Acute Neurocognitive-affective Predictors of Chronic Post-trauma Outcomes

 描述（由申请人提供）：创伤暴露是非常常见的，并增加了一系列负面健康结果的风险，最明显的是创伤后应激障碍（PTSD）。鉴于创伤暴露的潜在有害后遗症，确定急性创伤后风险因素预测慢性创伤后应激障碍和其他不良创伤后结局至关重要。虽然这方面的努力取得了一些进展，但事实证明，很难确定最近受过创伤的人是否有长期创伤后调整不良的风险。在这个项目中，我们的目标是确定急性和慢性创伤后症状的预测因子，更重要的是，确定急性创伤后措施，预测慢性创伤后应激障碍，以及其他综合征，包括抑郁症和物质使用问题。我们将评估三个过程的预测效用，这三个过程1）植根于基本的认知和情感神经科学，2）在RDoC矩阵中表达，3）直接映射到既定的干预措施，4）在我们的初步数据中显示出希望。利用我们在威斯康星州医学院1级创伤服务中对大量患者人群的独特访问，我们将对创伤后和其他症状进行多层次（神经回路，生理，行为，自我报告）纵向评估，并基于RDoC预测这些症状。在创伤暴露的两周内，我们将评估基于RDoC的假设增加创伤后应激症状的过程指数，包括条件性恐惧的消退和消退的保持（急性威胁/恐惧，持续威胁），威胁过滤受损（注意力控制），以及对威胁的注意偏向（持续威胁）。在暴露后六个月，我们将再次对这些过程进行多层次评估，并测量PTSD和其他相关综合征的症状。除了这两个主要评估点（均涉及神经影像学）外，我们还将收集暴露后24个月内多个时间点的认知和情感功能以及症状严重程度的成套指标。我们将在2周时扫描220名个体，对急性创伤后症状进行过采样，目标是最终6个月样本为200人，最终24个月样本为150人。我们假设，急性损伤的恐惧消退，灭绝相关的可塑性（改变静息状态的功能 注意力过滤和注意力偏差将在暴露后6至24个月内预防PTSD症状的升高。这项工作提供了几个关键的创新：1）急性创伤患者的纵向多水平评估，2）使用神经测量来预测长期结果，3）使用一种新的范式来评估预防诱导的可塑性，以及4）在同一样本中，灭绝和注意力的结合，这两种核心机制被假设为增加PTSD的风险。我们希望这个项目通过使用基于基础科学的RDoC指数，将其转化为临床指标，并直接与外科确定的干预措施联系起来，进一步推进NIMH的使命。这项工作的发现将提供新的知识，帮助早期识别创伤暴露的个体最有可能患慢性PTSD，并可能成为早期干预的目标。

 DESCRIPTION (provided by applicant): Trauma exposure is extremely common and increases risk for a host of negative health outcomes, most notably posttraumatic stress disorder (PTSD). Given the potential harmful sequelae of trauma exposure, it is crucial to identify acute post-trauma risk factors that predict chronic PTSD and other poor post-trauma outcomes. While some progress has been made in this effort, attempts to identify recently traumatized individuals at risk for poor long-term post-trauma adjustment have proven difficult. In this project we aim to identify predictors of both acute and chronic posttrauma symptoms, and more importantly, identify acute post-trauma measures that predict chronic PTSD, as well as other syndromes including depression and substance use problems. We will assess the predictive utility of three processes that are 1) rooted in basic cognitive and affective neuroscience, 2) articulated in the RDoC matrix, 3) map directly onto established interventions, and 4) show promise in our preliminary data. Leveraging our unique access to the large patient population in the Level 1 trauma service at the Medical College of Wisconsin, we will conduct multi-level (neural circuits, physiology, behavior, self-report) longitudinal assessments of posttrauma and other symptoms, and RDoC-based predictors of these symptoms. Within two weeks of trauma exposure we will assess RDoC-based indices of processes hypothesized to in- crease posttraumatic stress symptoms, including extinction and retention of extinction of conditioned fear (Acute Threat/Fear, Sustained Threat), impaired filtering of threat (Attentional Control), and attentional bias to threat (Sustained Threat). At six months post-exposure we will again conduct multilevel assessments of these processes and measure symptoms of PTSD and other relevant syndromes. In addition to these two primary assessment points (both involving neuroimaging), we will also collect a battery indexing cognitive and affective functioning and symptom severity at multiple points up to 24 months post-exposure. We will scan 220 individuals, oversampled for acute posttrauma symptoms, at 2 weeks with the goal of a final six-month sample of 200, and a final 24-month sample of 150. We hypothesize that acute impairments in fear extinction, extinction- related plasticity (changes in resting state functional connectivity from before to after extinction), attentional filtering, and attentional bias will preict elevated PTSD symptoms six to twenty-four months post-exposure. This work offers several key innovations: 1) longitudinal multi-level assessment of acutely traumatized patients, 2) the use of neural measures to predict long-term outcomes, 3) the use of a novel paradigm to assess extinction-induced plasticity, and 4) the combination of extinction and attention, two core mechanisms hypothesized to increase risk for PTSD, in the same sample. We expect this project to further the NIMH mission through the use of RDoC indices grounded in basic science, translated to clinical indicators, and directly linked to empirically-determined interventions. Findings from this work will provide new knowledge aiding early identification of trauma-exposed individuals most-at risk for chronic PTSD, and potentially targets for early intervention.