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: 8670533
• 负责人: Arieh Y Shalev
• 金额: $ 59.32万
• 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/8670533
• 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; Event; Failure; Functional Magnetic Resonance Imaging; General Hospitals; Grouping; 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; Regulation; Research Personnel; Resolution; Rest; Severities; Staging; Statistical Models; Stress; Structure; Survivors; Symptoms; Testing; Thick; Time; Trauma; Work; base; brain behavior; design; emotion regulation; experience; functional disability; gray matter; high risk; imaging modality; neurobehavioral; neuroimaging; neuromechanism; prevent; prospective; public health relevance; relating to nervous system; resilience; response; segregation; stress resilience; 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）：为了令人信服地揭示新出现的创伤后应激障碍（PTSD）的神经生物学，我们提出了一项方便的、基于功能性MRI的、为期14个月的纵向研究，研究PTSD症状轨迹以及近期创伤幸存者的脑结构和功能改变。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、持续性、伴随的功能障碍以及与其他精神和身体疾病的高共病性，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，包括未缓解、快速缓解和延迟、不完全缓解。这些轨迹提供了PTSD如何发展或缓解的可观察维度，但对PTSD和恢复力的潜在神经生物学的更好理解只能通过将新出现的症状与相关脑回路中的相关动力学联系起来来实现。然而，迄今为止，在大型基于成像的研究中尚未记录演变的PTSD的神经行为相关性，从而留下了重大的知识空白。利用研究者在早期PTSD、高级功能性神经影像学和PTSD神经生物学的成功前瞻性研究中的经验，我们将前瞻性地评估创伤暴露后一年内脑回路中创伤出现的症状和共同发生的动力学。我们将使用功能磁共振成像捕获的反应，参与威胁检测/反应和情绪调节，一个，四个月和十四个月的创伤事件后，在240名幸存者在高风险的创伤后应激障碍从综合医院急诊室招募的脑回路的功能探针。我们将同时评估PTSD、抑郁、焦虑症状和先前与PTSD相关的记忆功能，沿着大脑对上述功能探针的激活模式、功能和结构连接以及结构（体积）特征。因此，我们的目标是（1）使用先进的统计建模方法揭示PTSD症状进展的潜在轨迹（2）识别这些轨迹的神经机制，以及（3）使用高分辨率结构MRI和扩散张量成像识别与PTSD症状轨迹相关的脑结构改变。这项工作中获得的知识将填补一个关键的空白，在理解创伤后应激障碍的发病机制和其时序演变。它还将确定潜在的可修改的神经认知介质的症状轨迹，对构思和设计过程有针对性的，特定阶段的干预措施，并提供急需的信息，从创伤性应激反应早期恢复。这项工作的大范围将产生足够的力量来检测大脑/行为的相关性。