（27，36-38）。出奇， 创伤后早期的渐进大脑变化很少在创伤表面上研究 随后开发了PTSD（33，34）。 PI的R21赠款的最新结果提供了指示 后来被诊断出的创伤生存期的早期和进行性大脑差异 与非PTSD表面相比，有3个月时的PTSD。这些差异包括较小的卷 左海马（HC）和前扣带回皮层（RACC）和较大的前额叶皮层 （PFC）在创伤后10天内激活fMRI的情感评估任务。此外，在 在3个月时开发PTSD的幸存者，PFC结构的逐步下降和恐惧评估 在3个月内发现了岛状皮质（IC）中情绪反应的激活和情绪反应的增加。 根据这些发现，我们对早期和渐进的情感电路提出了一个工作的假设 导致PTSD开发的变化。为了检验这一假设，我们建议使用 创伤生存以识别促成促成的早期和渐进的大脑变化，这可以 用于预测慢性PTSD。 在急诊部门（ED）招募的创伤表面将是纵向研究的 在创伤后2周内和1年之内。功能性MRI（fMRI）激活 负面情绪的处理，记忆和调节将在PTSD和非PTSD创伤中进行研究 幸存者使用转移的注意力情绪评估（座位）和恐惧条件（FCT）任务。 结构MRI（SMRI）将检查大脑情绪电路中的结构。早期大脑功能和 与之相对于未在1年后不发展PTSD的生存的结构差异和症状 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的大脑功能和结构的随着时间的差异 将确定幸存者，这些差异与进步之间的关联 将检查症状。拟议的工作填补了当前理解的重要差距 确定有助于PTSD发展的早期和渐进的大脑变化。我们的方法 可以用来识别基于大脑的标记，以进行PTSD开发，并确定在 慢性PTSD的高风险。