Racial Discrimination, Neural Connectivity, and Epigenetic Aging Among Black Women.

Importance: Racial discrimination increases the risk of adverse brain health outcomes, potentially via neuroplastic changes in emotion processing networks. The involvement of deep brain regions (brainstem and midbrain) in these responses is unknown. Potential associations of racial discrimination with alterations in deep brain functional connectivity and accelerated epigenetic aging, a process that substantially increases vulnerability to health problems, are also unknown. Objective: To examine associations of racial discrimination with brainstem and midbrain resting-state functional connectivity (RSFC) and DNA methylation age acceleration (DMAA) among Black women in the US. Design, Setting, and Participants: This cohort study was conducted between January 1, 2012, and February 28, 2015, and included a community-based sample of Black women (aged ≥18 years) recruited as part of the Grady Trauma Project. Self-reported racial discrimination was examined in association with seed-to-voxel brain connectivity, including the locus coeruleus (LC), periaqueductal gray (PAG), and superior colliculus (SC); an index of DMAA (Horvath clock) was also evaluated. Posttraumatic stress disorder (PTSD), trauma exposure, and age were used as covariates in statistical models to isolate racial discrimination-related variance. Data analysis was conducted between January 10 and October 30, 2023. Exposure: Varying levels of racial discrimination exposure, other trauma exposure, and posttraumatic stress disorder (PTSD). Main Outcomes and Measures: Racial discrimination frequency was assessed with the Experiences of Discrimination Scale, other trauma exposure was evaluated with the Traumatic Events Inventory, and current PTSD was evaluated with the PTSD Symptom Scale. Seed-to-voxel functional connectivity analyses were conducted with LC, PAG, and SC seeds. To assess DMAA, the Methylation EPIC BeadChip assay (Illumina) was conducted with whole-blood samples from a subset of 49 participants. Results: This study included 90 Black women, with a mean (SD) age of 38.5 (11.3) years. Greater racial discrimination was associated with greater left LC RSFC to the bilateral precuneus (a region within the default mode network implicated in rumination and reliving of past events; cluster size k = 228; t85 = 4.78; P < .001, false discovery rate-corrected). Significant indirect effects were observed for the left LC-precuneus RSFC on the association between racial discrimination and DMAA (ß [SE] = 0.45 [0.16]; 95% CI, 0.12-0.77). Conclusions and Relevance: In this study, more frequent racial discrimination was associated with proportionately greater RSFC of the LC to the precuneus, and these connectivity alterations were associated with DMAA. These findings suggest that racial discrimination contributes to accelerated biological aging via altered connectivity between the LC and default mode network, increasing vulnerability for brain health problems.

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.

Functional Domains of Substance Use and their Implications to Trauma: A Systematic Review of Neuroimaging Studies.

Substance use disorder (SUD) is a significant health problem, and trauma exposure is a known risk factor for the escalation of substance use. However, the shared neural mechanisms through which trauma is associated with substance use are still unknown. Therefore, we systematically review neuroimaging studies focusing on three domains that may contribute to the overlapping mechanisms of SUD and trauma-reward salience, negative emotionality, and inhibition. Using PRISMA guidelines, we identified 45 studies utilizing tasks measuring these domains in alcohol, tobacco, and cannabis use groups. Greater reward, lesser regulation of inhibitory processes, and mixed findings of negative emotionality processes in individuals who use substances versus controls were found. Specifically, greater orbitofrontal cortex, ventral tegmental area, striatum, amygdala, and hippocampal activation was found in response to reward-related tasks, and reduced activation was found in the inferior frontal gyrus and hippocampus in response to inhibition-related tasks. Importantly, no studies in trauma-exposed individuals met our review criteria. Future studies examining the role of trauma-related factors are needed, and more studies should explore inhibition- and negative-emotionality domains in individuals who use substances to uncover clinically significant alterations in these domains that place an individual at greater risk for developing a SUD.

Accuracy of MRI-ultrasound fusion-guided and systematic biopsy of the prostate.

OBJECTIVES: Prostate multiparametric MRI (mpMRI) with subsequent targeted biopsy of suspicious lesions has a critical role in the diagnostic workup of prostate cancer. The objective was to evaluate the diagnostic accuracy of systematic biopsies, targeted biopsies, and the combination of both in prostate cancer detection. METHODS: From January 1, 2013 to June 1, 2022, biopsy-naïve and prior biopsy-negative patients who underwent both systematic and targeted biopsies were included. MRIs were evaluated according to PI-RADS with biopsy threshold set at PI-RADS ≥3. Systematic biopsies consisted of 8-12 cores, based on prostate volume. Overall prostate cancer and clinically significant cancer (Gleason Score ≥3 + 4) detection rates were stratified based on PI-RADS and location within the prostate, and compared between biopsy types using McNemar test. RESULTS: Among 867 patients, 615 had prostate cancer, with 434 clinically significant cases. Overall detection rates were: PI-RADS 3 48%, PI-RADS 4 72%, and PI-RADS 5 90%. Detection rates for clinically significant cancer were 21%, 53%, and 72%, respectively. The combination of biopsy methods was most accurate in detecting clinically significant prostate cancer (P < .001). Targeted biopsies alone detected more clinically significant prostate cancer than systematic biopsies alone (43.1% vs 40.3%, P = .046). For posterior PI-RADS 5 lesions, no statistically significant difference was found between all biopsy methods. CONCLUSIONS: In the detection of clinically significant prostate cancer, the combination of systematic and targeted biopsies proves most effective. Targeted biopsies rarely missed significant cancer for posterior PI-RADS 5 lesions, suggesting systematic biopsies could be reserved for instances where targeted biopsy results are negative. ADVANCES IN KNOWLEDGE: This study emphasizes on the efficacy of mpMRI and targeted biopsies in suspected prostate cancer in real-world clinical context. For PI-RADS 5 lesions, systematic biopsies provide limited clinical benefit and may only be necessary when targeted biopsy results are negative.

HIV Interacts with Posttraumatic Stress Disorder to Impact Fear Psychophysiology in Trauma-Exposed Black Women.

Background: The prevalence of posttraumatic stress disorder (PTSD) among people living with HIV (PLWH) is higher than in the general population and can impact health behaviors. The influence of HIV on PTSD psychophysiology requires further investigation due to implications for the treatment of PTSD in PLWH. Objective: Utilizing fear-potentiated startle (FPS), we aimed to interrogate the influence of PTSD and HIV on fear responses. Materials and Methods: Women (18-65 years of age) recruited from the Women's Interagency HIV Study in Atlanta, GA (n = 70, 26 without HIV and 44 with HIV), provided informed consent and completed a semistructured interview to assess trauma exposure and PTSD symptom severity. Participants also underwent an FPS paradigm to assess fear acquisition and extinction: Psychophysiological indices that measure how individuals learn new fear and then subsequently attempt to suppress this fear. Results: Women with PTSD, who did not have HIV, exhibited a greater startle response compared to women without PTSD or HIV during late acquisition to both the danger cue, reinforced conditioned stimulus (CS+, p = 0.013)), and the safety cue, non-reinforced conditioned stimulus (CS-, p = 0.046)), whereas women living with HIV (WLH) and PTSD demonstrated blunted fear responses compared to women with PTSD only. During extinction, WLH comorbid with PTSD exhibited an increased fear response during the extinction period in comparison to all other groups (p = 0.023). Women without PTSD demonstrated a reduction in the fear response during extinction regardless of HIV status. Conclusion: Our findings indicate that HIV further modifies fear psychophysiology in WLH with comorbid PTSD, highlighting the importance of considering HIV status in conjunction with PTSD treatment.

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.

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup.

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

Feasibility of tracking invasive Escherichia coli disease among older adults in a community setting: A prospective observational study.

PURPOSE: Invasive Escherichia coli disease (IED) encompasses a diverse range of sterile site infections. This study evaluated the feasibility of capturing IED among community-dwelling older adults to inform the implementation of a phase 3 efficacy trial of a novel vaccine against IED (NCT04899336). METHODS: EXPECT-1 (NCT04087681) was a prospective, multinational, observational study conducted in medically stable participants aged ≥ 60 years. At least 50% of participants were selected based on a history of urinary tract infection (UTI) in the previous 10 years. The main outcomes were the incidence of IED and the number of hospitalisations reported by the site vs participant. The length of follow-up was 12 months. In a US-based substudy, a smartphone-based geofencing was evaluated to track hospital entries. RESULTS: In total, 4470 participants were enrolled (median age, 70.0 years); 59.5% (2657/4469) of participants had a history of UTI in the previous 10 years. Four IED events were captured through deployment of different tracking methods: a self-report, a general practitioner (GP) report, and a follow-up call. The incidence rate of IED was 98.6 events per 100,000 person-years. The number of reported hospitalisations was 2529/4470 (56.6%) by the site and 2177/4470 (48.7%) by participants; 13.8% of hospitalisations would have been missed if utilising only site reports. Geofencing detected 72 hospital entries. CONCLUSION: Deployment of multiple tracking methods can optimise detection of IED among community-dwelling older adults. Older adults with a history of UTI could be feasibly targeted for a phase 3 vaccine efficacy trial through a network of GPs.

Clinical presentation and antimicrobial resistance of invasive Escherichia coli disease in hospitalized older adults: a prospective multinational observational study.

BACKGROUND: Clinical data characterizing invasive Escherichia coli disease (IED) are limited. We assessed the clinical presentation of IED and antimicrobial resistance (AMR) patterns of causative E. coli isolates in older adults. METHODS: EXPECT-2 (NCT04117113) was a prospective, observational, multinational, hospital-based study conducted in patients with IED aged ≥ 60 years. IED was determined by the microbiological confirmation of E. coli from blood; or by the microbiological confirmation of E. coli from urine or an otherwise sterile body site in the presence of requisite criteria of systemic inflammatory response syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), or quick SOFA (qSOFA). The primary outcomes were the clinical presentation of IED and AMR rates of E. coli isolates to clinically relevant antibiotics. Complications and in-hospital mortality were assessed through 28 days following IED diagnosis. RESULTS: Of 240 enrolled patients, 80.4% had bacteremic and 19.6% had non-bacteremic IED. One-half of infections (50.4%) were community-acquired. The most common source of infection was the urinary tract (62.9%). Of 240 patients, 65.8% fulfilled ≥ 2 SIRS criteria, and 60.4% had a total SOFA score of ≥ 2. Investigator-diagnosed sepsis and septic shock were reported in 72.1% and 10.0% of patients, respectively. The most common complication was kidney dysfunction (12.9%). The overall in-hospital mortality was 4.6%. Of 299 E. coli isolates tested, the resistance rates were: 30.4% for trimethoprim-sulfamethoxazole, 24.1% for ciprofloxacin, 22.1% for levofloxacin, 16.4% for ceftriaxone, 5.7% for cefepime, and 4.3% for ceftazidime. CONCLUSIONS: The clinical profile of identified IED cases was characterized by high rates of sepsis. IED was associated with high rates of AMR to clinically relevant antibiotics. The identification of IED can be optimized by using a combination of clinical criteria (SIRS, SOFA, or qSOFA) and culture results.

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.

Accelerated TMS - moving quickly into the future of depression treatment.

Accelerated TMS is an emerging application of Transcranial Magnetic Stimulation (TMS) aimed to reduce treatment length and improve response time. Extant literature generally shows similar efficacy and safety profiles compared to the FDA-cleared protocols for TMS to treat major depressive disorder (MDD), yet accelerated TMS research remains at a very early stage in development. The few applied protocols have not been standardized and vary significantly across a set of core elements. In this review, we consider nine elements that include treatment parameters (i.e., frequency and inter-stimulation interval), cumulative exposure (i.e., number of treatment days, sessions per day, and pulses per session), individualized parameters (i.e., treatment target and dose), and brain state (i.e., context and concurrent treatments). Precisely which of these elements is critical and what parameters are most optimal for the treatment of MDD remains unclear. Other important considerations for accelerated TMS include durability of effect, safety profiles as doses increase over time, the possibility and advantage of individualized functional neuronavigation, use of biological readouts, and accessibility for patients most in need of the treatment. Overall, accelerated TMS appears to hold promise to reduce treatment time and achieve rapid reduction in depressive symptoms, but at this time significant work remains to be done. Rigorous clinical trials combining clinical outcomes and neuroscientific measures such as electroencephalogram, magnetic resonance imaging and e-field modeling are needed to define the future of accelerated TMS for MDD.

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.

Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure.

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.

Structural inequities contribute to racial/ethnic differences in neurophysiological tone, but not threat reactivity, after trauma exposure.

Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.

Amygdala responses to threat in violence-exposed children depend on trauma context and maternal caregiving.

Early life adversity (ELA) has been linked with increased arousal responses to threat, including increased amygdala reactivity. Effects of ELA on brain function are well recognized, and emerging evidence suggests that caregivers may influence how environmental stressors impact children's brain function. We investigated the hypothesis that positive interaction between mother and child can buffer against ELA effects on children's neural responses to threat, and related symptoms. N = 53 mother-child pairs (children ages 8-14 years) were recruited from an urban population at high risk for violence exposure. Maternal caregiving was measured using the Parenting Questionnaire and in a cooperation challenge task. Children viewed fearful and neutral face stimuli during functional magnetic resonance imaging. Children who experienced greater violence at home showed amygdala sensitization, whereas children experiencing more school and community violence showed amygdala habituation. Sensitization was in turn linked with externalizing symptoms. However, maternal warmth was associated with a normalization of amygdala sensitization in children, and fewer externalizing behaviors prospectively up to 1 year later. Findings suggested that the effects of violence exposure on threat-related neural circuitry depend on trauma context (inside or outside the home) and that primary caregivers can increase resilience.

Harmonizing PTSD severity scales across instruments and sites.

OBJECTIVE: The variety of instruments used to assess posttraumatic stress disorder (PTSD) allows for flexibility, but also creates challenges for data synthesis. The objective of this work was to use a multisite mega analysis to derive quantitative recommendations for equating scores across measures of PTSD severity. METHOD: Empirical Bayes harmonization and linear models were used to describe and mitigate site and covariate effects. Quadratic models for converting scores across PTSD assessments were constructed using bootstrapping and tested on hold out data. RESULTS: We aggregated 17 data sources and compiled an n = 5,634 sample of individuals who were assessed for PTSD symptoms. We confirmed our hypothesis that harmonization and covariate adjustments would significantly improve inference of scores across instruments. Harmonization significantly reduced cross-dataset variance (28%, p < .001), and models for converting scores across instruments were well fit (median R² = 0.985) with an average root mean squared error of 1.46 on sum scores. CONCLUSIONS: These methods allow PTSD symptom severity to be placed on multiple scales and offers interesting empirical perspectives on the role of harmonization in the behavioral sciences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).