Neurobehavioral Moderators of Post-traumatic Disease Trajectories

描述(申请人提供)：为了有力地揭示新出现的创伤后应激障碍(PTSD)的神经生物学，我们提出了一项基于功能磁共振成像的、为期14个月的、方便的、对最近创伤幸存者的PTSD症状轨迹和同时发生的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、往往是慢性的精神疾病，由于其高患病率、持久性、伴随的功能损害以及与其他精神和身体疾病的高共患性，对公众健康具有深远的影响。对近期创伤幸存者的纵向研究描述了典型的症状轨迹，包括无缓解、快速缓解和延迟、不完全缓解。这些轨迹为创伤后应激障碍的发展或缓解提供了一个可观察的维度，但更好地理解创伤后应激障碍和复原力的潜在神经生物学只能通过将新出现的症状与相关大脑回路中的相关动力学联系起来才能产生，然而，到目前为止，演变中的创伤后应激障碍的神经行为相关性尚未在基于成像的大型研究中被记录下来，这留下了一个重大的知识空白。利用研究人员结合早期创伤后应激障碍、先进的功能神经成像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创伤新出现的症状和大脑回路中的共生动力学。我们将使用fMRI捕捉到的对参与威胁检测/反应和情绪调节的大脑回路的功能探针的反应，在创伤事件发生后1、4和14个月从综合医院急诊室招募的240名创伤后应激障碍高危幸存者。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，以及大脑对上述功能探针的激活模式、功能和结构连通性以及结构(体积)特征。因此，我们的目标是(1)使用先进的统计建模方法来发现PTSD症状进展的潜在轨迹，(2)识别这些轨迹背后的神经机制，以及(3)使用高分辨率结构磁共振和扩散张量成像来识别与PTSD症状轨迹相关的结构性脑改变。在这项工作中获得的知识将填补在理解创伤后应激障碍的发病机制及其时间顺序演变方面的一个关键空白。它还将确定症状轨迹的潜在可修改神经认知介体，以构思和设计有针对性的、阶段特定的干预过程，并提供有关创伤应激早期恢复的迫切需要的信息。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。

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.