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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 Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure(Springer Nature, 2023-11-18) Zeamer, Abigail L.; Salive, Marie-Claire; An, Xinming; Beaudoin, Francesca L.; House, Stacey L.; Stevens, Jennifer S.; Zeng, Donglin; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Rauch, Scott L.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Swor, Robert A.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Harris, Erica; 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.; Kessler, Ronald C.; Koenen, Karestan C.; McLean, Samuel A.; Bucci, Vanni; Haran, John P.; Emergency Medicine, School of MedicinePatients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. We performed metagenomic analysis on stool samples (n = 51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA (AURORA) study. Two-, eight- and twelve-week post-trauma outcomes for post-traumatic stress disorder (PTSD) (PTSD checklist for DSM-5), normalized depression scores (PROMIS Depression Short Form 8b) and somatic symptom counts were collected. Generalized linear models were created for each outcome using microbial abundances and relevant demographics. Mixed-effect random forest machine learning models were used to identify associations between APNS outcomes and microbial features and encoded metabolic pathways from stool metagenomics. Microbial species, including Flavonifractor plautii, Ruminococcus gnavus and, Bifidobacterium species, which are prevalent commensal gut microbes, were found to be important in predicting worse APNS outcomes from microbial abundance data. Notably, through APNS outcome modeling using microbial metabolic pathways, worse APNS outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways. Common commensal microbial species are enriched in individuals who develop APNS. More notably, we identified a biological mechanism through which the gut microbiome reduces global arginine bioavailability, a metabolic change that has also been demonstrated in the plasma of patients with PTSD.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 dynamics reflecting an intra-network brain state is associated with increased posttraumatic stress symptoms in the early aftermath of trauma(Research Square, 2024-03-08) Sendi, Mohammad; Fu, Zening; Harnett, Nathaniel; van Rooij, Sanne; Vergara, Victor; Pizzagalli, Diego; Daskalakis, Nikolaos; House, Stacey; Beaudoin, Francesca; An, Xinming; Neylan, Thomas; Clifford, Gari; Jovanovic, Tanja; Linnstaedt, Sarah; Germine, Laura; Bollen, Kenneth; Rauch, Scott; Haran, John; Storrow, Alan; Lewandowski, Christopher; Musey, Paul, Jr.; Hendry, Phyllis; Sheikh, Sophia; Jones, Christopher; Punches, Brittany; Swor, Robert; Gentile, Nina; Murty, Vishnu; Hudak, Lauren; Pascual, Jose; Seamon, Mark; Harris, Erica; Chang, Anna; Pearson, Claire; Peak, David; Merchant, Roland; Domeier, Robert; Rathlev, Niels; O'Neil, Brian; Sergot, Paulina; Sanchez, Leon; Bruce, Steven; Sheridan, John; Harte, Steven; Kessler, Ronald; Koenen, Karestan; McLean, Samuel; Stevens, Jennifer; Calhoun, Vince; Ressler, Kerry; Emergency Medicine, School of MedicineThis study examines the association between brain dynamic functional network connectivity (dFNC) and current/future posttraumatic stress (PTS) symptom severity, and the impact of sex on this relationship. By analyzing 275 participants' dFNC data obtained ~2 weeks after trauma exposure, we noted that brain dynamics of an inter-network brain state link negatively with current (r=-0.179, pcorrected= 0.021) and future (r=-0.166, pcorrected= 0.029) PTS symptom severity. Also, dynamics of an intra-network brain state correlated with future symptom intensity (r = 0.192, pcorrected = 0.021). We additionally observed that the association between the network dynamics of the inter-network brain state with symptom severity is more pronounced in females (r=-0.244, pcorrected = 0.014). Our findings highlight a potential link between brain network dynamics in the aftermath of trauma with current and future PTSD outcomes, with a stronger protective effect of inter-network brain states against symptom severity in females, underscoring the importance of sex differences.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 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 Neighborhood Disadvantage and Neural Correlates of Threat and Reward Processing in Survivors of Recent Trauma(American Medical Association, 2023-09-05) Webb, E. Kate; Ely, Timothy D.; Rowland, Grace E.; 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.; 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.; Swor, Robert A.; Pascual, Jose L.; Seamon, Mark J.; Datner, Elizabeth M.; Pearson, Claire; Peak, David A.; Merchant, Roland C.; Domeier, Robert M.; Rathlev, Niels K.; Sergot, Paulina; Sanchez, Leon D.; Kessler, Ronald C.; Koenen, Karestan C.; McLean, Samuel A.; Stevens, Jennifer S.; Ressler, Kerry J.; Harnett, Nathaniel G.; Emergency Medicine, School of MedicineImportance: Differences in neighborhood socioeconomic characteristics are important considerations in understanding differences in risk vs resilience in mental health. Neighborhood disadvantage is associated with alterations in the function and structure of threat neurocircuitry. Objective: To investigate associations of neighborhood disadvantage with white and gray matter and neural reactivity to positive and negative stimuli in the context of trauma exposure. Design, setting, and participants: In this cross-sectional study, survivors of trauma who completed sociodemographic and posttraumatic symptom assessments and neuroimaging were recruited as part of the Advancing Understanding of Recovery After Trauma (AURORA) study between September 2017 and June 2021. Data analysis was performed from October 25, 2022, to February 15, 2023. Exposure: Neighborhood disadvantage was measured with the Area Deprivation Index (ADI) for each participant home address. Main outcomes and measures: Participants completed separate threat and reward tasks during functional magnetic resonance imaging. Diffusion-weighted and high-resolution structural images were also collected. Linear models assessed the association of ADI with reactivity, microstructure, and macrostructure of a priori regions of interest after adjusting for income, lifetime trauma, sex at birth, and age. A moderated-mediation model tested whether ADI was associated with neural activity via microstructural changes and if this was modulated by PTSD symptoms. Results: A total of 280 participants (183 females [65.4%]; mean [SD] age, 35.39 [13.29] years) completed the threat task and 244 participants (156 females [63.9%]; mean [SD] age, 35.10 [13.26] years) completed the reward task. Higher ADI (per 1-unit increase) was associated with greater insula (t274 = 3.20; β = 0.20; corrected P = .008) and anterior cingulate cortex (ACC; t274 = 2.56; β = 0.16; corrected P = .04) threat-related activity after considering covariates, but ADI was not associated with reward reactivity. Greater disadvantage was also associated with altered microstructure of the cingulum bundle (t274 = 3.48; β = 0.21; corrected P = .001) and gray matter morphology of the ACC (cortical thickness: t273 = -2.29; β = -0.13; corrected P = .02; surface area: t273 = 2.53; β = 0.13; corrected P = .02). The moderated-mediation model revealed that ADI was associated with ACC threat reactivity via cingulum microstructural changes (index of moderated mediation = -0.02). However, this mediation was only present in individuals with greater PTSD symptom severity (at the mean: β = -0.17; standard error = 0.06, t= -2.28; P = .007; at 1 SD above the mean: β = -0.28; standard error = 0.08; t = -3.35; P < .001). Conclusions and relevance: In this study, neighborhood disadvantage was associated with neurobiology that supports threat processing, revealing associations of neighborhood disadvantage with neural susceptibility for PTSD and suggesting how altered structure-function associations may complicate symptoms. Future work should investigate specific components of neighborhood disadvantage that may be associated with these outcomes.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 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.