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: 9260326
• 负责人: Xin Wang
• 金额: $ 77.32万
• 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/9260326
• 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; Machine Learning; Magnetic Resonance Imaging; Measures; Medial; 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; 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; meetings; memory process; neuroimaging; pain symptom; prevent; 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.

数以百万计的美国人在创伤事件中幸存下来(1)。最初一年的症状轨迹