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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 Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms(Society for Neuroscience, 2022) Tanriverdi, Büşra; Gregory, David F.; Olino, Thomas M.; Ely, Timothy D.; Harnett, Nathaniel G.; van Rooij, Sanne J. H.; Lebois, Lauren A. M.; Seligowski, Antonia V.; Jovanovic, Tanja; Ressler, Kerry J.; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Bollen, Kenneth A.; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Kurz, Michael C.; McGrath, Meghan E.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Datner, Elizabeth M.; Pearson, Claire; Domeier, Robert M.; Rathlev, Niels K.; O'Neil, Brian J.; Sanchez, Leon D.; Bruce, Steven E.; Miller, Mark W.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Sheridan, John F.; Smoller, Jordan W.; Harte, Steven E.; Elliott, James M.; McLean, Samuel A.; Kessler, Ronald C.; Koenen, Karestan C.; Stevens, Jennifer S.; Murty, Vishnu P.; Emergency Medicine, School of MedicineHippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of Fear Potentiated Startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal. Significance Statement: Alterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on non-trauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk.Item Persistent Dissociation and Its Neural Correlates in Predicting Outcomes After Trauma Exposure(American Psychiatric Association, 2022) Lebois, Lauren A. M.; Harnett, Nathaniel G.; van Rooij, Sanne J. H.; Ely, Timothy D.; Jovanovic, Tanja; Bruce, Steven E.; House, Stacey L.; Ravichandran, Caitlin; Dumornay, Nathalie M.; Finegold, Katherine E.; Hill, Sarah B.; Merker, Julia B.; Phillips, Karlye A.; Beaudoin, Francesca L.; An, Xinming; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Swor, Robert A.; McGrath, Meghan E.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Datner, Elizabeth M.; Chang, Anna M.; Pearson, Claire; Domeier, Robert M.; Rathlev, Niels K.; O'Neil, Brian J.; Sergot, Paulina; Sanchez, Leon D.; Miller, Mark W.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Sheridan, John F.; Smoller, Jordan W.; Luna, Beatriz; Harte, Steven E.; Elliott, James M.; Kessler, Ronald C.; Koenen, Karestan C.; McLean, Samuel A.; Stevens, Jennifer S.; Ressler, Kerry J.; Emergency Medicine, School of MedicineObjective: Dissociation, a disruption or discontinuity in psychological functioning, is often linked with worse psychiatric symptoms; however, the prognostic value of dissociation after trauma is inconsistent. Determining whether trauma-related dissociation is uniquely predictive of later outcomes would enable early identification of at-risk trauma populations. The authors conducted the largest prospective longitudinal biomarker study of persistent dissociation to date to determine its predictive capacity for adverse psychiatric outcomes following acute trauma. Methods: All data were part of the Freeze 2 data release from the Advancing Understanding of Recovery After Trauma (AURORA) study. Study participants provided self-report data about persistent derealization (N=1,464), a severe type of dissociation, and completed a functional MRI emotion reactivity task and resting-state scan 2 weeks posttrauma (N=145). Three-month follow-up reports were collected of posttraumatic stress, depression, pain, anxiety symptoms, and functional impairment. Results: Derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activation in the emotion reactivity task and decreased resting-state vmPFC connectivity with the cerebellum and orbitofrontal cortex. In separate analyses, brain-based and self-report measures of persistent derealization at 2 weeks predicted worse 3-month posttraumatic stress symptoms, distinct from the effects of childhood maltreatment history and current posttraumatic stress symptoms. Conclusions: The findings suggest that persistent derealization is both an early psychological and biological marker of worse later psychiatric outcomes. The neural correlates of trauma-related dissociation may serve as potential targets for treatment engagement to prevent posttraumatic stress disorder. These results underscore dissociation assessment as crucial following trauma exposure to identify at-risk individuals, and they highlight an unmet clinical need for tailored early interventions.Item Prior histories of posttraumatic stress disorder and major depression and their onset and course in the three months after a motor vehicle collision in the AURORA study(Wiley, 2022) Joormann, Jutta; Ziobrowski, Hannah N.; King, Andrew J.; Gildea, Sarah M.; Lee, Sue; Sampson, Nancy A.; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Stevens, Jennifer S.; Zeng, Donglin; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Bollen, Kenneth A.; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; McGrath, Meghan E.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Chang, Anna M.; Pearson, Claire; Peak, David A.; Domeier, Robert M.; Rathlev, Niels K.; O'Neil, Brian J.; Sanchez, Leon D.; Bruce, Steven E.; Miller, Mark W.; Pietrzak, Robert H.; Barch, Deanna M.; Pizzagalli, Diego A.; Harte, Steven E.; Elliott, James M.; Koenen, Karestan C.; McLean, Samuel A.; Kessler, Ronald C.; Emergency Medicine, School of MedicineBackground: A better understanding of the extent to which prior occurrences of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) predict psychopathological reactions to subsequent traumas might be useful in targeting posttraumatic preventive interventions. Methods: Data come from 1306 patients presenting to 29 U.S. emergency departments (EDs) after a motor vehicle collision (MVC) in the advancing understanding of recovery after trauma study. Patients completed self-reports in the ED and 2-weeks, 8-weeks, and 3-months post-MVC. Associations of pre-MVC probable PTSD and probable MDE histories with subsequent 3-months post-MVC probable PTSD and probable MDE were examined along with mediation through intervening peritraumatic, 2-, and 8-week disorders. Results: 27.6% of patients had 3-month post-MVC probable PTSD and/or MDE. Pre-MVC lifetime histories of these disorders were not only significant (relative risk = 2.6-7.4) but were dominant (63.1% population attributable risk proportion [PARP]) predictors of this 3-month outcome, with 46.6% prevalence of the outcome among patients with pre-MVC disorder histories versus 9.9% among those without such histories. The associations of pre-MVC lifetime disorders with the 3-month outcome were mediated largely by 2- and 8-week probable PTSD and MDE (PARP decreasing to 22.8% with controls for these intervening disorders). Decomposition showed that pre-MVC lifetime histories predicted both onset and persistence of these intervening disorders as well as the higher conditional prevalence of the 3-month outcome in the presence of these intervening disorders. Conclusions: Assessments of pre-MVC PTSD and MDE histories and follow-ups at 2 and 8 weeks could help target early interventions for psychopathological reactions to MVCs.Item Prior Sexual Trauma Exposure Impacts Posttraumatic Dysfunction and Neural Circuitry Following a Recent Traumatic Event in the AURORA Study(Elsevier, 2023-02-16) Rowland, Grace E.; Roeckner, Alyssa; Ely, Timothy D.; Lebois, Lauren A. M.; van Rooij, Sanne J. H.; Bruce, Steven E.; Jovanovic, Tanja; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Kurz, Michael C.; Gentile, Nina T.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Harris, Erica; Pearson, Claire; Merchant, Roland C.; Domeier, Robert M.; Rathlev, Niels K.; Sergot, Paulina; Sanchez, Leon D.; Miller, Mark W.; Pietrzak, Robert H.; Joormann, Jutta; Pizzagalli, Diego A.; Sheridan, John F.; Smoller, Jordan W.; Harte, Steven E.; Elliott, James M.; Kessler, Ronald C.; Koenen, Karestan C.; McLean, Samuel A.; Ressler, Kerry J.; Stevens, Jennifer S.; Harnett, Nathaniel G.; Emergency Medicine, School of MedicineBackground: Prior sexual trauma (ST) is associated with greater risk for posttraumatic stress disorder after a subsequent traumatic event; however, the underlying neurobiological mechanisms remain opaque. We investigated longitudinal posttraumatic dysfunction and amygdala functional dynamics following admission to an emergency department for new primarily nonsexual trauma in participants with and without previous ST. Methods: Participants (N = 2178) were recruited following acute trauma exposure (primarily motor vehicle collision). A subset (n = 242) completed magnetic resonance imaging that included a fearful faces task and a resting-state scan 2 weeks after the trauma. We investigated associations between prior ST and several dimensions of posttraumatic symptoms over 6 months. We further assessed amygdala activation and connectivity differences between groups with or without prior ST. Results: Prior ST was associated with greater posttraumatic depression (F1,1120 = 28.35, p = 1.22 × 10-7, ηp2 = 0.06), anxiety (F1,1113 = 17.43, p = 3.21 × 10-5, ηp2 = 0.05), and posttraumatic stress disorder (F1,1027 = 11.34, p = 7.85 × 10-4, ηp2 = 0.04) severity and more maladaptive beliefs about pain (F1,1113 = 8.51, p = .004, ηp2 = 0.02) but was not related to amygdala reactivity to fearful versus neutral faces (all ps > .05). A secondary analysis revealed an interaction between ST and lifetime trauma load on the left amygdala to visual cortex connectivity (peak Z value: -4.41, corrected p < .02). Conclusions: Findings suggest that prior ST is associated with heightened posttraumatic dysfunction following a new trauma exposure but not increased amygdala activity. In addition, ST may interact with lifetime trauma load to alter neural circuitry in visual processing regions following acute trauma exposure. Further research should probe the relationship between trauma type and visual circuitry in the acute aftermath of trauma.Item A prospective examination of sex differences in posttraumatic autonomic functioning(Elsevier, 2021-08-21) Seligowski, Antonia V.; Steuber, Elizabeth R.; Hinrichs, Rebecca; Reda, Mariam H.; Wiltshire, Charis N.; Wanna, Cassandra P.; Winters, Sterling J.; Phillips, Karlye A.; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Stevens, Jennifer S.; Zeng, Donglin; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Bollen, Kenneth A.; Guffanti, Guia; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Kurz, Michael C.; Murty, Vishnu P.; McGrath, Meghan E.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Datner, Elizabeth M.; Chang, Anna M.; Pearson, Claire; Peak, David A.; Merchant, Roland C.; Domeier, Robert M.; Rathlev, Niels K.; O'Neil, Brian J.; Sanchez, Leon D.; Bruce, Steven E.; Miller, Mark W.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Sheridan, John F.; Luna, Beatriz; Harte, Steven E.; Elliott, James M.; Koenen, Karestan C.; Kessler, Ronald C.; McLean, Samuel A.; Ressler, Kerry J.; Jovanovic, Tanja; Emergency Medicine, School of MedicineBackground: Cross-sectional studies have found that individuals with posttraumatic stress disorder (PTSD) exhibit deficits in autonomic functioning. While PTSD rates are twice as high in women compared to men, sex differences in autonomic functioning are relatively unknown among trauma-exposed populations. The current study used a prospective design to examine sex differences in posttraumatic autonomic functioning. Methods: 192 participants were recruited from emergency departments following trauma exposure (Mean age = 35.88, 68.2% female). Skin conductance was measured in the emergency department; fear conditioning was completed two weeks later and included measures of blood pressure (BP), heart rate (HR), and high frequency heart rate variability (HF-HRV). PTSD symptoms were assessed 8 weeks after trauma. Results: 2-week systolic BP was significantly higher in men, while 2-week HR was significantly higher in women, and a sex by PTSD interaction suggested that women who developed PTSD demonstrated the highest HR levels. Two-week HF-HRV was significantly lower in women, and a sex by PTSD interaction suggested that women with PTSD demonstrated the lowest HF-HRV levels. Skin conductance response in the emergency department was associated with 2-week HR and HF-HRV only among women who developed PTSD. Conclusions: Our results indicate that there are notable sex differences in autonomic functioning among trauma-exposed individuals. Differences in sympathetic biomarkers (BP and HR) may have implications for cardiovascular disease risk given that sympathetic arousal is a mechanism implicated in this risk among PTSD populations. Future research examining differential pathways between PTSD and cardiovascular risk among men versus women is warranted.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.Item Structural covariance of the ventral visual stream predicts posttraumatic intrusion and nightmare symptoms: a multivariate data fusion analysis(Springer Nature, 2022-08-08) Harnett, Nathaniel G.; Finegold, Katherine E.; Lebois, Lauren A.M.; van Rooij, Sanne J.H.; Ely, Timothy D.; Murty, Vishnu P.; Jovanovic, Tanja; Bruce, Steven 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.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Kurz, Michael C.; Swor, Robert A.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Harris, Erica; Chang, Anna M.; Pearson, Claire; Peak, David A.; Domeier, Robert M.; Rathlev, Niels K.; O'Neil, Brian J.; Sergot, Paulina; Sanchez, Leon D.; Miller, Mark W.; 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 A.; Nickerson, Lisa D.; Ressler, Kerry J.; Stevens, Jennifer S.; Emergency Medicine, School of MedicineVisual components of trauma memories are often vividly re-experienced by survivors with deleterious consequences for normal function. Neuroimaging research on trauma has primarily focused on threat-processing circuitry as core to trauma-related dysfunction. Conversely, limited attention has been given to visual circuitry which may be particularly relevant to posttraumatic stress disorder (PTSD). Prior work suggests that the ventral visual stream is directly related to the cognitive and affective disturbances observed in PTSD and may be predictive of later symptom expression. The present study used multimodal magnetic resonance imaging data (n = 278) collected two weeks after trauma exposure from the AURORA study, a longitudinal, multisite investigation of adverse posttraumatic neuropsychiatric sequelae. Indices of gray and white matter were combined using data fusion to identify a structural covariance network (SCN) of the ventral visual stream 2 weeks after trauma. Participant's loadings on the SCN were positively associated with both intrusion symptoms and intensity of nightmares. Further, SCN loadings moderated connectivity between a previously observed amygdala-hippocampal functional covariance network and the inferior temporal gyrus. Follow-up MRI data at 6 months showed an inverse relationship between SCN loadings and negative alterations in cognition in mood. Further, individuals who showed decreased strength of the SCN between 2 weeks and 6 months had generally higher PTSD symptom severity over time. The present findings highlight a role for structural integrity of the ventral visual stream in the development of PTSD. The ventral visual stream may be particularly important for the consolidation or retrieval of trauma memories and may contribute to efficient reactivation of visual components of the trauma memory, thereby exacerbating PTSD symptoms. Potentially chronic engagement of the network may lead to reduced structural integrity which becomes a risk factor for lasting PTSD symptoms.Item Structural inequities contribute to racial/ethnic differences in neurophysiological tone, but not threat reactivity, after trauma exposure(Springer Nature, 2023) Harnett, Nathaniel G.; Fani, Negar; Carter, Sierra; Sanchez, Leon D.; Rowland, Grace E.; Davie, William M.; Guzman, Camilo; Lebois, Lauren A. M.; Ely, Timothy D.; van Rooij, Sanne J. H.; Seligowski, Antonia V.; Winters, Sterling; Grasser, Lana R.; Musey, Paul I., Jr.; Seamon, Mark J.; 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.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Swor, Robert A.; Hudak, Lauren A.; Pascual, Jose L.; Harris, Erica; Chang, Anna M.; Pearson, Claire; Peak, David A.; Merchant, Roland C.; Domeier, Robert M.; Rathlev, Niels K.; Bruce, Steven E.; Miller, Mark W.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Harte, Steven E.; Elliott, James M.; Kessler, Ronald C.; Koenen, Karestan C.; McLean, Samuel A.; Jovanovic, Tanja; Stevens, Jennifer S.; Ressler, Kerry J.; Emergency Medicine, School of MedicineConsiderable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.Item Use of serial smartphone-based assessments to characterize diverse neuropsychiatric symptom trajectories in a large trauma survivor cohort(Springer Nature, 2023-01-07) Beaudoin, Francesca L.; An, Xinming; Basu, Archana; Ji, Yinyao; Liu, Mochuan; Kessler, Ronald C.; Doughtery, Robert F.; Zeng, Donglin; Bollen, Kenneth A.; House, Stacey L.; Stevens, Jennifer S.; Neylan, Thomas C.; Clifford, Gari D.; Jovanovic, Tanja; Linnstaedt, Sarah D.; Germine, Laura T.; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Kurz, Michael C.; Swor, Robert A.; Murty, Vishnu P.; McGrath, Meghan E.; Hudak, Lauren A.; Pascual, Jose L.; Datner, Elizabeth M.; Chang, Anna M.; Pearson, Claire; Peak, David A.; Merchant, Roland C.; Domeier, Robert M.; Rathlev, Niels K.; O' Neil, Brian J.; Sergot, Paulina; Sanchez, Leon D.; Bruce, Steven E.; Baker, Justin T.; Joormann, Jutta; Miller, Mark W.; Pietrzak, Robert H.; Barch, Deanna M.; Pizzagalli, Diego A.; Sheridan, John F.; Smoller, Jordan W.; Harte, Steven E.; Elliott, James M.; Koenen, Karestan C.; Ressler, Kerry J.; McLean, Samuel A.; Emergency Medicine, School of MedicineThe authors sought to characterize adverse posttraumatic neuropsychiatric sequelae (APNS) symptom trajectories across ten symptom domains (pain, depression, sleep, nightmares, avoidance, re-experiencing, anxiety, hyperarousal, somatic, and mental/fatigue symptoms) in a large, diverse, understudied sample of motor vehicle collision (MVC) survivors. More than two thousand MVC survivors were enrolled in the emergency department (ED) and completed a rotating battery of brief smartphone-based surveys over a 2-month period. Measurement models developed from survey item responses were used in latent growth curve/mixture modeling to characterize homogeneous symptom trajectories. Associations between individual trajectories and pre-trauma and peritraumatic characteristics and traditional outcomes were compared, along with associations within and between trajectories. APNS across all ten symptom domains were common in the first two months after trauma. Many risk factors and associations with high symptom burden trajectories were shared across domains. Both across and within traditional diagnostic boundaries, APNS trajectory intercepts, and slopes were substantially correlated. Across all domains, symptom severity in the immediate aftermath of trauma (trajectory intercepts) had the greatest influence on the outcome. An interactive data visualization tool was developed to allow readers to explore relationships of interest between individual characteristics, symptom trajectories, and traditional outcomes ( http://itr.med.unc.edu/aurora/parcoord/ ). Individuals presenting to the ED after MVC commonly experience a broad constellation of adverse posttraumatic symptoms. Many risk factors for diverse APNS are shared. Individuals diagnosed with a single traditional outcome should be screened for others. The utility of multidimensional categorizations that characterize individuals across traditional diagnostic domains should be explored.