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.
Identifying trauma-exposed individuals most at risk for long-term post-trauma and anxiety symptoms is a pressing public health problem. This work seeks to identify dysregulation in neural circuitry supporting cognitive and affective processes two weeks after a traumatic event that predicts PTSD and other post-trauma symptom severity six to twenty-four months later. These data will advance our understanding of neurobiological factors associated with vulnerability to specific trauma-related pathology and provide an important step toward identifying appropriate early interventions in the wake of trauma.
