Reward neurocircuitry predicts longitudinal changes in alcohol use following trauma exposure.

BACKGROUND: Trauma is a risk factor for developing maladaptive alcohol use. Preclinical research has shown that stress alters the processing of midbrain and striatal reward and incentive signals. However, little research has been conducted on alterations in reward-related neurocircuitry post-trauma in humans. Neuroimaging markers may be particularly useful as they can provide insight into the mechanisms that may make an individual vulnerable to developing trauma-related psychopathologies. This study aimed to identify reward-related neural correlates associated with changes in alcohol use after trauma exposure. METHODS: Participants were recruited from U.S. emergency departments for the AURORA study (N=286, 178 female). Trauma-related change in alcohol use at 8 weeks post-trauma relative to pre-trauma was quantified as a change in 30-day total drinking per the PhenX Toolkit Alcohol 30-Day Quantity and Frequency Measure. Reward-related neurocircuitry activation and functional connectivity (FC) were assessed 2 weeks post-trauma using fMRI during a monetary reward task using region of interest and whole-brain voxelwise analyses. RESULTS: Greater increase in alcohol use from pre-trauma to 8 weeks post-trauma was predicted by (1) greater ventral tegmental area (VTA) and (2) greater cerebellum activation during Gain>Loss trials measured 2 weeks post-trauma and (3) greater seed-based FC between the VTA and lateral occipital cortex and precuneus. CONCLUSIONS: Altered VTA activation and FC early post-trauma may be associated with reward-seeking and processing, contributing to greater alcohol use post-trauma. These data provide novel evidence of neural correlates that underlie increased alcohol use early post-trauma that may be targeted via early interventions to prevent the development of maladaptive alcohol use.

Emergency Medicaid enrollment after traumatic injury predicts long-term health care utilization.

BACKGROUND: Injured patients have high rates of uninsurance, which is associated with worse outcomes. Insurance linkage programs that connect patients to Medicaid coverage can prevent catastrophic costs for patients. Less is known about the long-term impact of insurance enrollment. We examined health care utilization for previously uninsured patients, hypothesizing that newly insured patients postinjury would use health care more than those remaining uninsured. METHODS: We linked institutional trauma registry data to the electronic medical record to identify injured patients aged 18 to 64 years from 2017 to 2021. Patients admitted without insurance and then retroactively insured (RI) during hospitalization were compared with patients with preestablished Medicaid (Medicaid insured [MI]) and those remaining uninsured. We compared demographic and injury characteristics and future health care utilization, including hospitalizations, emergency department (ED) visits, and clinic visits, among groups at 30 days and 12 months postinjury. Patient-reported outcomes (PROs) 6 months after injury were compared by group for a subset of patients participating in an ongoing study of long-term PROs. RESULTS: We compared 494 RI patients with 1,706 MI and 148 uninsured patients. Retroactively insured patients were younger, more likely to have penetrating injuries, and longer hospitalization than other groups. There was a significant increase in ED and clinic visits and hospital admissions at 30 days and 12 months between RI and uninsured patients (p < 0.001). Using multivariable logistic regression, RI was associated with higher future ED utilization, hospital admissions, and specialist visits at 30 days and 12 months compared with uninsured patients. Of the 265 patients with 6-month PROs, Medicaid coverage was not associated with any significant difference in physical function or anxiety. CONCLUSION: Patients enrolled in insurance postinjury are more likely to use health care in the future than patients without insurance, but the downstream effects are less clear. Health insurance is a necessary step but not independently sufficient to optimize care and improve health outcomes. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Fatal and Nonfatal Firearm Injury Rates by Race and Ethnicity in the United States, 2019 to 2020.

BACKGROUND: Racial disparities in firearm injury death in the United States are well established. Less is known about the magnitude of nonfatal and total firearm injury. OBJECTIVE: To combine health care data with death certificate data to estimate total firearm injuries in various racial and ethnic groups. DESIGN: Retrospective, cross-sectional study. SETTING: Fatal injury data were collected from the Centers for Disease Control and Prevention. Data on nonfatal injuries were collected from the Nationwide Emergency Department Sample (NEDS), a 20% stratified sample of U.S. emergency department visits, weighted to provide national estimates for the United States, 2019 to 2020. PARTICIPANTS: All firearm injuries and deaths in the United States. INTERVENTION: Race and ethnicity were classified into 5 mutually exclusive categories: Asian or Pacific Islander, Black, Hispanic, Native American, and White. International Classification of Diseases, 10th Revision codes were used to classify firearm injury intent. MEASUREMENTS: Incidence of fatal and nonfatal injury in the U.S. population and case-fatality ratios (CFRs). RESULTS: There were 252 376 total firearm injuries, including 84 908 deaths from firearm injures. Of all firearm injuries, 37.8% were unintentional, 37.3% were assault related, 21.0% were self-harm, and 1.3% were law enforcement associated. Self-harm had the highest CFRs (90.9% overall). Unintentional injuries accounted for just 1021 (1.2%) deaths but 94 433 (56.4%) of nonfatal injuries. Rates of self-harm were highest among White persons (11.0 per 100 000 population in 2020) followed by Native Americans (8.6 per 100 000). Rates of assault were highest among Black persons (70.1 per 100 000), as were unintentional injuries (56.1 per 100 000). LIMITATION: Findings are limited by the accuracy of discharge coding in NEDS, particularly regarding injury intent and patient race and ethnicity. CONCLUSION: From 2019 to 2020, the total burden of firearm injuries amounts to an average of 1 injury every 4 minutes and 1 death every 12 minutes in the United States. Racial disparities in firearm injury death are mirrored in nonfatal injury. PRIMARY FUNDING SOURCE: None.

Neighborhood Resources Associated With Psychological Trajectories and Neural Reactivity to Reward After Trauma.

Importance: Research on resilience after trauma has often focused on individual-level factors (eg, ability to cope with adversity) and overlooked influential neighborhood-level factors that may help mitigate the development of posttraumatic stress disorder (PTSD). Objective: To investigate whether an interaction between residential greenspace and self-reported individual resources was associated with a resilient PTSD trajectory (ie, low/no symptoms) and to test if the association between greenspace and PTSD trajectory was mediated by neural reactivity to reward. Design, Setting, and Participants: As part of a longitudinal cohort study, trauma survivors were recruited from emergency departments across the US. Two weeks after trauma, a subset of participants underwent functional magnetic resonance imaging during a monetary reward task. Study data were analyzed from January to November 2023. Exposures: Residential greenspace within a 100-m buffer of each participant's home address was derived from satellite imagery and quantified using the Normalized Difference Vegetation Index and perceived individual resources measured by the Connor-Davidson Resilience Scale (CD-RISC). Main Outcome and Measures: PTSD symptom severity measured at 2 weeks, 8 weeks, 3 months, and 6 months after trauma. Neural responses to monetary reward in reward-related regions (ie, amygdala, nucleus accumbens, orbitofrontal cortex) was a secondary outcome. Covariates included both geocoded (eg, area deprivation index) and self-reported characteristics (eg, childhood maltreatment, income). Results: In 2597 trauma survivors (mean [SD] age, 36.5 [13.4] years; 1637 female [63%]; 1304 non-Hispanic Black [50.2%], 289 Hispanic [11.1%], 901 non-Hispanic White [34.7%], 93 non-Hispanic other race [3.6%], and 10 missing/unreported [0.4%]), 6 PTSD trajectories (resilient, nonremitting high, nonremitting moderate, slow recovery, rapid recovery, delayed) were identified through latent-class mixed-effect modeling. Multinominal logistic regressions revealed that for individuals with higher CD-RISC scores, greenspace was associated with a greater likelihood of assignment in a resilient trajectory compared with nonremitting high (Wald z test = -3.92; P < .001), nonremitting moderate (Wald z test = -2.24; P = .03), or slow recovery (Wald z test = -2.27; P = .02) classes. Greenspace was also associated with greater neural reactivity to reward in the amygdala (n = 288; t277 = 2.83; adjusted P value = 0.02); however, reward reactivity did not differ by PTSD trajectory. Conclusions and Relevance: In this cohort study, greenspace and self-reported individual resources were significantly associated with PTSD trajectories. These findings suggest that factors at multiple ecological levels may contribute to the likelihood of resiliency to PTSD after trauma.

Probing the neurocardiac circuit in trauma and posttraumatic stress.

The neurocardiac circuit is integral to physiological regulation of threat and trauma-related responses. However, few direct investigations of brain-behavior associations with replicable physiological markers of PTSD have been conducted. The current study probed the neurocardiac circuit by examining associations among its core regions in the brain (e.g., insula, hypothalamus) and the periphery (heart rate [HR], high frequency heart rate variability [HF-HRV], and blood pressure [BP]). We sought to characterize these associations and to determine whether there were differences by PTSD status. Participants were N = 315 (64.1 % female) trauma-exposed adults enrolled from emergency departments as part of the prospective AURORA study. Participants completed a deep phenotyping session (e.g., fear conditioning, magnetic resonance imaging) two weeks after emergency department admission. Voxelwise analyses revealed several significant interactions between PTSD severity 8-weeks posttrauma and psychophysiological recordings on hypothalamic connectivity to the prefrontal cortex (PFC), insula, superior temporal sulcus, and temporoparietaloccipital junction. Among those with PTSD, diastolic BP was directly correlated with right insula-hypothalamic connectivity, whereas the reverse was found for those without PTSD. PTSD status moderated the association between systolic BP, HR, and HF-HRV and hypothalamic connectivity in the same direction. While preliminary, our findings may suggest that individuals with higher PTSD severity exhibit compensatory neural mechanisms to down-regulate autonomic imbalance. Additional study is warranted to determine how underlying mechanisms (e.g., inflammation) may disrupt the neurocardiac circuit and increase cardiometabolic disease risk in PTSD.

Nearly 20 Years Since the Federal Ban: Can State-Level Assault Weapon Prohibitions Fill the Void? Comparative Analysis of Case Fatality and Assault Weapon Recovery in States With and Without an Assault Weapon Ban.

INTRODUCTION: Few states established assault weapon bans (AWBs) after the federal AWB expired. The effectiveness of state AWBs as well as neighboring state legislation, in reducing the local prevalence of assault weapons (AWs) or in reducing overall shooting lethality is unknown. METHODS: We queried the Gun Violence Archive (2014-2021) to identify US firearm injuries and fatalities. Shooting case fatality rates were compared among states with and without AWBs, as reported in the State Firearm Laws Database. Data on recovered firearms was obtained from the ATF Firearms Trace Database and used to estimate weapon prevalence. Recovered firearms were classified as AWs based on caliber (7.62 mm, 5.56 mm, 0.223 cal). We performed spatially weighted linear regression models, with fixed effects for state and year to assess the association between geographically clustered state legislation and firearm outcomes. RESULTS: From 2014 to 2021, the US shooting victim case fatality rate was 8.06% and did not differ among states with and without AWBs. The proportion of AWs to total firearms was 5.0% in states without an AWB and 6.0% in states with an AWB (mean difference [95% CI] = -0.8% [-1.6% to -0.2%], P = 0.03). Most recovered firearms in AWB states originated from non-AWB states. On adjusted models, there was no association between state-level AWB and firearm case fatality; however, adjacency to states with an AWB was associated with lower case fatality (P < 0.001). Clustered AWB states with shared borders had lower AW prevalence and fatality rates than the rest of the US. CONCLUSIONS: Isolated state AWBs are not inversely associated with shooting case fatality rates nor the prevalence of AWs, but AWBs among multiple neighboring states may be associated with both outcomes.

Intensive longitudinal assessment following index trauma to predict development of PTSD using machine learning.

There are significant challenges to identifying which individuals require intervention following exposure to trauma, and a need for strategies to identify and provide individuals at risk for developing PTSD with timely interventions. The present study seeks to identify a minimal set of trauma-related symptoms, assessed during the weeks following traumatic exposure, that can accurately predict PTSD. Participants were 2185 adults (Mean age=36.4 years; 64% women; 50% Black) presenting for emergency care following traumatic exposure. Participants received a 'flash survey' with 6-8 varying symptoms (from a pool of 26 trauma symptoms) several times per week for eight weeks following the trauma exposure (each symptom assessed ∼6 times). Features (mean, sd, last, worst, peak-end scores) from the repeatedly assessed symptoms were included as candidate variables in a CART machine learning analysis to develop a pragmatic predictive algorithm. PTSD (PCL-5 ≥38) was present for 669 (31%) participants at the 8-week follow-up. A classification tree with three splits, based on mean scores of nervousness, rehashing, and fatigue, predicted PTSD with an Area Under the Curve of 0.836. Findings suggest feasibility for a 3-item assessment protocol, delivered once per week, following traumatic exposure to assess and potentially facilitate follow-up care for those at risk.

Thoracic irrigation for prevention of secondary intervention after thoracostomy tube drainage for hemothorax: A Western Trauma Association multi-center study.

BACKGROUND: Retained hemothorax (rHTX) requiring intervention occurs in up to 20% of patients who undergo chest tube (TT) placement for a hemothorax (HTX). Thoracic irrigation at the time of TT placement decreases the need for secondary intervention in this patient group but those findings are limited because of the single center design. A multi-center study was conducted to evaluate the effectiveness of thoracic irrigation. METHODS: A multi-center, prospective, observational study was conducted between June 2018 and July 2023. Eleven sites contributed patients. Patients were included if they had a TT placed for a HTX and were excluded if: age < 18 years, TT for pneumothorax, thoracotomy or VATS performed within 6 hours of TT, TT >24 hours after injury, TT removed <24 hours, or death within 48 hours. Thoracic irrigation was performed at the discretion of the attending. Each hemithorax was considered separately if bilateral HTX. The primary outcome was secondary intervention for HTX-related complications (rHTX, effusion, or empyema). Secondary intervention was defined as: TT placement, instillation of thrombolytics, VATS, or thoracotomy. Irrigated and non-irrigated hemithoraces were compared using a propensity weighted analysis with age, sex, mechanism of injury, Abbreviated Injury Scale (AIS) chest and TT size as predictors. RESULTS: 493 patients with 462 treated hemothoraces were included, 123 (25%) had thoracic irrigation at TT placement. There were no significant demographic differences between the cohorts. Fifty-seven secondary interventions were performed, 10 (8%) and 47 (13%) in the irrigated and non-irrigated groups, respectively (p = 0.015). Propensity weighted analysis demonstrated a reduction in secondary interventions in the irrigated cohort (Odds Ratio 0.56 (0.34-0.85); p = 0.005). CONCLUSION: This Western Trauma Association multi-center study demonstrates a benefit of thoracic irrigation at the time of TT placement for a HTX. Thoracic irrigation reduces the odds of a secondary intervention for rHTX-related complications by 44%. LEVEL OF EVIDENCE: Therapeutic Study, Level II.

Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study.

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD. METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men. RESULTS: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects. CONCLUSIONS: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Hemodynamic Deterioration of Trauma Patients Undergoing Interhospital Transfer.

INTRODUCTION: Organized trauma systems reduce morbidity and mortality after serious injury. Rapid transport to high-level trauma centers is ideal, but not always feasible. Thus, interhospital transfers are an important component of trauma systems. However, transferring a seriously injured patient carries the risk of worsening condition before reaching definitive care. In this study, we evaluated characteristics and outcomes of patients whose hemodynamic status worsened during the transfer process. METHODS: We conducted a retrospective cohort study using data from the Pennsylvania Trauma Outcomes Study database from 2011 to 2018. Patients were included if they had a heart rate ≤ 100 and systolic blood pressure ≥ 100 at presentation to the referring hospital and were transferred within 24 h. We defined hemodynamic deterioration (HDD) as admitting heart rate > 100 or systolic blood pressure < 100 at the receiving center. We compared demographics, mechanism of injury, injury severity, management, and outcomes between patients with and without HDD using descriptive statistics and multivariable regression analysis. RESULTS: Of 52,919 included patients, 5331 (10.1%) had HDD. HDD patients were more often moderately-severely injured (injury severity score 9-15; 40.4% versus 39.4%, P < 0.001) and injured via motor vehicle collision (23.2% versus 16.6%, P < 0.001) or gunshot wound (2.1% versus 1.3%, P < 0.001). HDD patients more often had extremity or torso injuries and after transfer were more likely to be transferred to the intensive care unit (35% versus 28.5%, P < 0.001), go directly to surgery (8.4% versus 5.9%, P < 0.001), or interventional radiology (0.8% versus 0.3%, P < 0.001). Overall mortality in the HDD group was 4.9% versus 2.1% in the group who remained stable. These results were confirmed using multivariable analysis. CONCLUSIONS: Interhospital transfers are essential in trauma, but one in 10 transferred patients deteriorated hemodynamically in that process. This high-risk component of the trauma system requires close attention to the important aspects of transfer such as patient selection, pretransfer management/stabilization, and communication between facilities.

Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk.

Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD. Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables. Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated. Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata.

Brain dynamics reflecting an intra-network brain state is associated with increased posttraumatic stress symptoms in the early aftermath of trauma.

This 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.

Sex Differences in Response Inhibition-Related Neural Predictors of Posttraumatic Stress Disorder in Civilians With Recent Trauma.

BACKGROUND: Females are more likely to develop posttraumatic stress disorder (PTSD) than males. Impaired inhibition has been identified as a mechanism for PTSD development, but studies on potential sex differences in this neurobiological mechanism and how it relates to PTSD severity and progression are relatively rare. Here, we examined sex differences in neural activation during response inhibition and PTSD following recent trauma. METHODS: Participants (n = 205, 138 female sex assigned at birth) were recruited from emergency departments within 72 hours of a traumatic event. PTSD symptoms were assessed 2 weeks and 6 months posttrauma. A Go/NoGo task was performed 2 weeks posttrauma in a 3T magnetic resonance imaging scanner to measure neural activity during response inhibition in the ventromedial prefrontal cortex, right inferior frontal gyrus, and bilateral hippocampus. General linear models were used to examine the interaction effect of sex on the relationship between our regions of interest and the whole brain, PTSD symptoms at 6 months, and symptom progression between 2 weeks and 6 months. RESULTS: Lower response inhibition-related ventromedial prefrontal cortex activation 2 weeks posttrauma predicted more PTSD symptoms at 6 months in females but not in males, while greater response inhibition-related right inferior frontal gyrus activation predicted lower PTSD symptom progression in males but not females. Whole-brain interaction effects were observed in the medial temporal gyrus and left precentral gyrus. CONCLUSIONS: There are sex differences in the relationship between inhibition-related brain activation and PTSD symptom severity and progression. These findings suggest that sex differences should be assessed in future PTSD studies and reveal potential targets for sex-specific interventions.

The role of emergency department thoracotomy in patients with cranial gunshot wounds.

BACKGROUND: Although several society guidelines exist regarding emergency department thoracotomy (EDT), there is a lack of data upon which to base guidance for multiple gunshot wound (GSW) patients whose injuries include a cranial GSW. We hypothesized that survival in these patients would be exceedingly low. METHODS: We used Pennsylvania Trauma Outcomes Study data, 2002 to 2021, and included EDTs for GSWs. We defined EDT by International Classification of Diseases codes for thoracotomy or procedures requiring one, with a location flagged as emergency department. We defined head injuries as any head Abbreviated Injury Scale (AIS) score of ≥1 and severe head injuries as head AIS score of ≥4. Head injuries were "isolated" if all other body regions have an AIS score of <2. Descriptive statistics were performed. Discharge functional status was measured in five domains. RESULTS: Over 20 years in Pennsylvania, 3,546 EDTs were performed; 2,771 (78.1%) were for penetrating injuries. Most penetrating EDTs (2,003 [72.3%]) had suffered GSWs. Survival among patients with isolated head wounds (n = 25) was 0%. Survival was 5.3% for the non-head injured (n = 94 of 1,787). In patients with combined head and other injuries, survival was driven by the severity of the head wound-0% (0 of 81) with a severe head injury ( p = 0.035 vs. no severe head injury) and 4.5% (5 of 110) with a nonsevere head injury. Of the five head-injured survivors, two were fully dependent for transfer mobility, and three were partially or fully dependent for locomotion. Of 211 patients with a cranial injury who expired, 2 (0.9%) went on to organ donation. CONCLUSION: Although there is clearly no role for EDT in patients with isolated head GSWs, EDT may be considered in patients with combined injuries, as most of these patients have minor head injuries and survival is not different from the non-head injured. However, if a severe head injury is clinically apparent, even in the presence of other body cavity injuries, EDT should not be pursued. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals.

BACKGROUND: 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.

Colleges and Crime-Comparing Homicide and Suicide Rates Among College Towns and Their Counterparts.

INTRODUCTION: To investigate differences in homicide and suicide rates across college town status and determine whether college towns were predisposed to changes in rates over time. METHODS: We analyzed county-level homicide and suicide rates (total and by firearm) across college town status using 2015-2019 CDC death certificate data and data from the American Communities Project. RESULTS: Population-level homicide rates were similar across college town status, but younger age groups were at increased risk for firearm homicide and total homicide in college towns. College town status was associated with lower population-level firearm suicide rates, but individuals aged less than 18 y were at increased risk for total and firearm suicide. Finally, college towns were not classified as outliers for changes in either firearm homicide or suicide rates over time. CONCLUSIONS: College towns had similar homicide rates and significantly lower firearm suicide rates than other counties; however, individuals aged less than 18 y were at increased risk for both outcomes. The distinctive demographic, social, economic, and cultural features of college towns may contribute to differing risk profiles among certain age groups, thus may also be amenable to focused prevention efforts.

Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure.

Patients 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.

Prior Sexual Trauma Exposure Impacts Posttraumatic Dysfunction and Neural Circuitry Following a Recent Traumatic Event in the AURORA Study.

Background: 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.

Neighborhood Disadvantage and Neural Correlates of Threat and Reward Processing in Survivors of Recent Trauma.

Importance: 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; ß = 0.20; corrected P = .008) and anterior cingulate cortex (ACC; t274 = 2.56; ß = 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; ß = 0.21; corrected P = .001) and gray matter morphology of the ACC (cortical thickness: t273 = -2.29; ß = -0.13; corrected P = .02; surface area: t273 = 2.53; ß = 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: ß = -0.17; standard error = 0.06, t= -2.28; P = .007; at 1 SD above the mean: ß = -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.