Evaluating the impact of a street outreach intervention on participant involvement in gun violence.

The past several years have witnessed increased calls for community violence interventions (CVIs) that address firearm violence while centering local expertise and avoiding the criminal legal system. Currently, little evidence exists on CVI effectiveness at the individual level. This study presents an evaluation of the impact of a street outreach-based CVI [Chicago CRED (Create Real Economic Destiny)] on participant involvement in violence. We used a quasiexperimental design with a treatment sample of 324 men recruited by outreach staff from 2016 to 2021 and a balanced comparison sample of 2,500 men from a network of individuals arrested in CRED's service areas. We conducted a Bayesian survival analysis to evaluate CRED's effect on individual violence-related outcomes on three levels of treatment: All enrolled participants, a subsample that made it through the initial phase, and those who completed programming. The intervention had a strong favorable effect on the probability of arrest for a violent crime for those completing the program: After 24 mo, CRED alumni experienced an 11.3 percentage point increase in survival rates of arrest for a violent crime relative to their comparisons (or, stated differently, a 73.4% reduction in violent crime arrests). The other two treatment levels experienced nontrivial declines in arrests but did not reach statistical significance. No statistically significant reduction in victimization risk was detected for any of the treatment levels. Results demonstrate that completion of violence intervention programming reduces the likelihood of criminal legal involvement for participants, despite the numerous systemic and environmental factors that impede personal success.

The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD.

BACKGROUND: Posttraumatic Stress Disorder (PTSD) is commonly treated with exposure-based cognitive therapies that are based on the principles of fear acquisition and extinction learning. Elevations in one of the major endocannabinoids (anandamide) either via inhibition of the primary degrading enzyme (fatty acid amide hydrolase; FAAH) or via a genetic variation in the FAAH gene (C385A; rs324420) has resulted in accelerated extinction learning and enhanced extinction recall among healthy adults. These results suggest that targeting FAAH may be a promising therapeutic approach for PTSD. However, these effects have not yet been comprehensively examined in a PTSD population. METHODS: The current study examined whether genetic variation in the FAAH gene (CC [n = 49] vs AA/AC [n = 36] allele carriers) influences physiological (skin conductance), cognitive (threat expectancy), and neural (network and voxel-wise activation) indices of fear acquisition and extinction learning among a sample of adult women with PTSD (N = 85). RESULTS: The physiological, cognitive, and neural signatures of fear acquisition and extinction learning varied as a function of whether or not individuals possess the FAAH C385A polymorphism. For instance, we report divergent responding between CC and AA/AC allele carriers to CS + vs CS- in limbic and striatum networks and overall greater activation throughout the task among AA/AC allele carriers in several regions [e.g., inferior frontal, middle frontal, parietal] that are highly consistent with a frontoparietal network involved in higher-order executive functions. CONCLUSIONS: These results suggest that genetic variation within the FAAH gene influences physiological, cognitive, and neural signatures of fear learning in women with PTSD. In order to advance our understanding of the efficacy of FAAH inhibition as a treatment for PTSD, future clinical trials in this area should assess genetic variation in the FAAH gene in order to fully depict and differentiate the acute effects of a drug manipulation (FAAH inhibition) from more chronic (genetic) influences on fear extinction processes.

Functional imaging correlates of childhood trauma: A qualitative review of past research and emerging trends.

Childhood trauma exposure is common and is associated with poor clinical outcomes in adolescence along with mental health and sociodemographic challenges in adulthood. While many strategies exist to investigate the biological imprint of childhood trauma exposure, functional neuroimaging is a robust and growing technology for non-invasive studies of brain activity following traumatic experience and the relationship of childhood trauma exposure with psychopathology, cognition, and behavior. In this review, we discuss three popular approaches for discerning functional neural correlates to early life trauma, including regional activation, bivariate functional connectivity, and network-based connectivity. The breadth of research in each method is discussed, followed by important limitations and considerations for future research. We close by considering emerging trends in functional neuroimaging research of childhood trauma, including the use of complex decision-making tasks to mimic clinically-relevant behaviors, data-driven techniques such as multivariate pattern analysis and whole-brain network topology, and the applications of real-time neurofeedback for treatment of trauma-related mental disorders. We aim for this review to provide a framework for understanding the relationship between atypical neural functioning and adverse outcomes following childhood trauma exposure, with a focus on improving consistency in research methods and translatability of research findings for clinical settings.

Unique neurocircuitry activation profiles during fear conditioning and extinction among women with posttraumatic stress disorder.

BACKGROUND: Neurocircuitry models of posttraumatic stress disorder (PTSD) suggest specific alterations in brain structures linked with fear conditioning and extinction. Most models assume a unitary pattern of neurocircuitry dysfunction in PTSD and little attention has focused on defining unique profiles of neurocircuitry engagement (i.e., biotypes), despite known clinical heterogeneity in PTSD. Here, we aim to address this gap using a data-driven approach to characterize unique neurocircuitry profiles among women with PTSD. METHODS: Seventy-six women with PTSD related to assaultive violence exposure competed a task during fMRI that alternated between fear conditioning, where a geometric shape predicted the occurrence of an electric shock, and fear extinction, where the geometric shape no longer predicted electric shock. A multivariate clustering analysis was applied to neurocircuitry patterns constrained within an a priori mask of structures linked with emotion processing. Resulting biotypes were compared on clinical measures of neurocognition, trauma exposure, general mental health symptoms, and PTSD symptoms and on psychophysiological responding during the task. RESULTS: The clustering analysis identified three biotypes (BT), differentiated by patterns of engagement within salience, default mode, and visual processing networks. BT1 was characterized by higher working memory, fewer general mental health symptoms, and low childhood sexual abuse, and lower PTSD symptom severity. BT2 was characterized by lower verbal IQ but better extinction learning as defined by psychophysiology and threat expectancy. BT3 was characterized by low childhood sexual abuse, anxious arousal, and re-experiencing symptoms. CONCLUSION: This data demonstrates unique profiles of neurocircuitry engagement in PTSD, each associated with different clinical characteristics, and suggests further research defining distinct biotypes of PTSD. Clinicaltrials.gov, https://clinicaltrials.gov/ct2/home, NCT02560389.

Gray matter volume correlates of adolescent posttraumatic stress disorder: A comparison of manual intervention and automated segmentation in FreeSurfer.

Exposure to early life trauma is common and confers risk for psychological disorders in adolescence, including posttraumatic stress disorder (PTSD). Trauma exposure and PTSD are also consistently linked to alterations in gray matter volume (GMV). Despite the quantity of structural neuroimaging research in trauma-exposed populations, little consensus exists amongst research groups on best practices for image processing method and manual editing procedures. The purpose of this report is to evaluate the utility of manual editing of magnetic resonance (MR) images for detecting PTSD-related group differences in GMV. Here, T1-weighted MR images from adolescent girls aged 11-17 were obtained and analyzed. Two datasets were created from the FreeSurfer reconall pipeline, one of which was manually edited by trained research assistants. Gray matter regions of interest were selected and total volume estimates were entered into linear mixed effects models with method (manual edits or automated) as a within-subjects factor and group dummy-coded with PTSD as the reference group. Consistent with prior literature, individuals with PTSD demonstrated reduced GMV of the amygdala compared to trauma-exposed and non-trauma exposed controls, independent of editing method. Our results demonstrate that amygdala GMV reductions in PTSD are robust to certain methodological choices and do not suggest a benefit to the time-intensive manual editing pipeline in FreeSurfer for quantifying PTSD-related GMV.

Differential relationships of PTSD symptom clusters with cortical thickness and grey matter volumes among women with PTSD.

Structural neuroimaging studies of posttraumatic stress disorder (PTSD) have typically reported reduced cortical thickness (CT) and gray matter volume (GMV) in subcortical structures and networks involved in memory retrieval, emotional processing and regulation, and fear acquisition and extinction. Although PTSD is more common in women, and interpersonal violence (IPV) exposure is a more potent risk factor for developing PTSD relative to other forms of trauma, most of the existing literature examined combat-exposed men with PTSD. Vertex-wise CT and subcortical GMV analyses were conducted to examine potential differences in a large, well-characterized sample of women with PTSD stemming from IPV-exposure (n = 99) compared to healthy trauma-free women without a diagnosis of PTSD (n = 22). Subgroup analyses were also conducted to determine whether symptom severity within specific PTSD symptom clusters (e.g., re-experiencing, active avoidance, hyperarousal) predict CT and GMV after controlling for comorbid depression and anxiety. Results indicated that a diagnosis of PTSD in women with IPV-exposure did not significantly predict differences in CT across the cortex or GMV in the amygdala or hippocampus compared to healthy controls. However, within the PTSD group, greater re-experiencing symptom severity was associated with decreased CT in the left inferior and middle temporal gyrus, and decreased CT in the right parahippocampal and medial temporal gyrus. In contrast, greater active avoidance symptom severity was associated with greater CT in the left lateral fissure, postcentral gyrus, and middle/lateral occipital cortex, and greater CT in the right paracentral, posterior cingulate, and superior occipital gyrus. In terms of GMV, greater hyperarousal symptom severity was associated with reduced left amygdala GMV, while greater active avoidance symptom severity was associated with greater right amygdala GMV. These findings suggest that structural brain alterations among women with IPV-related PTSD may be driven by symptom severity within specific symptom clusters and that PTSD symptom clusters may have a differential (increased or decreased) association with brain structures.

Distinct cortical thickness correlates of early life trauma exposure and posttraumatic stress disorder are shared among adolescent and adult females with interpersonal violence exposure.

Early life trauma (ELT) exposure and posttraumatic stress disorder (PTSD) both affect neural structure, which predicts a variety of mental health concerns throughout the lifespan and may present differently between adolescents and adults. However, few studies have identified the relationship between ELT, PTSD, development, and brain structure using cortical thickness (CT). CT may reveal previously obscured alterations that are potentially clinically relevant and, furthermore, could identify specific structural correlates distinct to ELT from PTSD. Two hundred and fifty-three female adolescent and adult survivors of interpersonal violence and non-trauma-exposed demographically matched controls underwent structural MRI at two different sites. Images were processed and CT was estimated using FreeSurfer. Vertex-wise linear model tests were conducted across the cortical surface to investigate whether PTSD and ELT exposure uniquely affect CT, controlling for scanner site. Planned follow-up tests included second-level analyses of clinical symptoms for CT clusters that were significantly related to PTSD or ELT. CT in the middle cingulate cortex was inversely related to ELT in both age groups, such that individuals with more ELT demonstrated less CT in this region. Additionally, CT was significantly greater in the bilateral intraparietal sulcus and left angular gyrus in both adolescents and adults with PTSD. Furthermore, CT in these clusters was also significantly related to clinical symptom severity in the adult PTSD group. This study provides evidence for distinct CT correlates of ELT and PTSD that are present across adolescents and adults, suggesting consistent markers related to ELT and PTSD on gray matter structure in trauma-exposed individuals.

Altered large-scale functional brain organization in posttraumatic stress disorder: A comprehensive review of univariate and network-level neurocircuitry models of PTSD.

Classical neural circuitry models of posttraumatic stress disorder (PTSD) are largely derived from univariate activation studies and implicate the fronto-limbic circuit as a main neural correlate of PTSD symptoms. Though well-supported by human neuroimaging literature, these models are limited in their ability to explain the widely distributed neural and behavioral deficits in PTSD. Emerging interest in the application of large-scale network methods to functional neuroimaging provides a new opportunity to overcome such limitations and conceptualize the neural circuitry of PTSD in the context of network patterns. This review aims to evaluate both the classical neural circuitry model and a new, network-based model of PTSD neural circuitry using a breadth of functional brain organization research in subjects with PTSD. Taken together, this literature suggests global patterns of reduced functional connectivity (FC) in PTSD groups as well as altered FC targets that reside disproportionately in canonical functional networks, especially the default mode network. This provides evidence for an integrative model that includes elements of both the classical models and network-based models to characterize the neural circuitry of PTSD.

Estradiol Modulates Neural and Behavioral Arousal in Women With Posttraumatic Stress Disorder During a Fear Learning and Extinction Task.

BACKGROUND: Fear responding in posttraumatic stress disorder (PTSD) is sexually heterogeneous and varies with hormonal fluctuations throughout the menstrual cycle. While research suggests that estrogen levels affect PTSD symptoms among women, there is a dearth of research on modulatory effects of estrogen on fear responding among women with PTSD, and neural outcome measures are lacking. METHODS: A sample of 42 women with PTSD underwent 2 consecutive alternating blocks of fear conditioning and extinction training, during which a CS+ conditioned stimulus, but not a CS-, predicted the occurrence of an electric shock in an acquisition context but not in an extinction context. Assayed saliva determined estradiol levels. Skin conductance response and whole-brain voxelwise activity during functional magnetic resonance imaging were outcome variables in linear mixed-effects models, with estradiol level, PTSD severity, and task contrasts as predictors. RESULTS: Skin conductance response exhibited a significant estradiol × PTSD severity × habituation interaction (t = 3.180, p = .002), such that PTSD severity was correlated with increased arousal responding between training blocks among women with lower estradiol (t = -3.985, p < .001) but not higher estradiol (t = 0.550, p = .583). Voxelwise activity also demonstrated an identical three-way interaction within dorsomedial prefrontal cortex and anterior insula clusters. The skin conductance response and imaging interactions between PTSD severity and estradiol were not specific to conditioned stimulus type or context. CONCLUSIONS: Estradiol moderated the relationship between PTSD severity and arousal response habituation between fear conditioning and extinction training sessions, such that high estradiol protected against the negative impact of severe PTSD symptoms on fear habituation. These findings suggest that estrogen enhances habituation among women with severe PTSD, potentially influencing the efficacy of extinction-based therapies.

Sacrificing reward to avoid threat: Characterizing PTSD in the context of a trauma-related approach-avoidance conflict task.

Posttraumatic stress disorder (PTSD) is characterized by heightened avoidance, cognitive inflexibility, and impaired reward processing. Maladaptive behavior in PTSD may reflect an imbalance between approach and avoidance, but no research has investigated approach-avoidance conflict (AAC) in PTSD. The current study investigated approach-avoidance behavior in PTSD using a trauma-related AAC (trAAC) task in two independent samples. In Study 1, 43 women with a current diagnosis of PTSD and 18 healthy comparison subjects were recruited from the community. In Study 2, 53 women with trauma exposure and a range of PTSD symptoms were recruited from a correctional institution. Trials were separated into two phases: conflict (the option most likely to win points was most likely to show a trauma-related image) and congruent (the option most likely to win points was least likely to show a trauma-related image). In Study 1, reward obtainment varied with the task manipulation (i.e., fewer points earned during conflict compared to congruent Phase) in PTSD but not healthy subjects. These results indicate that when avoidance is advantageous (congruent phase), individuals with PTSD show increased task performance, whereas when avoidance is maladaptive (conflict phase), individuals with PTSD show increased sacrifice of reward. In Study 2, higher PTSD symptoms predicted decreased reward earning during the conflict phase, again indicating a sacrifice of reward when avoidance is maladaptive. Across both studies, PTSD associated with increased AAC and sacrifice of reward in the presence of trauma-related stimuli. These studies shed light on AAC in PTSD and could inform more targeted therapy approaches. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Biotypes of functional brain engagement during emotion processing differentiate heterogeneity in internalizing symptoms and interpersonal violence histories among adolescent girls.

Youth exposed to early life interpersonal violence (IPV) demonstrate heterogeneous clinical symptoms. Studies based on univariate methods suggest that neurocircuitry related to emotion processing explains heterogeneity in internalizing symptoms. Here, we use a multivariate, data-driven method of identifying distinct functional brain activation profiles (i.e., "biotypes") and test whether these biotypes differentiate internalizing symptoms among IPV-exposed youth. 114 adolescent girls (n = 38 with no IPV exposure or psychopathology; n = 76 with IPV exposure and heterogeneous internalizing symptoms), aged 11-17, completed an emotion processing task during fMRI. To identify distinct biotypes of brain engagement profiles, data-driven clustering analysis was applied to patterns of voxel activation, constrained within a mask of distributed regions implicated in emotion processing. Resulting biotypes (BT1-3) were compared on measures of IPV exposure and internalizing symptoms, as well as symptom reduction during Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) among a subset of participants (n = 21). Cluster analyses identified three biotypes, differentiated by engagement of medial prefrontal, anterior insula, hippocampus, parietal, and ventral visual cortex during emotion processing. BT1 exhibited low levels of IPV exposure and internalizing symptoms. BT2 exhibited elevated levels of IPV, except sexual assault, and demonstrated moderate severity across internalizing symptom domains. BT3 exhibited elevated severity across all IPV and internalizing symptom domains. Greater symptom reduction during TF-CBT was associated with increased pre-to post-treatment changes in similarity with BT1. These results demonstrate distinct profiles of emotion processing neurocircuitry that differentiate heterogeneity in internalizing symptoms in IPV-exposed adolescent girls.

Abnormal Prefrontal Development in Pediatric Posttraumatic Stress Disorder: A Longitudinal Structural and Functional Magnetic Resonance Imaging Study.

BACKGROUND: Prior studies of pediatric posttraumatic stress disorder (PTSD) have reported cross-sectional and age-related structural and functional brain abnormalities in networks associated with cognitive, affective, and self-referential processing. However, no reported studies have comprehensively examined longitudinal gray matter development and its intrinsic functional correlates in pediatric PTSD. METHODS: Twenty-seven youths with PTSD and 21 nontraumatized typically developing (TD) youths were assessed at baseline and 1-year follow-up. At each visit, youths underwent structural magnetic resonance imaging and resting-state functional magnetic resonance imaging. Regions with volumetric abnormalities in whole-brain structural analyses were identified and used as seeds in exploratory intrinsic connectivity analyses. RESULTS: Youths with PTSD exhibited sustained reductions in gray matter volume (GMV) in right ventromedial prefrontal cortex (PFC) and bilateral ventrolateral PFC. Group-by-time analyses revealed aberrant longitudinal development in dorsolateral PFC, where typically developing youths exhibited normative decreases in GMV between baseline and follow-up, and youths with PTSD showed increases in GMV. Using these regions as seeds, patients with PTSD exhibited atypical longitudinal decreases in intrinsic PFC-amygdala and PFC-hippocampus connectivity, in contrast to increases in typically developing youths. Specifically, youths with PTSD showed decreasing ventromedial PFC-amygdala connectivity as well as decreasing ventrolateral PFC-hippocampus connectivity over time. Notably, volumetric abnormalities in ventromedial PFC and ventrolateral PFC were predictive of symptom severity. CONCLUSIONS: These findings represent novel longitudinal volumetric and connectivity changes in pediatric PTSD. Atypical prefrontal GMV and prefrontal-amygdala/hippocampus development may underlie persistence of PTSD in youths and could serve as future therapeutic targets.

Altered neural encoding of prediction errors in assault-related posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is widely associated with deficits in extinguishing learned fear responses, which relies on mechanisms of reinforcement learning (e.g., updating expectations based on prediction errors). However, the degree to which PTSD is associated with impairments in general reinforcement learning (i.e., outside of the context of fear stimuli) remains poorly understood. Here, we investigate brain and behavioral differences in general reinforcement learning between adult women with and without a current diagnosis of PTSD. 29 adult females (15 PTSD with exposure to assaultive violence, 14 controls) underwent a neutral reinforcement-learning task (i.e., two arm bandit task) during fMRI. We modeled participant behavior using different adaptations of the Rescorla-Wagner (RW) model and used Independent Component Analysis to identify timecourses for large-scale a priori brain networks. We found that an anticorrelated and risk sensitive RW model best fit participant behavior, with no differences in computational parameters between groups. Women in the PTSD group demonstrated significantly less neural encoding of prediction errors in both a ventral striatum/mPFC and anterior insula network compared to healthy controls. Weakened encoding of prediction errors in the ventral striatum/mPFC and anterior insula during a general reinforcement learning task, outside of the context of fear stimuli, suggests the possibility of a broader conceptualization of learning differences in PTSD than currently proposed in current neurocircuitry models of PTSD.