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Item The AURORA Study: A Longitudinal, Multimodal Library of Brain Biology and Function after Traumatic Stress Exposure(Springer Nature, 2020-02) McLean, Samuel A.; Ressler, Kerry; Koenen, Karestan Chase; Neylan, Thomas; Germine, Laura; Jovanovic, Tanja; Clifford, Gari D.; Zeng, Donglin; An, Xinming; Linnstaedt, Sarah; Beaudoin, Francesca; House, Stacey; Bollen, Kenneth A.; Musey, Paul; Hendry, Phyllis; Jones, Christopher W.; Lewandowski, Christopher; Swor, Robert; Datner, Elizabeth; Mohiuddin, Kamran; Stevens, Jennifer S.; Storrow, Alan; Kurz, Michael Christopher; McGrath, Meghan E.; Fermann, Gregory J.; Hudak, Lauren A.; Gentile, Nina; Chang, Anna Marie; Peak, David A.; Pascual, Jose L.; Seamon, Mark J.; Sergot, Paulina; Peacock, W. Frank; Diercks, Deborah; Sanchez, Leon D.; Rathlev, Niels; Domeier, Robert; Haran, John Patrick; Pearson, Claire; Murty, Vishnu P.; Insel, Thomas R.; Dagum, Paul; Onnela, Jukka-Pekka; Bruce, Steven E.; Gaynes, Bradley N.; Joormann, Jutta; Miller, Mark W.; Pietrzak, Robert H.; Buysse, Daniel J.; Pizzagalli, Diego A.; Rauch, Scott L.; Harte, Steven E.; Young, Larry J.; Barch, Deanna M.; Lebois, Lauren A. M.; van Rooij, Sanne J. H.; Luna, Beatriz; Smoller, Jordan W.; Dougherty, Robert F.; Pace, Thaddeus W. W.; Binder, Elisabeth; Sheridan, John F.; Elliott, James M.; Basu, Archana; Fromer, Menachem; Parlikar, Tushar; Zaslavsky, Alan M.; Kessler, Ronald; Emergency Medicine, School of MedicineAdverse 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.Item Classification and Prediction of Post-Trauma Outcomes Related to PTSD Using Circadian Rhythm Changes Measured via Wrist-Worn Research Watch in a Large Longitudinal Cohort(IEEE, 2021) Cakmak, Ayse S.; Perez Alday, Erick A.; Da Poian, Giulia; Rad, Ali Bahrami; Metzler, Thomas J.; Neylan, Thomas C.; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Stevens, Jennifer S.; Zeng, Donglin; Linnstaedt, Sarah D.; Jovanovic, Tanja; Germine, Laura T.; Bollen, Kenneth A.; Rauch, Scott L.; Lewandowski, Christopher A.; Hendry, Phyllis L.; Sheikh, Sophia; Storrow, Alan B.; Musey, Paul I., Jr.; Haran, John P.; Jones, Christopher W.; Punches, Brittany E.; Swor, Robert A.; Gentile, Nina T.; McGrath, Meghan E.; Seamon, Mark J.; Mohiuddin, Kamran; Chang, Anna M.; Pearson, Claire; Domeier, Robert M.; Bruce, Steven E.; O’Neil, Brian J.; Rathlev, Niels K.; Sanchez, Leon D.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Harte, Steven E.; Elliott, James M.; Kessler, Ronald C.; Koenen, Karestan C.; Ressler, Kerry J.; Mclean, Samuel A.; Li, Qiao; Clifford, Gari D.; Emergency Medicine, School of MedicinePost-Traumatic Stress Disorder (PTSD) is a psychiatric condition resulting from threatening or horrifying events. We hypothesized that circadian rhythm changes, measured by a wrist-worn research watch are predictive of post-trauma outcomes. Approach: 1618 post-trauma patients were enrolled after admission to emergency departments (ED). Three standardized questionnaires were administered at week eight to measure post-trauma outcomes related to PTSD, sleep disturbance, and pain interference with daily life. Pulse activity and movement data were captured from a research watch for eight weeks. Standard and novel movement and cardiovascular metrics that reflect circadian rhythms were derived using this data. These features were used to train different classifiers to predict the three outcomes derived from week-eight surveys. Clinical surveys administered at ED were also used as features in the baseline models. Results: The highest cross-validated performance of research watch-based features was achieved for classifying participants with pain interference by a logistic regression model, with an area under the receiver operating characteristic curve (AUC) of 0.70. The ED survey-based model achieved an AUC of 0.77, and the fusion of research watch and ED survey metrics improved the AUC to 0.79. Significance: This work represents the first attempt to predict and classify post-trauma symptoms from passive wearable data using machine learning approaches that leverage the circadian desynchrony in a potential PTSD population.Item Neurocognition after motor vehicle collision and adverse post-traumatic neuropsychiatric sequelae within 8 weeks: Initial findings from the AURORA study(Elsevier, 2022) Germine, Laura T.; Joormann, Jutta; Passell, Eliza; Rutter, Lauren A.; Scheuer, Luke; Martini, Paolo; Hwang, Irving; Lee, Sue; Sampson, Nancy; Barch, Deanna M.; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Stevens, Jennifer S.; Zeng, Donglin; Linnstaedt, Sarah D.; Jovanovic, Tanja; Clifford, Gari D.; Neylan, Thomas C.; Rauch, Scott L.; Lewandowski, Christopher; Hendry, Phyllis L.; Sheikh, Sophia; Storrow, Alan B.; Musey, Paul I.; Jones, Christopher W.; Punches, Brittney E.; McGrath, Meghan E.; Pascual, Jose L.; Mohiuddin, Kamran; Pearson, Claire; Peak, David A.; Domeier, Robert M.; Bruce, Steven E.; Rathlev, Niels K.; Sanchez, Leon D.; Pietrzak, Robert H.; Pizzagalli, Diego A.; Harte, Steven E.; Elliott, James M.; Koenen, Karesten C.; Ressler, Kerry J.; McLean, Samuel A.; Kessler, Ronald C.; Emergency Medicine, School of MedicineBackground: Previous work has indicated that differences in neurocognitive functioning may predict the development of adverse post-traumatic neuropsychiatric sequelae (APNS). Such differences may be vulnerability factors or simply correlates of APNS-related symptoms. Longitudinal studies that measure neurocognitive functioning at the time of trauma are needed to determine whether such differences precede the development of APNS. Methods: Here, we present findings from a subsample of 666 ambulatory patients from the AURORA (Advancing Understanding of RecOvery afteR trumA) study. All patients presented to EDs after a motor vehicle collision (MVC). We examined associations of neurocognitive test performance shortly after MVC with peritraumatic symptoms in the ED and APNS (depression, post-traumatic stress, post-concussive symptoms, and pain) 2 weeks and 8 weeks later. Neurocognitive tests assessed processing speed, attention, verbal reasoning, memory, and social perception. Results: Distress in the ED was associated with poorer processing speed and short-term memory. Poorer short-term memory was also associated with depression at 2 weeks post-MVC, even after controlling for peritraumatic distress. Finally, higher vocabulary scores were associated with pain 2 weeks post-MVC. Limitations: Self-selection biases among those who present to the ED and enroll in the study limit generalizability. Also, it is not clear whether observed neurocognitive differences predate MVC exposure or arise in the immediate aftermath of MVC exposure. Conclusions: Our results suggest that processing speed and short-term memory may be useful predictors of trauma-related characteristics and the development of some APNS, making such measures clinically-relevant for identifying at-risk individuals.Item Prognostic neuroimaging biomarkers of trauma-related psychopathology: resting-state fMRI shortly after trauma predicts future PTSD and depression symptoms in the AURORA study(Springer Nature, 2021) Harnett, Nathaniel G.; van Rooij, Sanne J.H.; Ely, Timothy D.; Lebois, Lauren A.M.; Murty, Vishnu P.; Jovanovic, Tanja; Hill, Sarah B.; Dumornay, Nathalie M.; Merker, Julia B.; Bruce, Steve E.; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Zeng, Donglin; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Bollen, Kenneth A.; Rauch, Scott L.; Lewandowski, Christopher; Hendry, Phyllis L.; Sheikh, Sophia; Storrow, Alan B.; Musey, Paul I., Jr.; Haran, John P.; Jones, Christopher W.; Punches, Brittany E.; Swor, Robert A.; McGrath, Meghan E.; Pascual, Jose L.; Seamon, Mark J.; Mohiuddin, Kamran; Chang, Anna M.; Pearson, Claire; Peak, David A.; Domeier, Robert M.; Rathlev, Niels K.; Sanchez, Leon D.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Sheridan, John F.; Harte, Steven E.; Elliott, James M.; Kessler, Ronald C.; Koenen, Karestan C.; Mclean, Samuel; Ressler, Kerry J.; Stevens, Jennifer S.; Emergency Medicine, School of MedicineNeurobiological markers of future susceptibility to posttraumatic stress disorder (PTSD) may facilitate identification of vulnerable individuals in the early aftermath of trauma. Variability in resting-state networks (RSNs), patterns of intrinsic functional connectivity across the brain, has previously been linked to PTSD, and may thus be informative of PTSD susceptibility. The present data are part of an initial analysis from the AURORA study, a longitudinal, multisite study of adverse neuropsychiatric sequalae. Magnetic resonance imaging (MRI) data from 109 recently (i.e., ~2 weeks) traumatized individuals were collected and PTSD and depression symptoms were assessed at 3 months post trauma. We assessed commonly reported RSNs including the default mode network (DMN), central executive network (CEN), and salience network (SN). We also identified a proposed arousal network (AN) composed of a priori brain regions important for PTSD: the amygdala, hippocampus, mamillary bodies, midbrain, and pons. Primary analyses assessed whether variability in functional connectivity at the 2-week imaging timepoint predicted 3-month PTSD symptom severity. Left dorsolateral prefrontal cortex (DLPFC) to AN connectivity at 2 weeks post trauma was negatively related to 3-month PTSD symptoms. Further, right inferior temporal gyrus (ITG) to DMN connectivity was positively related to 3-month PTSD symptoms. Both DLPFC-AN and ITG-DMN connectivity also predicted depression symptoms at 3 months. Our results suggest that, following trauma exposure, acutely assessed variability in RSN connectivity was associated with PTSD symptom severity approximately two and a half months later. However, these patterns may reflect general susceptibility to posttraumatic dysfunction as the imaging patterns were not linked to specific disorder symptoms, at least in the subacute/early chronic phase. The present data suggest that assessment of RSNs in the early aftermath of trauma may be informative of susceptibility to posttraumatic dysfunction, with future work needed to understand neural markers of long-term (e.g., 12 months post trauma) dysfunction. Furthermore, these findings are consistent with neural models suggesting that decreased top-down cortico-limbic regulation and increased network-mediated fear generalization may contribute to ongoing dysfunction in the aftermath of trauma.Item Socio-demographic and trauma-related predictors of depression within eight weeks of motor vehicle collision in the AURORA study(Cambridge University Press, 2022) Joormann, Jutta; McLean, Samuel A.; Beaudoin, Francesca L.; An, Xinming; Stevens, Jennifer S.; Zeng, Donglin; Neylan, Thomas C.; Clifford, Gari; Linnstaedt, Sarah D.; Germine, Laura T.; Rauch, Scott L.; Musey, Paul I.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Fermann, Gregory; Hudak, Lauren A.; Mohiuddin, Kamran; Murty, Vishnu; McGrath, Meghan E.; Haran, John P.; Pascual, Jose; Seamon, Mark; Peak, David A.; Pearson, Claire; Domeier, Robert M.; Sergot, Paulina; Merchant, Roland; Sanchez, Leon D.; Rathlev, Niels K.; Peacock, William F.; Bruce, Steven E.; Barch, Deanna; Pizzagalli, Diego A.; Luna, Beatriz; Harte, Steven E.; Hwang, Irving; Lee, Sue; Sampson, Nancy; Koenen, Karestan C.; Ressler, Kerry J.; Kessler, Ronald C.; Emergency Medicine, School of MedicineBackground: This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. Methods: We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression. Results: Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma. Conclusions: These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.Item Socio-demographic and trauma-related predictors of PTSD within 8 weeks of a motor vehicle collision in the AURORA study(Springer Nature, 2021-07) Kessler, Ronald C.; Ressler, Kerry J.; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Stevens, Jennifer S.; Zeng, Donglin; Neylan, Thomas C.; Linnstaedt, Sarah D.; Germine, Laura T.; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Storrow, Alan B.; Jones, Christopher W.; Punches, Brittany E.; Datner, Elizabeth M.; Mohiuddin, Kamran; Gentile, Nina T.; McGrath, Meghan E.; van Rooij, Sanne J.; Hudak, Lauren A.; Haran, John P.; Peak, David A.; Domeier, Robert M.; Pearson, Claire; Sanchez, Leon D.; Rathlev, Niels K.; Peacock, William F.; Bruce, Steven E.; Miller, Mark W.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Sheridan, John F.; Smoller, Jordan W.; Pace, Thaddeus W.W.; Harte, Steven E.; Elliott, James M.; Harnett, Nathaniel G.; Lebois, Lauren A.M.; Hwang, Irving; Sampson, Nancy A.; Koenen, Karestan C.; McLean, Samuel A.; Emergency Medicine, School of MedicineThis is the initial report of results from the AURORA multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. We focus on n = 666 participants presenting to EDs following a motor vehicle collision (MVC) and examine associations of participant socio-demographic and participant-reported MVC characteristics with 8-week posttraumatic stress disorder (PTSD) adjusting for pre-MVC PTSD and mediated by peritraumatic symptoms and 2-week acute stress disorder (ASD). Peritraumatic Symptoms, ASD, and PTSD were assessed with self-report scales. Eight-week PTSD prevalence was relatively high (42.0%) and positively associated with participant sex (female), low socioeconomic status (education and income), and several self-report indicators of MVC severity. Most of these associations were entirely mediated by peritraumatic symptoms and, to a lesser degree, ASD, suggesting that the first 2 weeks after trauma may be a uniquely important time period for intervening to prevent and reduce risk of PTSD. This observation, coupled with substantial variation in the relative strength of mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated with more in-depth analyses of the rich and evolving AURORA data.