The AURORA Study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure

Abstract

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.

Figure 1.

Trauma survivors with adverse posttraumatic neuropsychiatric sequelae (APNS) have traditionally been evaluated in a siloed, syndrome-centered fashion (panel A), in which individual syndromes are separately diagnosed and managed. AURORA seeks to provide data to help support the ongoing transition to both a more biologically-anchored and patient-centered approach, in which discrete types of brain dysfunction (panel B) are evaluated, and the influence of the overall multidimensional context is considered in the evaluation of therapeutic targets and in understanding the response to treatments targeting specific areas of dysfunction.

Figure 2.

The goal of the AURORA Study is to generate a rich, multilayered biobehavioral library of data for each of the most common discrete types of brain/neurobiological dysfunction experienced by trauma survivors (Panel A). It is hoped that these data will be valuable in achieving a range of goals, including identifying trajectories of predictive biomarkers, understanding changes in neurobiology during onset, identifying diagnostic biomarkers, and/or understanding markers of worsening symptoms vs. recovery (Panel B).

Figure 3.

Study design overview (n=5,000). In-person evaluation includes blood draw, fMRI, and psychophysical assessment.

Figure 4.

Overview of AURORA Study biological specimens collected. DNA, RNA, and plasma samples are collected from all participants (n=5,000 target enrollment) in the Emergency Department (ED) in the early aftermath of trauma exposure. Serial saliva samples are collected from a subset of participants (n≤2,000) in the ED and 1, 2, 3, and 4 weeks following enrollment. DNA, RNA, and plasma are collected again on a subset of participants at the 2 week and 6 month deep phenotyping sessions (n≤800) and at the 6 month timepoint via individual blood draw (n≤2,200). ACD tubes (for the generation of lymphoproliferative cell lines) are collected on a small subset of participants at deep phenotyping sessions.