Neurobehavioral Moderators of Post-traumatic Disease Trajectories

创伤后疾病轨迹的神经行为调节因素

• 批准号: 8846673
• 负责人: Arieh Y Shalev
• 金额: $ 55.2万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-07 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8846673
• 关键词: Accident and Emergency department; Acute Post Traumatic Stress Disorder; Anniversary; Anxiety; Attention; Base of the Brain; Behavioral; Biological; Brain; Brain imaging; Characteristics; Chronic; Chronic Disease; Cognitive; Comorbidity; Detection; Diffusion Magnetic Resonance Imaging; Dimensions; Disease; Disease remission; Emotional; Failure; Functional Magnetic Resonance Imaging; General Hospitals; Grouping; Health; High Prevalence; Hippocampus (Brain); Image; Impairment; Intervention; Knowledge; Lateral; Left; Link; Longitudinal Studies; Magnetic Resonance Imaging; Maps; Measures; Mediating; Mediator of activation protein; Memory; Mental Depression; Mental disorders; Methods; Neurobiology; Pathogenesis; Pattern; Phenotype; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Prospective Studies; Psyche structure; Public Health; Recovery; Recruitment Activity; Research Personnel; Resolution; Rest; Severities; Staging; Statistical Models; Stress; Structural defect; Structure; Survivors; Symptoms; Testing; Thick; Time; Trauma; Work; anxiety symptoms; base; brain behavior; brain circuitry; depressive symptoms; design; emotion regulation; experience; functional disability; gray matter; high risk; imaging modality; neurobehavioral; neuroimaging; neuromechanism; prevent; prospective; relating to nervous system; resilience; response; segregation; stress resilience; traumatic event; white matter

DESCRIPTION (provided by applicant): To cogently uncover the neurobiology of emerging post-traumatic stress disorder (PTSD), we propose a conveniently powered, fMRI-based, 14 months long, longitudinal study of PTSD symptom trajectories and concurrent structural and functional brain alterations in recent trauma survivors. PTSD is a severe and often chronic psychiatric disorder that has profound public health impact by virtue of its high prevalence, persistence, accompanying functional impairment and high comorbidity with other mental, and physical disorders. Longitudinal studies of recent trauma survivors describe typical symptom trajectories including non-remission, rapid remission, and delayed, incomplete, remission. These trajectories provide an observable dimension of how PTSD develops, or remits, but a better understanding of underlying neurobiology of both PTSD and resilience can only result from linking emerging symptoms with pertinent dynamics in relevant brain circuits To date, however, the neurobehavioral correlates of evolving PTSD have not been documented in large imaging- based studies, leaving a major knowledge gap. Using the investigators combined experience in successful prospective studies of early PTSD, advanced functional neuroimaging and PTSD neurobiology we will prospectively evaluate trauma-emerging symptoms and co-occurring dynamics in brain circuitry during the year that follows trauma exposure. We will use fMRI captured response to functional probes of brain circuits involved in threat detection/reactivity and emotional regulation, one-, four- and fourteen months after a traumatic event in 240 survivors at high risk for PTSD recruited from a general hospital emergency room. We will simultaneously evaluate PTSD, depression, anxiety symptoms and memory functions previously linked with PTSD, along with brain's activation patterns to the above-mentioned functional probes, functional and structural connectivity and structural (volumetric) characteristics. We thereby aim to (1) uncover latent trajectories of PTSD symptoms progression using advanced statistical modeling methods (2) identify neural mechanisms that underlay these trajectories, and (3) identify structural brain alterations associated with PTSD symptom trajectories using high resolution structural MRI and Diffusion Tensor Imaging. Knowledge gained in this work will fill a critical gap in understanding of the pathogenesis of PTSD and its time-sequenced evolvement. It will also identify potentially modifiable neuro-cognitive mediators of symptom trajectories, towards conceiving and designing processes-targeted, stage-specific interventions, and provide critically needed information on early recovery from traumatic stress. The large scope of this work will yield enough power for detecting brain/behavior correlates.

描述（由申请人提供）：为了更好地揭示新出现的创伤后应激障碍（PTSD）的神经生物学，我们提出了一项便利的、基于功能磁共振成像（fmri）的、长达14个月的创伤后应激障碍症状轨迹和近期创伤幸存者同时发生的大脑结构和功能改变的纵向研究。创伤后应激障碍是一种严重的慢性精神疾病，由于其高患病率、持久性、伴随的功能损伤以及与其他精神和身体疾病的高合并症，对公共卫生产生了深远的影响。近期创伤幸存者的纵向研究描述了典型的症状轨迹，包括非缓解、快速缓解和延迟、不完全缓解。这些轨迹提供了创伤后应激障碍如何发展或缓解的可观察维度，但要更好地理解创伤后应激障碍和恢复力的潜在神经生物学，只能将新出现的症状与相关脑回路中的相关动力学联系起来。然而，迄今为止，创伤后应激障碍演变的神经行为相关性尚未在大型影像学研究中得到记录，留下了一个主要的知识空白。利用研究人员在早期创伤后应激障碍、先进功能神经影像学和创伤后应激障碍神经生物学的成功前瞻性研究的经验，我们将前瞻性地评估创伤暴露后一年内出现的创伤症状和脑回路中共同发生的动力学。我们将在创伤事件发生1个月、4个月和14个月后，从综合医院急诊室招募240名创伤后应激障碍高风险幸存者，使用功能磁共振成像捕捉到涉及威胁检测/反应性和情绪调节的脑回路功能探针的反应。我们将同时评估创伤后应激障碍、抑郁、焦虑症状和先前与创伤后应激障碍相关的记忆功能，以及上述功能探针的大脑激活模式、功能和结构连接以及结构（体积）特征。因此，我们的目标是：(1)利用先进的统计建模方法揭示PTSD症状进展的潜在轨迹；(2)确定这些轨迹背后的神经机制；(3)利用高分辨率结构MRI和弥散张量成像识别与PTSD症状轨迹相关的大脑结构改变。在这项工作中获得的知识将填补理解创伤后应激障碍发病机制及其时间序列演变的关键空白。它还将确定症状轨迹的潜在可改变的神经认知介质，以构思和设计针对过程的特定阶段的干预措施，并提供创伤应激早期恢复的急需信息。这项工作的大范围将产生足够的能量来检测大脑/行为的相关性。