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.

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.

Impacts of early life adversity on the neurocircuitry of emotional memory in children.

Similar to adults with posttraumatic stress disorder, children with early life adversity show bias in memory for negative emotional stimuli. However, it is not well understood how childhood adversity impacts mechanisms underlying emotional memory. N = 56 children (8-14 years, 48% female) reported on adverse experiences including potentially traumatic events and underwent fMRI while attending to emotionally pleasant, neutral, or negative images. Post-scan, participants completed a cued recall test to assess memory for these images. Emotional difference-in-memory (DM) scores were computed by subtracting negative or positive from neutral recall performance. All children showed enhancing effects of emotion on recall, with no effect of trauma load. However, children with less trauma showed a larger emotional DM for both positive and negative stimuli when amygdala or anterior hippocampal activity was higher. In contrast, highly trauma-exposed children demonstrated a lower emotional DM with greater amygdala or hippocampal activity. This suggested that alternative neural mechanisms might support emotional enhancement of encoding in children with greater trauma load. Whole-brain analyses revealed that right fusiform activity during encoding positively correlated with both trauma load and successful later recall of positive images. Therefore, highly trauma-exposed children may use alternative, potentially adaptive neural pathways via the ventral visual stream to encode positive emotional events.

Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms.

Hippocampal 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 StatementAlterations 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.

Neurophysiological changes associated with vibroacoustically-augmented breath-focused mindfulness for dissociation: targeting interoception and attention.

BACKGROUND: Dissociative symptoms can emerge after trauma and interfere with attentional control and interoception; disruptions to these processes are barriers to mind-body interventions such as breath-focused mindfulness (BFM). To overcome these barriers, we tested the use of an exteroceptive augmentation to BFM, using vibrations equivalent to the amplitude of the auditory waveform of the actual breath, delivered via a wearable subwoofer in real time (VBFM). We tested whether this device enhanced interoceptive processes, attentional control and autonomic regulation in trauma-exposed women with dissociative symptoms. METHODS: 65 women, majority (82%) Black American, aged 18-65 completed self-report measures of interoception and 6 BFM sessions, during which electrocardiographic recordings were taken to derive high-frequency heart rate variability (HRV) estimates. A subset (n = 31) of participants completed functional MRI at pre- and post-intervention, during which they were administered an affective attentional control task. RESULTS: Compared to those who received BFM only, women who received VBFM demonstrated greater increases in interoception, particularly their ability to trust body signals, increased sustained attention, as well as increased connectivity between nodes of emotion processing and interoceptive networks. Intervention condition moderated the relationship between interoception change and dissociation change, as well as the relationship between dissociation and HRV change. CONCLUSIONS: Vibration feedback during breath focus yielded greater improvements in interoception, sustained attention and increased connectivity of emotion processing and interoceptive networks. Augmenting BFM with vibration appears to have considerable effects on interoception, attention and autonomic regulation; it could be used as a monotherapy or to address trauma treatment barriers.

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.

Multimodal structural neuroimaging markers of risk and recovery from posttrauma anhedonia: A prospective investigation.

BACKGROUND: Anhedonic symptoms of posttraumatic stress disorder (PTSD) reflect deficits in reward processing that have significant functional consequences. Although recent evidence suggests that disrupted integrity of fronto-limbic circuitry is related to PTSD development, including anhedonic PTSD symptoms (posttrauma anhedonia [PTA]), little is known about potential structural biomarkers of long-term PTA as well as structural changes in fronto-limbic pathways associated with recovery from PTA over time. METHODS: We investigated associations between white matter microstructure, gray matter volume, and PTA in 75 recently traumatized individuals, with a subset of participants (n = 35) completing follow-up assessment 12 months after trauma exposure. Deterministic tractography and voxel-based morphometry were used to assess changes in white and gray matter structure associated with changes in PTA. RESULTS: Reduced fractional anisotropy (FA) of the uncinate fasciculus at around the time of trauma predicted greater PTA at 12-months posttrauma. Further, increased FA of the fornix over time was associated with lower PTA between 1 and 12-months posttrauma. Increased gray matter volume of the ventromedial prefrontal cortex and precuneus over time was also associated with reduced PTA. CONCLUSIONS: The microstructure of the uncinate fasciculus, an amygdala-prefrontal white matter connection, may represent a biomarker of vulnerability for later PTA. Conversely, development and recovery from PTA appear to be facilitated by white and gray matter structural changes in a major hippocampal pathway, the fornix. The present findings shed new light on neuroanatomical substrates of recovery from PTA and characterize white matter biomarkers of risk for posttraumatic dysfunction.

Increased activation of the fear neurocircuitry in children exposed to violence.

Most studies investigating the effect of childhood trauma on the brain are retrospective and mainly focus on maltreatment, whereas different types of trauma exposure such as growing up in a violent neighborhood, as well as developmental stage, could have differential effects on brain structure and function. The current magnetic resonance imaging study assessed the effect of trauma exposure broadly and violence exposure more specifically, as well as developmental stage on the fear neurocircuitry in 8- to 14-year-old children and adolescents (N = 69). We observed reduced hippocampal and increased amygdala volume with increasing levels of trauma exposure. Second, higher levels of violence exposure were associated with increased activation in the amygdala, hippocampus, and ventromedial prefrontal cortex during emotional response inhibition. This association was specifically observed in children younger than 10 years. Finally, increased functional connectivity between the amygdala and brainstem was associated with higher levels of violence exposure. Based on the current findings, it could be hypothesized that trauma exposure during childhood results in structural changes that are associated with later risk for psychiatric disorders. At the same time, it could be postulated that growing up in an unsafe environment leads the brain to functionally adapt to this situation in a way that promotes survival, where the long-term costs or consequences of these adaptations are largely unknown and an area for future investigations.

Association between posttraumatic stress disorder severity and amygdala habituation to fearful stimuli.

BACKGROUND: Amygdala hyperreactivity to threat has been proposed to be a causal contributor to posttraumatic stress disorder (PTSD). However, emerging literature in healthy samples shows higher test-retest reliability for amygdala habituation (the change over time in response to repeated stimuli) than for its reactivity to threat. Amygdala habituation has received relatively little attention in relationship to PTSD, despite the key role of this region in the etiology of the disorder. Thus, we investigated habituation to repeated fearful face stimuli and PTSD, in a large sample of trauma exposed African American women. METHODS: African American women (N = 100) were recruited from a nonprofit hospital serving a largely low-income population with a high risk of trauma exposure. Participants underwent functional magnetic resonance imaging, passively viewing fearful and neutral face stimuli, and reported their history of trauma exposure and current PTSD symptoms. We examined associations between PTSD symptom severity and amygdala reactivity (fearful > neutral) and habituation (early > late) to fearful faces. Secondary analyses tested whether amygdala habituation to fearful faces mediated the association between childhood trauma and PTSD. RESULTS: PTSD symptom severity and PTSD status (based on self-report measure) were both positively associated with amygdala habituation to repeated fearful face stimuli. Whole-brain analysis showed that this association extended to the bilateral hippocampus and left fusiform gyrus. The association held when controlling for trauma history and depressive symptoms. Amygdala habituation to fearful faces partially mediated the association between childhood trauma severity and PTSD symptom severity. CONCLUSION: Individuals with greater PTSD symptom severity showed greater amygdala habituation to social threat cues (fearful faces), and greater habituation may partly explain the association between childhood trauma exposure and current PTSD symptoms. Further examination of the dynamics of the amygdala response to threat cues may lead to new insights in the understanding and treatment of stress-related disorders.

PACAP receptor gene polymorphism impacts fear responses in the amygdala and hippocampus.

We have recently found higher circulating levels of pituitary adenylate cyclase-activating polypeptide (PACAP) associated with posttraumatic stress disorder (PTSD) symptoms in a highly traumatized cohort of women but not men. Furthermore, a single nucleotide polymorphism in the PACAP receptor gene ADCYAP1R1, adenylate cyclase activating polypeptide 1 receptor type 1, was associated with individual differences in PTSD symptoms and psychophysiological markers of fear and anxiety. The current study outlines an investigation of individual differences in brain function associated with ADCYAP1R1 genotype. Forty-nine women who had experienced moderate to high levels of lifetime trauma participated in a functional MRI task involving passive viewing of threatening and neutral face stimuli. Analyses focused on the amygdala and hippocampus, regions that play central roles in the pathophysiology of PTSD and are known to have high densities of PACAP receptors. The risk genotype was associated with increased reactivity of the amygdala and hippocampus to threat stimuli and decreased functional connectivity between the amygdala and hippocampus. The findings indicate that the PACAP system modulates medial temporal lobe function in humans. Individual differences in ADCYAP1R1 genotype may contribute to dysregulated fear circuitry known to play a central role in PTSD and other anxiety disorders.

CHILDHOOD MALTREATMENT PREDICTS REDUCED INHIBITION-RELATED ACTIVITY IN THE ROSTRAL ANTERIOR CINGULATE IN PTSD, BUT NOT TRAUMA-EXPOSED CONTROLS.

BACKGROUND: A deficit in the ability to inhibit fear has been proposed as a biomarker of posttraumatic stress disorder (PTSD). Previous research indicates that individuals with PTSD show reduced inhibition-related activation in rostral anterior cingulate cortex (rACC). The goal of the current study was to investigate differential influences of an early environmental risk factor for PTSD-childhood maltreatment-on inhibition-related brain function in individuals with PTSD versus trauma-exposed controls. METHODS: Individuals with PTSD (n = 37) and trauma-exposed controls (n = 53) were recruited from the primary care waiting rooms of an urban public hospital in Atlanta, GA. Participants completed an inhibition task during fMRI, and reported childhood and adult traumatic experiences. The groups were matched for adult and child trauma load. RESULTS: We observed an interaction between childhood maltreatment severity and PTSD status in the rACC (P < .05, corrected), such that maltreatment was negatively associated with inhibition-related rACC activation in the PTSD group, but did not influence rACC activation in the TC group. Rostral ACC activation was associated with inhibition-related task performance in the TC group but not the PTSD group, suggesting a possible contribution to stress resilience. CONCLUSIONS: Findings highlight individual differences in neural function following childhood trauma, and point to inhibition-related activation in rostral ACC as a risk factor for PTSD.

Smaller hippocampal volume is associated with anxiety symptoms in high-risk Black youth.

Although there is an established link between smaller hippocampal volume and anxiety, the longitudinal relations between hippocampus structure and anxiety in diverse youth are not well understood. The present longitudinal study investigated hippocampal volumes related to anxiety symptoms in a sample of Black 8-14-year-old youth (N = 64), a population historically underrepresented in neuroimaging research. Smaller hippocampal volumes were associated with greater anxiety symptoms independent of age, sex, intracranial volume and trauma exposure. Exploratory longitudinal analyses showed smaller hippocampal volume as a predictor for anxiety symptoms (n = 37) and not a consequence of anxiety symptoms (n = 32), however results were inconclusive as this finding was no longer significant after correcting for baseline anxiety symptoms. Overall, this data increases our understanding of potential neurobiological mechanisms for anxiety in a high-risk sample of Black youth and suggests future directions into studying trajectories of developmental risk.

Civilian Moral Injury and Amygdala Functional Connectivity During Attention to Threat.

BACKGROUND: Moral injury references emotional and spiritual/existential suffering that may emerge following psychological trauma. Despite being linked to adverse mental health outcomes, little is known about the neurophysiological mechanisms of this phenomenon. In this study, we examined neural correlates of moral injury exposure and distress using the Moral Injury Exposure and Symptom Scale for Civilians. We also examined potential moderation of these effects by race (Black vs. White individuals) given the likely intersection of race-related stress with moral injury. METHODS: Forty-eight adults ages 18 to 65 years (mean age = 30.56, SD = 11.93) completed the Moral Injury Exposure and Symptom Scale for Civilians and an affective attentional control measure, the affective Stroop task (AS), during functional magnetic resonance imaging; the AS includes presentation of threat-relevant and neutral distractor stimuli. Voxelwise functional connectivity of the bilateral amygdala was examined in response to threat-relevant versus neutral AS distractor trials. RESULTS: Functional connectivity between the right amygdala and left postcentral gyrus/primary somatosensory cortex was positively correlated with the Moral Injury Exposure and Symptom Scale for Civilians exposure score (voxelwise p < .001, cluster false discovery rate-corrected p < .05) in response to threat versus neutral AS distractor trials. Follow-up analyses revealed significant effects of race; Black but not White participants demonstrated this significant pattern of amygdala-left somatosensory cortex connectivity. CONCLUSIONS: Increased exposure to potentially morally injurious events may lead to emotion-somatosensory pathway disruptions during attention to threat-relevant stimuli. These effects may be most potent for individuals who have experienced multilayered exposure to morally injurious events, including racial trauma. Moral injury appears to have a distinct neurobiological signature that involves abnormalities in connectivity of emotion-somatosensory paths, which may be amplified by race-related stress.

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.

Cortical similarities in psychiatric and mood disorders identified in federated VBM analysis via COINSTAC.

Structural neuroimaging studies have identified a combination of shared and disorder-specific patterns of gray matter (GM) deficits across psychiatric disorders. Pooling large data allows for examination of a possible common neuroanatomical basis that may identify a certain vulnerability for mental illness. Large-scale collaborative research is already facilitated by data repositories, institutionally supported databases, and data archives. However, these data-sharing methodologies can suffer from significant barriers. Federated approaches augment these approaches by enabling access or more sophisticated, shareable and scaled-up analyses of large-scale data. We examined GM alterations using Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation, an open-source, decentralized analysis application. Through federated analysis of eight sites, we identified significant overlap in the GM patterns (n = 4,102) of individuals with schizophrenia, major depressive disorder, and autism spectrum disorder. These results show cortical and subcortical regions that may indicate a shared vulnerability to psychiatric disorders.

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.

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.

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.

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.

Association between dimensions of trauma-related psychopathology and asthma in trauma-exposed women.

Introduction: Exposure to traumatic events and stressful life experiences are associated with a wide range of adverse mental and physical health outcomes. Studies have found post-traumatic stress disorder (PTSD), depression, and anxiety sensitivity occurrence to be common in addition to inflammatory diseases like asthma, especially in women. Moreover, overlapping neurobiological mechanisms have been linked to both PTSD and asthma. Methods: In the current study, n = 508 women reported on presence of lifetime asthma diagnosis and symptoms of trauma-related psychopathology including PTSD and depression. A separate group of female participants (n = 64) reported on asthma, PTSD, depression and anxiety sensitivity, and underwent functional MRI scans during a fearful faces task, and their anterior insula responses were analyzed. Results: Overall, PTSD and depression severity were significantly higher in those with asthma versus those without asthma. There was a positive association between anterior insula response to social threat cues and depression symptoms only among individuals without a lifetime presence of asthma. Discussion: These findings provide continued evidence on the interactions between stress, neural mechanisms involved in interoception and salience detection, and trauma-related psychopathology.