Experiences of racial discrimination and adverse gene expression among black individuals in a level 1 trauma center sample.

Up to 40 % of individuals who sustain traumatic injuries are at risk for posttraumatic stress disorder (PTSD) and the conditional risk for developing PTSD is even higher for Black individuals. Exposure to racial discrimination, including at both interpersonal and structural levels, helps explain this health inequity. Yet, the relationship between racial discrimination and biological processes in the context of traumatic injury has yet to be fully explored. The current study examined whether racial discrimination is associated with a cumulative measure of biological stress, the gene expression profile conserved transcriptional response to adversity (CTRA), in Black trauma survivors. Two-weeks (T1) and six-months (T2) post-injury, Black participants (N = 94) provided a blood specimen and completed assessments of lifetime racial discrimination and PTSD symptoms. Mixed effect linear models evaluated the relationship between change in CTRA gene expression and racial discrimination while adjusting for age, gender, body mass index (BMI), smoking history, heavy alcohol use history, and trauma-related variables (mechanism of injury, lifetime trauma). Results revealed that for individuals exposed to higher levels of lifetime racial discrimination, CTRA significantly increased between T1 and T2. Conversely, CTRA did not increase significantly over time in individuals exposed to lower levels of lifetime racial discrimination. Thus, racial discrimination appeared to lead to a more sensitized biological profile which was further amplified by the effects of a recent traumatic injury. These findings replicate and extend previous research elucidating the processes by which racial discrimination targets biological systems.

Racial discrimination increases the risk for nonremitting posttraumatic stress disorder symptoms in traumatically injured Black individuals living in the United States.

Traumatic, life-threatening events are experienced commonly among the general U.S. population, yet Black individuals in the United States (i.e., Black Americans) exhibit higher prevalence rates of posttraumatic stress disorder (PTSD) and more severe symptoms than other populations. Although empirical research has noted a range of symptom patterns that follow traumatic injury, minimal work has examined the role of racial discrimination in relation to PTSD symptom trajectories. The current study assessed racial discrimination and PTSD symptom trajectories at 6 months postinjury across two separate samples of traumatically injured Black Americans (i.e. emergency department (ED)-discharged and hospitalized). Identified PTSD symptom trajectories largely reflect those previously reported (i.e., ED: nonremitting, moderate, remitting, and resilient; hospitalized: nonremitting, delayed, and resilient), although the resilient trajectory was less represented than expected given past research (ED: 55.8%, n = 62; hospitalized: 46.9%, n = 38). Finally, higher racial discrimination was associated with nonremitting, ED: relative risk ratio (RR) = 1.32, hospitalized: RR = 1.23; moderate, ED: RR = 1.18; and delayed, hospitalized: RR = 1.26, PTSD symptom trajectories. Overall, the current findings not only emphasize the inimical effects of racial discrimination but also demonstrate the unique ways in which race-related negative events can impact PTSD symptom levels and recovery across time.

Attributional negativity bias and acute stress disorder symptoms mediate the association between trauma history and future posttraumatic stress disorder.

Individuals who have experienced more trauma throughout their life have a heightened risk of developing posttraumatic stress disorder (PTSD) following injury. Although trauma history cannot be retroactively modified, identifying the mechanism(s) by which preinjury life events influence future PTSD symptoms may help clinicians mitigate the detrimental effects of past adversity. The current study proposed attributional negativity bias, the tendency to perceive stimuli/events as negative, as a potential intermediary in PTSD development. We hypothesized an association between trauma history and PTSD symptom severity following a new index trauma via heightened negativity bias and acute stress disorder (ASD) symptoms. Recent trauma survivors (N =189, 55.5% women, 58.7% African American/Black) completed assessments of ASD, negativity bias, and lifetime trauma 2-weeks postinjury; PTSD symptoms were assessed 6 months later. A parallel mediation model was tested with bootstrapping (10,000 resamples). Both negativity bias, Path b1 : ß = -.24, t(187) = -2.88, p = .004, and ASD symptoms, Path b2 : ß = .30, t(187) = 3.71, p < .001, fully mediated the association between trauma history and 6-month PTSD symptoms, full model: F(6, 182) = 10.95, p < .001, R 2 = .27; Path c': ß = .04, t(187) = 0.54, p = .587. These results suggest that negativity bias may reflect an individual cognitive difference that can be further activated by acute trauma. Moreover, negativity bias may be an important, modifiable treatment target, and interventions addressing both acute symptoms and negativity bias in the early posttrauma period may weaken the link between trauma history and new-onset PTSD.

Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

Event centrality and posttraumatic stress symptoms after traumatic injury: A longitudinal investigation.

The development of posttraumatic stress symptoms (PTSS) can occur following a traumatic injury, which may include an increase in negative cognitions. One cognitive construct shown to be associated with the development of PTSS is event centrality, or the degree to which an individual views a traumatic experience as central to their life story. Although cross-sectional work has demonstrated a robust connection between event centrality and PTSS, the directionality of this association remains unclear. Most previous work has investigated centrality as a predictor of PTSS, although one recent study suggests that PTSS may, in fact, predict event centrality. The current longitudinal study enrolled adult civilian participants (N = 191) from a Level 1 trauma center following a traumatic injury and assessed both event centrality and PTSS at three points posttrauma (3, 12, and 18 months). A time-constrained random intercept cross-lagged panel analysis showed that PTSS predicted event centrality over the 18-month follow-up period, B = 0.16, p = .021, but event centrality did not predict PTSS, B = -0.27, p = .340. These findings suggest that the development of PTSS following trauma exposure may lead to the perception of the traumatic event as central to an individual's story over time. Further longitudinal research is necessary to determine what variables may influence the connection between PTSS and event centrality.

Machine learning prediction of posttraumatic stress disorder trajectories following traumatic injury: Identification and validation in two independent samples.

Due to its heterogeneity, the prediction of posttraumatic stress disorder (PTSD) development after traumtic injury is difficult. Recent machine learning approaches have yielded insight into predicting PTSD symptom trajectories. Using data collected within 1 month of traumatic injury, we applied eXtreme Gradient Boosting (XGB) to classify admitted and discharged patients (hospitalized, n = 192; nonhospitalized, n = 214), recruited from a Level 1 trauma center, according to PTSD symptom trajectories. Trajectories were identified using latent class mixed models on PCL-5 scores collected at baseline, 1-3 months posttrauma, and 6 months posttrauma. In both samples, nonremitting, remitting, and resilient PTSD symptom trajectories were identified. In the admitted patient sample, a unique delayed trajectory emerged. Machine learning classifiers (i.e., XGB) were developed and tested on the admitted patient sample and externally validated on the discharged sample with biological and clinical self-report baseline variables as predictors. For external validation sets, prediction was fair for nonremitting versus other trajectories, areas under the curve (AUC = .70); good for nonremitting versus resilient trajectories, AUCs = .73-.76; and prediction failed for nonremitting versus remitting trajectories, AUCs = .46-.48. However, poor precision (< .57) across all models suggests limited generalizability of nonremitting symptom trajectory prediction from admitted to discharged patient samples. Consistency in symptom trajectory identification across samples supports prior studies on the stability of PTSD symptom trajectories following trauma exposure; however, continued work and replication with larger samples are warranted to understand overlapping and unique predictive features of PTSD in different traumatic injury populations.

The role of pain and socioenvironmental factors on posttraumatic stress disorder symptoms in traumatically injured adults: A 1-year prospective study.

Approximately 20% of individuals who experience a traumatic injury will subsequently develop posttraumatic stress disorder (PTSD). Physical pain following traumatic injury has received increasing attention as both a distinct, functionally debilitating disorder and a comorbid symptom related to PTSD. Studies have demonstrated that both clinician-assessed injury severity and patient pain ratings can be important predictors of nonremitting PTSD; however, few have examined pain and PTSD alongside socioenvironmental factors. We postulated that both area- and individual-level socioeconomic circumstances and lifetime trauma history would be uniquely associated with PTSD symptoms and interact with the pain-PTSD association. To test these effects, pain and PTSD symptoms were assessed at four visits across a 1-year period in a sample of 219 traumatically injured participants recruited from a Level 1 trauma center. We used a hierarchal linear modeling approach to evaluate whether (a) patient-reported pain ratings were a better predictor of PTSD than clinician-assessed injury severity scores and (b) socioenvironmental factors, specifically neighborhood socioeconomic disadvantage, individual income, and lifetime trauma history, influenced the pain-PTSD association. Results demonstrated associations between patient-reported pain ratings, but not clinician-assessed injury severity scores, and PTSD symptoms, R2( fvm ) = .65. There was a significant interaction between neighborhood socioeconomic disadvantage and pain such that higher disadvantage decreased the strength of the pain-PTSD association but only among White participants, R2( fvm ) = .69. Future directions include testing this question in a larger, more diverse sample of trauma survivors (e.g., geographically diverse) and examining factors that may alleviate both pain and PTSD symptoms.

Neural substrates of human fear generalization: A 7T-fMRI investigation.

Fear generalization - the tendency to interpret ambiguous stimuli as threatening due to perceptual similarity to a learned threat - is an adaptive process. Overgeneralization, however, is maladaptive and has been implicated in a number of anxiety disorders. Neuroimaging research has indicated several regions sensitive to effects of generalization, including regions involved in fear excitation (e.g., amygdala, insula) and inhibition (e.g., ventromedial prefrontal cortex). Research has suggested several other small brain regions may play an important role in this process (e.g., hippocampal subfields, bed nucleus of the stria terminalis [BNST], habenula), but, to date, these regions have not been examined during fear generalization due to limited spatial resolution of standard human neuroimaging. To this end, we utilized the high spatial resolution of 7T fMRI to characterize the neural circuits involved in threat discrimination and generalization. Additionally, we examined potential modulating effects of trait anxiety and intolerance of uncertainty on neural activation during threat generalization. In a sample of 31 healthy undergraduate students, significant positive generalization effects (i.e., greater activation for stimuli with increasing perceptual similarity to a learned threat cue) were observed in the visual cortex, thalamus, habenula and BNST, while negative generalization effects were observed in the dentate gyrus, CA1, and CA3. Associations with individual differences were underpowered, though preliminary findings suggested greater generalization in the insula and primary somatosensory cortex may be correlated with self-reported anxiety. Overall, findings largely support previous neuroimaging work on fear generalization and provide additional insight into the contributions of several previously unexplored brain regions.

Racial Discrimination is Associated with Acute Posttraumatic Stress Symptoms and Predicts Future Posttraumatic Stress Disorder Symptom Severity in Trauma-Exposed Black Adults in the United States.

In the United States, Black residents exposed to a traumatic event are at an increased risk of developing posttraumatic stress disorder (PTSD) and experiencing more severe symptoms compared to their non-Hispanic White counterparts. Although previous work has suggested a link between racial discrimination and PTSD symptoms, no studies have assessed this association in a sample of traumatic injury survivors. The current study investigated whether (a) past racial discrimination was associated with acute posttraumatic stress symptoms (PTSS) and (b) discrimination prospectively contributed to the prediction of future PTSD symptoms. African American and/or Black patients (N = 113) were recruited from an emergency department in southeastern Wisconsin. Patients in the acute postinjury phase (i.e., 2 weeks posttrauma) completed self-report measures, with PTSD symptoms assessed using the Clinician-Administered PTSD Scale at 6-month follow-up. Bivariate associations indicated past racial discrimination was significantly related to acute PTSS. A multiple regression analysis revealed that pretrauma exposure to racial discrimination significantly predicted PTSD symptoms at follow-up, even after controlling for age, gender, previous psychiatric diagnosis, social support, and lifetime trauma history. Our results suggest that experiences of racial discrimination add significant additional risk for PTSD symptom development following traumatic injury, R2 = .16, F(6, 106) = 3.25, p = .006. Broadly, these findings add to the body of empirical evidence and personal testimonies of Black individuals in White-centric societies asserting that racial discrimination affects mental health and overall well-being and further highlight the recent call for racism to be classified as a public health crisis.

A Randomized Trial of Modified Prolonged Exposure to Prevent the Development of Posttraumatic Stress Disorder in Patients Hospitalized With Traumatic Injuries.

Individuals who require hospitalization after traumatic injuries are at increased risk for developing posttraumatic stress disorder (PTSD); however, few early behavioral interventions have been effective at preventing PTSD within this population. The aim of this pilot study was to assess the feasibility and effectiveness of modified prolonged exposure therapy (mPE) to prevent PTSD and depression symptoms among patients hospitalized after a DSM-5 single-incident trauma. Hospitalized patients were eligible if they screened positive for PTSD risk. Participants (N = 74) were randomly assigned in a parallel-groups design to receive mPE (n = 38) or standard of care treatment (SoC; n = 36) while admitted to the hospital after a traumatic injury. Individuals randomized to the intervention condition received one (42.1%), two (36.8%), or three sessions (15.8%) of mPE, mainly depending on length of stay. There were no significant differences between groups regarding PTSD or depression severity at 1- or 3-months posttrauma, except for more PTSD diagnoses in the intervention group after 1 month, ϕ = -.326. Intervention differences were nonsignificant when we took baseline PTSD symptoms and the nonindependence of the repeated measurements within the data into account. No adverse events were reported. Overall, mPE was no more effective than SoC for hospitalized, traumatic injury survivors with a high PTSD risk. The results may point to a need for a stepped-care approach, where intervention protocols focus on first briefly treating individuals who are actively exhibiting acute stress reactions, then extensively treating those whose symptoms do not decrease over time.

Disentangling the effects of novelty, valence and trait anxiety in the bed nucleus of the stria terminalis, amygdala and hippocampus with high resolution 7T fMRI.

The hippocampus and amygdala exhibit sensitivity to stimulus novelty that is reduced in participants with inhibited temperament, which is related to trait anxiety. Although the bed nucleus of the stria terminalis (BNST) is highly connected to the amygdala and is implicated in anxiety, whether the BNST responds to novelty remains unstudied, as well as how trait anxiety may modulate this response. Additionally how novelty, stimulus negativity and trait anxiety interact to affect activity in these areas is also unclear. To address these questions, we presented participants with novel and repeated, fearful and neutral faces, while measuring brain activity via fMRI, and also assessed participants' self-reported trait anxiety. As the small size of the BNST makes assessing its activity at typical fMRI resolution difficult, we employed high resolution 7 Tesla scanning. Our results replicate findings of novelty sensitivity that is independent of valence in the hippocampus. Our results also provide novel evidence for a BNST novelty response toward neutral, but not fearful faces. We also found that the novelty response in the hippocampus and BNST was blunted in participants with high trait anxiety. Additionally, we found left amygdala sensitivity to stimulus negativity that was blunted for high trait anxiety participants. These findings extend past research on the response to novel stimuli in the hippocampus and amygdala at high resolution, and are the first to demonstrate trait anxiety modulated novelty sensitivity in the BNST that is dependent on stimulus valence.

BAS Reward Responsiveness: A unique predictor of positive psychological functioning.

Previous research on Reinforcement Sensitivity Theory has well-characterized the Behavioral Inhibition System in terms of its behavioral and emotional manifestations, but the Behavioral Approach System (BAS) is less well-defined, particularly regarding the prominence of reward sensitivity versus impulsivity. Furthermore, few researchers evaluate both systems in one model. We evaluated the relationship between Carver and White's (1994) BIS/BAS Scales and areas of psychological functioning including internalizing, externalizing, affect regulation, and well-being. 497 undergraduates completed a battery of self-report measures. Two structural equation models indicate that the Reward Responsiveness subscale uniquely predicts adaptive functioning across all domains. Reward Responsiveness may be a more pure measure of BAS than other BAS traits and may be important for resilience from maladaptive psychological functioning.

Subtypes of childhood maltreatment and posttraumatic stress disorder symptoms in an adult trauma sample: The mechanistic role of sleep.

OBJECTIVE: Childhood maltreatment is indisputably linked to adverse mental health outcomes, including an increased risk to develop posttraumatic stress disorder (PTSD) in adulthood. The role of childhood maltreatment in the context of recovery from a trauma later in adulthood is not well understood. A variable related to both childhood maltreatment and PTSD symptoms, and a potential link between the two, is sleep. The current study aimed to understand how sleep disturbances may play a mechanistic role in the effect of subtypes of childhood maltreatment on PTSD symptom severity in an adult trauma sample. METHOD: 160 adults (90 women; Mage = 33.73, SD = 10.86) were recruited from the emergency department at a Level-1 trauma center in southeastern Wisconsin after experiencing a traumatic injury. Experiences of childhood maltreatment and sleep were self-reported at 2-week and 3-month posttrauma, respectively. PTSD symptoms were clinically assessed 6 months later. RESULTS: Sleep disturbances 3-month posttrauma mediated the effect of emotional abuse, physical neglect, and emotional neglect on PTSD symptom 6 months after the traumatic injury. The effect of sexual and physical abuse on PTSD symptoms was not significantly mediated by sleep disturbances. CONCLUSIONS: These findings highlight the differential impact of subtypes of childhood maltreatment on PTSD symptoms, the mechanistic role of sleep, and the need to consider early life adversity when assessing adult posttrauma experiences. These results also suggest that interventions aimed at improving sleep quality might improve PTSD symptoms in those who have experienced childhood maltreatment and a subsequent traumatic injury in adulthood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Trajectories of Anhedonia Symptoms after Traumatic Injury.

Anhedonia describes the inability or difficulty of experiencing or seeking pleasure. Previous research has demonstrated a relationship between posttraumatic stress disorder (PTSD) or experiencing trauma and anhedonia symptoms; however, little to no work has been done to understand the evolution of anhedonia symptoms after trauma. We aimed to identify anhedonia trajectories following traumatic injury. One hundred ninety-five participants were recruited from the emergency department of a Level-1 Trauma Center after experiencing a traumatic injury. To measure anhedonia symptoms, participants completed the Snaith-Hamilton Pleasure Scale (SHAPS) at 2-weeks, 3-months, and 6-months post-injury. Using latent class mixture modeling, we ran a trajectory analysis with three timepoints of SHAPS scores and compared mental and physical health outcomes across trajectories. Most of the sample fell in the resilient trajectory (85%), while the remainder were in a remitting trajectory (7%) where symptoms decreased over time, and a delayed (6%) trajectory where symptoms did not emerge until 3-months after injury. In the resilient trajectory, there was consistently low levels of PTSD, pain, depression, and anxiety relative to the other trajectories. In the delayed trajectory, depression and PTSD were chronically elevated and pain levels were consistent but mild. In the remitting trajectory, PTSD and depression symptoms decreased over time. Identified anhedonia trajectories mirrored trajectories commonly reported for PTSD symptoms after injury. Evaluating anhedonia trajectories and how they relate to mental health outcomes may inform targeted interventions for traumatic injury patients.

Childhood Maltreatment and Amygdala-Mediated Anxiety and Posttraumatic Stress Following Adult Trauma.

Background: Childhood abuse (physical, emotional, and sexual) is associated with aberrant connectivity of the amygdala, a key threat-processing region. Heightened amygdala activity also predicts adult anxiety and posttraumatic stress disorder (PTSD) symptoms, as do experiences of childhood abuse. The current study explored whether amygdala resting-state functional connectivity may explain the relationship between childhood abuse and anxiety and PTSD symptoms following trauma exposure in adults. Methods: Two weeks posttrauma, adult trauma survivors (n = 152, mean age [SD] = 32.61 [10.35] years; women = 57.2%) completed the Childhood Trauma Questionnaire and underwent resting-state functional magnetic resonance imaging. PTSD and anxiety symptoms were assessed 6 months posttrauma. Seed-to-voxel analyses evaluated the association between childhood abuse and amygdala resting-state functional connectivity. A mediation model evaluated the potential mediating role of amygdala connectivity in the relationship between childhood abuse and posttrauma anxiety and PTSD. Results: Childhood abuse was associated with increased amygdala connectivity with the precuneus while covarying for age, gender, childhood neglect, and baseline PTSD symptoms. Amygdala-precuneus resting-state functional connectivity was a significant mediator of the effect of childhood abuse on anxiety symptoms 6 months posttrauma (B = 0.065; 95% CI, 0.013-0.130; SE = 0.030), but not PTSD. A secondary mediation analysis investigating depression as an outcome was not significant. Conclusions: Amygdala-precuneus connectivity may be an underlying neural mechanism by which childhood abuse increases risk for anxiety following adult trauma. Specifically, this heightened connectivity may reflect attentional vigilance for threat or a tendency toward negative self-referential thoughts. Findings suggest that childhood abuse may contribute to longstanding upregulation of attentional vigilance circuits, which makes one vulnerable to anxiety-related symptoms in adulthood.

Experiences of childhood abuse are related to long-term mental health outcomes, but the mechanisms of this relationship have been unclear. In this study of adult trauma survivors, Harb et al. found that experiences of childhood abuse are related to abnormal connectivity patterns of the amygdala, a key region for fear and threat processing, and precuneus. These connectivity patterns were identified as a mechanism through which experiences of child abuse are related to adult anxiety symptoms posttrauma. These findings advance our understanding of the specific downstream impacts of experiencing childhood abuse and can inform targeted assessment and intervention methods, especially in an adult trauma sample.

Childhood adversity is associated with reduced BOLD response in inhibitory control regions amongst preadolescents from the ABCD study.

Adolescence is characterized by dynamic neurodevelopment, which poses opportunities for risk and resilience. Adverse childhood experiences (ACEs) confer additional risk to the developing brain, where ACEs have been associated with alterations in functional magnetic resonance imaging (fMRI) BOLD signaling in brain regions underlying inhibitory control. Socioenvironmental factors like the family environment may amplify or buffer against the neurodevelopmental risks associated with ACEs. Using baseline to Year 2 follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study, the current study examined how ACEs relate to fMRI BOLD signaling during successful inhibition on the Stop Signal Task in regions associated with inhibitory control and examined whether family conflict levels moderated that relationship. Results showed that greater ACEs were associated with reduced BOLD response in the right opercular region of the inferior frontal gyrus and bilaterally in the pre-supplementary motor area, which are key regions underlying inhibitory control. Further, greater BOLD response was correlated with less impulsivity behaviorally, suggesting reduced activation may not be behaviorally adaptive at this age. No significant two or three-way interactions with family conflict levels or time were found. Findings highlight the continued utility of examining the relationship between ACEs and neurodevelopmental outcomes and the importance of intervention/prevention of ACES.

The Dichotomy of Threat and Deprivation as Subtypes of Childhood Maltreatment: Differential Functional Connectivity Patterns of Threat and Reward Circuits in an Adult Trauma Sample.

BACKGROUND: Childhood maltreatment is associated with reduced activation of the nucleus accumbens, a central region in the reward network, and overactivity in the amygdala, a key region in threat processing. However, the long-lasting impact of these associations in the context of later-life stress is not well understood. The current study explored the association between childhood threat and deprivation and functional connectivity of threat and reward regions in an adult trauma sample. METHODS: Trauma survivors (N = 169; mean age [SD] = 32.2 [10.3] years; female = 55.6%) were recruited from a level I trauma center. Two weeks after injury, participants completed the Childhood Trauma Questionnaire (measuring experiences of threat and deprivation) and underwent resting-state functional magnetic resonance imaging. Seed-to-voxel analyses evaluated the effect of childhood threat and deprivation on amygdala and nucleus accumbens resting-state connectivity. RESULTS: Higher levels of threat were associated with increased connectivity between the right nucleus accumbens with temporal fusiform gyrus/parahippocampal gyrus and the left amygdala and the precuneus (false discovery rate-corrected p < .05). After controlling for posttraumatic symptoms 2 weeks posttrauma and lifetime trauma exposure, only the nucleus accumbens findings survived. There were no significant relationships between experiences of childhood deprivation and amygdala or nucleus accumbens connectivity. CONCLUSIONS: Experiences of threat are associated with increased nucleus accumbens and amygdala connectivity, which may reflect a preparedness to detect salient and visual stimuli. This may also reflect a propensity toward dysregulated reward processing. Overall, these results suggest that childhood threat may be contributing to aberrant neural baseline reward and threat sensitivity later in life in an adult trauma sample.

Intrusive Traumatic Re-Experiencing Domain: Functional Connectivity Feature Classification by the ENIGMA PTSD Consortium.

Background: Intrusive traumatic re-experiencing domain (ITRED) was recently introduced as a novel perspective on posttraumatic psychopathology, proposing to focus research of posttraumatic stress disorder (PTSD) on the unique symptoms of intrusive and involuntary re-experiencing of the trauma, namely, intrusive memories, nightmares, and flashbacks. The aim of the present study was to explore ITRED from a neural network connectivity perspective. Methods: Data were collected from 9 sites taking part in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) PTSD Consortium (n= 584) and included itemized PTSD symptom scores and resting-state functional connectivity (rsFC) data. We assessed the utility of rsFC in classifying PTSD, ITRED-only (no PTSD diagnosis), and trauma-exposed (TE)-only (no PTSD or ITRED) groups using a machine learning approach, examining well-known networks implicated in PTSD. A random forest classification model was built on a training set using cross-validation, and the averaged cross-validation model performance for classification was evaluated using the area under the curve. The model was tested using a fully independent portion of the data (test dataset), and the test area under the curve was evaluated. Results: rsFC signatures differentiated TE-only participants from PTSD and ITRED-only participants at about 60% accuracy. Conversely, rsFC signatures did not differentiate PTSD from ITRED-only individuals (45% accuracy). Common features differentiating TE-only participants from PTSD and ITRED-only participants mainly involved default mode network-related pathways. Some unique features, such as connectivity within the frontoparietal network, differentiated TE-only participants from one group (PTSD or ITRED-only) but to a lesser extent from the other group. Conclusions: Neural network connectivity supports ITRED as a novel neurobiologically based approach to classifying posttrauma psychopathology.

The interplay of attention and emotion: top-down attention modulates amygdala activation in psychopathy.

Psychopathic behavior has long been attributed to a fundamental deficit in fear that arises from impaired amygdala function. Growing evidence has demonstrated that fear-potentiated startle (FPS) and other psychopathy-related deficits are moderated by focus of attention, but to date, no work on adult psychopathy has examined attentional modulation of the amygdala or concomitant recruitment of relevant attention-related circuitry. Consistent with previous FPS findings, here we report that psychopathy-related differences in amygdala activation appear and disappear as a function of goal-directed attention. Specifically, decreased amygdala activity was observed in psychopathic offenders only when attention was engaged in an alternative goal-relevant task prior to presenting threat-relevant information. Under this condition, psychopaths also exhibited greater activation in selective-attention regions of the lateral prefrontal cortex (LPFC) than did nonpsychopaths, and this increased LPFC activation mediated psychopathy's association with decreased amygdala activation. In contrast, when explicitly attending to threat, amygdala activation did not differ in psychopaths and nonpsychopaths. This pattern of amygdala activation highlights the potential role of LPFC in mediating the failure of psychopathic individuals to process fear and other important information when it is peripheral to the primary focus of goal-directed attention.