Browsing by Author "Sheridan, John F."
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Item Anxiety sensitivity as a transdiagnostic risk factor for trajectories of adverse posttraumatic neuropsychiatric sequelae in the AURORA study(Elsevier, 2022-12) Short , Nicole A.; van Rooij , Sanne J. H.; Murty, Vishnu P.; Stevens, Jennifer S.; An , Xinming; Ji , Yinyao; McLean , Samuel A.; House , Stacey L.; Beaudoin, Francesca L.; Zeng, Donglin; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Bollen, Kenneth A.; Rauch , Scott L.; Haran , John P.; Lewandowski, Christopher; Musey Jr., Paul I.; 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.; 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.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli , Diego A.; Sheridan, John F.; Smoller, Jordan W.; Harte, Steven E.; Elliott, James M.; Kessler, Ronald C.; Koenen, Karestan C .; Jovanovic , Tanja; Emergency Medicine, School of MedicineAnxiety sensitivity, or fear of anxious arousal, is cross-sectionally associated with a wide array of adverse posttraumatic neuropsychiatric sequelae, including symptoms of posttraumatic stress disorder, depression, anxiety, sleep disturbance, pain, and somatization. The current study utilizes a large-scale, multi-site, prospective study of trauma survivors presenting to emergency departments. Hypotheses tested whether elevated anxiety sensitivity in the immediate posttrauma period is associated with more severe and persistent trajectories of common adverse posttraumatic neuropsychiatric sequelae in the eight weeks posttrauma. Participants from the AURORA study (n = 2,269 recruited from 23 emergency departments) completed self-report assessments over eight weeks posttrauma. Associations between heightened anxiety sensitivity and more severe and/or persistent trajectories of trauma-related symptoms identified by growth mixture modeling were analyzed. Anxiety sensitivity assessed two weeks posttrauma was associated with severe and/or persistent posttraumatic stress, depression, anxiety, sleep disturbance, pain, and somatic symptoms in the eight weeks posttrauma. Effect sizes were in the small to medium range in multivariate models accounting for various demographic, trauma-related, pre-trauma mental health-related, and personality-related factors. Anxiety sensitivity may be a useful transdiagnostic risk factor in the immediate posttraumatic period identifying individuals at risk for the development of adverse posttraumatic neuropsychiatric sequelae. Further, considering anxiety sensitivity is malleable via brief intervention, it could be a useful secondary prevention target. Future research should continue to evaluate associations between anxiety sensitivity and trauma-related pathology.Item Associations of Alcohol and Cannabis Use with Change in Posttraumatic Stress Disorder and Depression Symptoms Over Time in Recently Trauma-exposed Individuals(Cambridge University Press, 2024) Hinojosa, Cecilia A.; Liew, Amanda; An, Xinming; Stevens, Jennifer S.; Basu, Archana; van Rooij, Sanne J. H.; House, Stacey L.; Beaudoin, Francesca L.; Zeng, Donglin; 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.; 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.; Datner, Elizabeth M.; Chang, Anna M.; Pearson, Claire; Peak, David A.; Merchant, Roland C.; Domeier, Robert M.; Rathlev, Niels K.; Sergot, Paulina; Sanchez, Leon D.; Bruce, Steven E.; Miller, Mark W.; Pietrzak, Robert H.; Joormann, Jutta; Pizzagalli, Diego A.; Sheridan, John F.; Harte, Steven E.; Elliott, James M.; Kessler, Ronald C.; Koenen, Karestan C.; McLean, Samuel A.; Ressler, Kerry J.; Fani, Negar; Emergency Medicine, School of MedicineBackground: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. Methods: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. Results: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. Conclusions: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.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 Brain-Based Biotypes of Psychiatric Vulnerability in the Acute Aftermath of Trauma(American Psychiatric Association, 2021) Stevens, Jennifer S.; Harnett, Nathaniel G.; Lebois, Lauren A.M.; van Rooij, Sanne J.H.; Ely, Timothy D.; Roeckner, Alyssa; Vincent, Nico; Beaudoin, Francesca L.; An, Xinming; Zeng, Donglin; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Rauch, Scott L.; Lewandowski, Christopher; Storrow, Alan B.; Hendry, Phyllis L.; Sheikh, Sophia; Musey, Paul I., Jr.; Haran, John P.; Jones, Christopher W.; Punches, Brittany E.; Lyons, Michael S.; Kurz, Michael C.; McGrath, Meghan E.; Pascual, Jose L.; Datner, Elizabeth M.; Chang, Anna M.; Pearson, Claire; Peak, David A.; Domeier, Robert M.; O'Neil, Brian J.; Rathlev, Niels K.; Sanchez, Leon D.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Sheridan, John F.; Luna, Beatriz; Harte, Steven E.; Elliott, James M.; Murty, Vishnu P.; Jovanovic, Tanja; Bruce, Steven E.; House, Stacey L.; Kessler, Ronald C.; Koenen, Karestan C.; McLean, Samuel A.; Ressler, Kerry J.; Emergency Medicine, School of MedicineObjective: Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic longitudinal study of trauma exposure and related mental health outcomes to identify neurobiological predictors of risk, resilience, and different symptom presentations. Methods: A total of 146 participants (discovery cohort: N=69; internal replication cohort: N=77) were recruited from emergency departments within 72 hours of a trauma and followed for the next 6 months with a survey, MRI, and physiological assessments. Results: Task-based functional MRI 2 weeks after a motor vehicle collision identified four clusters of individuals based on profiles of neural activity reflecting threat reactivity, reward reactivity, and inhibitory engagement. Three clusters were replicated in an independent sample with a variety of trauma types. The clusters showed different longitudinal patterns of posttrauma symptoms. Conclusions: These findings provide a novel characterization of heterogeneous stress responses shortly after trauma exposure, identifying potential neuroimaging-based biotypes of trauma resilience and psychopathology.Item Derivation and Validation of a Brief Emergency Department-Based Prediction Tool for Posttraumatic Stress After Motor Vehicle Collision(Elsevier, 2023) Jones, Christopher W.; An, Xinming; Ji, Yinyao; Liu, Mochuan; Zeng, Donglin; House, Stacey L.; Beaudoin, Francesca L.; Stevens, Jennifer S.; Neylan, Thomas C.; Clifford, Gari D.; Jovanovic, Tanja; 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; Punches, Brittany E.; Lyons, Michael S.; Kurz, Michael C.; Swor, Robert A.; McGrath, Meghan E.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Datner, Elizabeth M.; Harris, Erica; 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.; 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.; Koenen, Karestan C.; Ressler, Kerry J.; Kessler, Ronald C.; McLean, Samuel A.; Emergency Medicine, School of MedicineStudy objective: To derive and initially validate a brief bedside clinical decision support tool that identifies emergency department (ED) patients at high risk of substantial, persistent posttraumatic stress symptoms after a motor vehicle collision. Methods: Derivation (n=1,282, 19 ED sites) and validation (n=282, 11 separate ED sites) data were obtained from adults prospectively enrolled in the Advancing Understanding of RecOvery afteR traumA study who were discharged from the ED after motor vehicle collision-related trauma. The primary outcome was substantial posttraumatic stress symptoms at 3 months (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5 ≥38). Logistic regression derivation models were evaluated for discriminative ability using the area under the curve and the accuracy of predicted risk probabilities (Brier score). Candidate posttraumatic stress predictors assessed in these models (n=265) spanned a range of sociodemographic, baseline health, peritraumatic, and mechanistic domains. The final model selection was based on performance and ease of administration. Results: Significant 3-month posttraumatic stress symptoms were common in the derivation (27%) and validation (26%) cohort. The area under the curve and Brier score of the final 8-question tool were 0.82 and 0.14 in the derivation cohort and 0.76 and 0.17 in the validation cohort. Conclusion: This simple 8-question tool demonstrates promise to risk-stratify individuals with substantial posttraumatic stress symptoms who are discharged to home after a motor vehicle collision. Both external validation of this instrument, and work to further develop more accurate tools, are needed. Such tools might benefit public health by enabling the conduct of preventive intervention trials and assisting the growing number of EDs that provide services to trauma survivors aimed at promoting psychological recovery.Item Development and Validation of a Model to Predict Posttraumatic Stress Disorder and Major Depression After a Motor Vehicle Collision(American Medical Association, 2021) Ziobrowski, Hannah N.; Kennedy, Chris J.; Ustun, Berk; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Zeng, Donglin; Bollen, Kenneth A.; Petukhova, Maria; Sampson, Nancy A.; Puac-Polanco, Victor; Lee, Sue; Koenen, Karestan C.; Ressler, Kerry J.; McLean, Samuel A.; Kessler, Ronald C.; AURORA Consortium; 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.; Lyons, Michael S.; Murty, Vishnu P.; McGrath, Meghan E.; Pascual, Jose L.; Seamon, Mark J.; Datner, Elizabeth M.; Chang, Anna M.; Pearson, Claire; Peak, David A.; Jambaulikar, Guruprasad; Merchant, Roland C.; Domeier, Robert M.; Rathlev, Niels K.; O'Neil, Brian J.; Sergot, Paulina; Sanchez, Leon D.; Bruce, Steven E.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Sheridan, John F.; Harte, Steven E.; Elliott, James M.; van Rooij, Sanne J.H.; Emergency Medicine, School of MedicineImportance: A substantial proportion of the 40 million people in the US who present to emergency departments (EDs) each year after traumatic events develop posttraumatic stress disorder (PTSD) or major depressive episode (MDE). Accurately identifying patients at high risk in the ED would facilitate the targeting of preventive interventions. Objectives: To develop and validate a prediction tool based on ED reports after a motor vehicle collision to predict PTSD or MDE 3 months later. Design, setting, and participants: The Advancing Understanding of Recovery After Trauma (AURORA) study is a longitudinal study that examined adverse posttraumatic neuropsychiatric sequalae among patients who presented to 28 US urban EDs in the immediate aftermath of a traumatic experience. Enrollment began on September 25, 2017. The 1003 patients considered in this diagnostic/prognostic report completed 3-month assessments by January 31, 2020. Each patient received a baseline ED assessment along with follow-up self-report surveys 2 weeks, 8 weeks, and 3 months later. An ensemble machine learning method was used to predict 3-month PTSD or MDE from baseline information. Data analysis was performed from November 1, 2020, to May 31, 2021. Main outcomes and measures: The PTSD Checklist for DSM-5 was used to assess PTSD and the Patient Reported Outcomes Measurement Information System Depression Short-Form 8b to assess MDE. Results: A total of 1003 patients (median [interquartile range] age, 34.5 [24-43] years; 715 [weighted 67.9%] female; 100 [weighted 10.7%] Hispanic, 537 [weighted 52.7%] non-Hispanic Black, 324 [weighted 32.2%] non-Hispanic White, and 42 [weighted 4.4%] of non-Hispanic other race or ethnicity were included in this study. A total of 274 patients (weighted 26.6%) met criteria for 3-month PTSD or MDE. An ensemble machine learning model restricted to 30 predictors estimated in a training sample (patients from the Northeast or Midwest) had good prediction accuracy (mean [SE] area under the curve [AUC], 0.815 [0.031]) and calibration (mean [SE] integrated calibration index, 0.040 [0.002]; mean [SE] expected calibration error, 0.039 [0.002]) in an independent test sample (patients from the South). Patients in the top 30% of predicted risk accounted for 65% of all 3-month PTSD or MDE, with a mean (SE) positive predictive value of 58.2% (6.4%) among these patients at high risk. The model had good consistency across regions of the country in terms of both AUC (mean [SE], 0.789 [0.025] using the Northeast as the test sample and 0.809 [0.023] using the Midwest as the test sample) and calibration (mean [SE] integrated calibration index, 0.048 [0.003] using the Northeast as the test sample and 0.024 [0.001] using the Midwest as the test sample; mean [SE] expected calibration error, 0.034 [0.003] using the Northeast as the test sample and 0.025 [0.001] using the Midwest as the test sample). The most important predictors in terms of Shapley Additive Explanations values were symptoms of anxiety sensitivity and depressive disposition, psychological distress in the 30 days before motor vehicle collision, and peritraumatic psychosomatic symptoms. Conclusions and relevance: The results of this study suggest that a short set of questions feasible to administer in an ED can predict 3-month PTSD or MDE with good AUC, calibration, and geographic consistency. Patients at high risk can be identified in the ED for targeting if cost-effective preventive interventions are developed.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 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 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.