Acute Neurocognitive-affective Predictors of Chronic Post-trauma Outcomes

 描述(由申请人提供)：创伤暴露非常常见，并增加了一系列负面健康后果的风险，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，至关重要的是确定创伤后急性风险因素，预测慢性创伤后应激障碍和其他创伤后不良后果。虽然在这方面的努力取得了一些进展，但事实证明，很难确定最近受到创伤的个人面临长期创伤后适应不良的风险。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素，更重要的是，确定预测慢性创伤后应激障碍以及包括抑郁和药物使用问题在内的其他症状的创伤后急性措施。我们将评估三个过程的预测效用，这三个过程1)植根于基础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，以及4)在我们的初步数据中显示前景。利用我们在威斯康星医学院1级创伤服务中接触到大量患者的独特途径，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)的纵向评估，并对这些症状进行基于RDoC的预测。在创伤暴露的两周内，我们将评估基于RDoC的过程指数，假设这些过程会增加创伤后应激症状，包括条件恐惧的消退和保持(急性威胁/恐惧，持续威胁)，威胁过滤受损(注意控制)，以及对威胁的注意偏差(持续威胁)。在暴露后六个月，我们将再次对这些过程进行多级别评估，并测量创伤后应激障碍和其他相关症状的症状。除了这两个主要评估点(都涉及神经成像)，我们还将收集暴露后长达24个月的多个点的认知和情感功能以及症状严重程度指数。我们将在两周内对220名因急性创伤后症状而过度抽样的人进行扫描，目标是在6个月内最终抽样200人，并在24个月内最终抽样150人。我们假设，恐惧消退、消退相关的可塑性(静息状态的变化)中的急性损伤 注意过滤和注意偏向将预示暴露后6至24个月的创伤后应激障碍症状升高。这项工作提供了几个关键的创新：1)对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)使用新的范式来评估灭绝诱导的可塑性，以及4)在同一样本中，两种核心机制--消退和注意力的结合--被认为会增加创伤后应激障碍的风险。我们期待这个项目通过使用以基础科学为基础、转化为临床指标并直接与经验确定的干预措施相联系的RDoC指数来推动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者最有可能患慢性创伤后应激障碍的风险，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.