Neuroimaging correlates of impaired fear inhibition in PTSD

神经影像学与 PTSD 恐惧抑制受损的相关性

基本信息

批准号：
8445796
负责人：
Tanja Jovanovic
金额：
$ 23.19万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-19 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8445796
关键词：
Active Learning Advocate Affect African American Amygdaloid structure Anterior Anxiety Area Arousal Basic Science Biological Brain Clinical Cognitive Complex Coupled Cues DSM-IV Data Development Diagnosis Diagnostic and Statistical Manual Dimensions Disease Environment Event Exhibits Exposure to Extinction (Psychology)Family Fright Functional Magnetic Resonance Imaging Functional disorder Genes Goals Hippocampus (Brain)Image Imaging Device Imaging Techniques Incidence Individual Individual Differences Insula of Reil Investigation Laboratories Learning Limbic System Link Low income MRI Scans Measurement Measures Medical Mental Depression Mental disorders Methods Neurobiology Neurosciences Research Patients Phenotype Physiological Plant Roots Population Post-Traumatic Stress Disorders Prefrontal Cortex Prevalence Prevention program Psychopathology Research Resolution Risk Risk Factors Safety Severities Shapes Signal Transduction Structure Substance abuse problem Surface Symptoms Testing Trauma United States National Institutes of Health Variant Violence War base cingulate cortex combat conditioning dentate gyrus experience high risk improved innovation insight interest intervention program men neurobiological mechanism neuroimaging novel relating to nervous system resilience response tool

项目摘要

DESCRIPTION (provided by applicant): Posttraumatic stress disorder (PTSD) occurs in some people after exposure to events that cause extreme fear or helplessness. The incidence of war zones worldwide and the prevalence of violence in large urban centers in the U.S., increases the likelihood of exposure to traumatizing events. Of those who survive such events, approximately 10% will develop this debilitating disorder that affects both the individual and thei family. Individual patients can vary in the degree to which they present with the different symptom clusters, such that a "one size fits all" treatment is often inadequate. This individual variation may be associated with biological risk factors that increase vulnerability to the disorde or impede treatment. While both genes and environment interact to increase an individual's risk of developing PTSD, it is unclear how the underlying neurobiology is shaped by these factors to result in the observed dysregulations. PTSD is marked by impaired cortical control of the limbic system, specifically the amygdala and hippocampus. We have found that one of the hallmark physiological markers associated with PTSD symptom severity is the inability to inhibit the fear response under safe conditions. This phenotype appears to be a robust marker regardless of trauma type, as it is observed in both civilian and combat PTSD populations. The proposed study will capitalize on this observable marker and individual variability among traumatized individuals to investigate the structural and functional neural underpinnings of impaired fear inhibition. By comparing analyses of this physiological phenotype to the DSM defined disorder, the study will use an innovative approach to understand the pathophysiology of PTSD. The use of state-of-the art imaging tools to fine- tune the measurements of size, shape, and function of the brain areas involved in fear inhibition will offer much-needed insight into individual differences in vulnerability to trauma. PUBLIC HEALTH RELEVANCE: Posttraumatic stress disorder (PTSD) is a highly debilitating and complex disorder frequently co-morbid with many medical and psychiatric illnesses. Understanding the neurobiological mechanisms underlying this disorder will provide improved tools for targeting symptoms that are specific to PTSD. The ultimate goal of this application is to combine clinical psychopathology research and basic neuroscience research to inform the development of novel and effective approaches for treating PTSD, particularly in high-risk populations such as low-income, African-Americans.

描述（由申请人提供）：一些人在经历导致极度恐惧或无助的事件后会出现创伤后应激障碍（PTSD）。世界范围内战区的频繁发生以及美国大城市中心暴力事件的普遍存在，增加了遭受创伤性事件的可能性。在此类事件的幸存者中，大约 10% 的人会患上这种使个人及其家人衰弱的疾病。个体患者表现出不同症状群的程度可能有所不同，因此“一刀切”的治疗通常是不够的。这种个体差异可能与生物风险因素有关，这些因素增加了疾病的脆弱性或阻碍了治疗。虽然基因和环境相互作用会增加个体患 PTSD 的风险，但目前尚不清楚这些因素如何影响潜在的神经生物学，从而导致观察到的失调。 PTSD 的特点是边缘系统的皮质控制受损，特别是杏仁核和海马体。我们发现，与 PTSD 症状严重程度相关的标志性生理标志之一是在安全条件下无法抑制恐惧反应。无论创伤类型如何，这种表型似乎都是一个强有力的标记，正如在平民和战斗创伤后应激障碍人群中观察到的那样。拟议的研究将利用这一可观察到的标记和受创伤个体的个体差异来研究恐惧抑制受损的结构和功能神经基础。通过将这种生理表型的分析与 DSM 定义的疾病进行比较，该研究将使用一种创新方法来了解 PTSD 的病理生理学。使用最先进的成像工具来微调参与恐惧抑制的大脑区域的大小、形状和功能的测量，将为了解创伤脆弱性的个体差异提供急需的见解。公共卫生相关性：创伤后应激障碍 (PTSD) 是一种使人高度衰弱的复杂疾病，经常与许多医学和精神疾病同时发病。了解这种疾病背后的神经生物学机制将为针对 PTSD 特有症状提供改进的工具。该应用程序的最终目标是将临床精神病理学研究和基础神经科学研究结合起来，为治疗创伤后应激障碍（PTSD）的新颖有效方法的开发提供信息，特别是在低收入非裔美国人等高危人群中。