Search

Background: Pharmacologic treatment options for posttraumatic stress disorder (PTSD) are limited in number and effectiveness. Medications currently in use to treat PTSD were originally approved based on their efficacy in other disorders, such as major depr

Two open trials of Virtual Reality based exposure therapy (VRE) to desensitize Vietnam veterans with Posttraumatic Stress Disorder (PTSD) to some of their traumatic memories are described. A total of 21 patients were exposed to one of two virtual Vietnam computer-generated environments in which their individual traumatic experiences were simulated in response to their recounting these events. Although two patients experienced significant increases in symptoms during VRE, all patients' PTSD symptoms were below baseline by the 3-month posttreatment assessment. When the data from the two open trials was combined, clinically meaningful and statistically significant reductions in PTSD symptoms were found. These changes were long lasting as evidenced by the 6-month follow-up assessments. Two case examples are provided and future applications of this treatment are discussed. [ABSTRACT FROM AUTHOR]

The effectiveness of virtual reality (VR) as a behavioral intervention designed to decrease distress during port access procedure was examined in 20 7- to 14-year-old pediatric oncology patients. Children were randomized to either engage in an immersive VR environment during the procedure or to a no VR control condition. Children's distress was assessed through subjective self-ratings and objective physiological and behavioral ratings. Narrative accounts of the experience were used as a measure of how well the child coped with the procedure. VR was effective in reducing children's distress on all measures. Implications of these findings for intervention are discussed. [ABSTRACT FROM AUTHOR]

This study was an open-label, single-group, treatment-development project aimed at developing and testing a method for applying virtual reality exposure therapy (VRET) to active duty service members diagnosed with combat post-traumatic stress disorder (PTSD). Forty-two service members with PTSD were enrolled, and 20 participants completed treatment. The PTSD Checklist-Military version, Patient Health Questionnaire-9 for depression, and the Beck Anxiety Inventory were used as outcome measures. Of those who completed post-treatment assessment, 75% had experienced at least a 50% reduction in PTSD symptoms and no longer met DSM-IV criteria for PTSD at post treatment. Average PSTD scores decreased by 50.4%, depression scores by 46.6%, and anxiety scores by 36%. Intention-to-treat analyses showed that statistically significant improvements in PTSD, depression, and anxiety occurred over the course of treatment and were maintained at follow up. There were no adverse events associated with VRET treatment. This study provides preliminary support for the use of VRET in combat-related PTSD. Further study will be needed to determine the wider utility of the method and to determine if it offers advantages over other established PTSD treatment modalities. [ABSTRACT FROM AUTHOR]

3,4-methylenedioxymethamphetamine (MDMA) assisted therapy has been shown to be a safe and effective treatment for PTSD and emerging research suggests a change in personality traits may be a factor in treatment response. Most prior research on MDMA and personality has focused on cross-sectional comparisons of MDMA users and non-users; as such, well-controlled research assessing personality and affective states change following MDMA vs placebo administration is needed. In the current pre-registered study, we investigated the impact of MDMA administration on five-factor model (FFM) traits and affective states before and 48 h after drug administration in a randomized, placebo-controlled study of healthy adults ( N  = 34). Statistical significance was not observed for the four a priori hypotheses; however, medium effect sizes were found between MDMA administration and trait Openness and Positive Affect 48 h following drug administration, compared to placebo ( d  = .79 and .51, respectively). This study provides initial results to help guide future well-powered studies with large samples and longer follow-up timepoints to continue to investigate how MDMA impacts personality and emotional experience, which may inform optimization of MDMA treatment approaches.

At the 39th meeting of the International Society of Traumatic Stress Studies, three leading researchers and clinicians in technology-enabled traumatic stress support were invited to reflect on their careers and contributions to the field. Dr. Brian P. Marx has led the development of large-scale technologies to screen, assess, and treat traumatic stress pathology across diverse etiologies and needs. Dr. Barbara O. Rothbaum, a pioneer in the development of virtual reality for exposure therapy, has demonstrated the efficacy and scalability of digital treatment for traumatic stress. Retired Col. Dr. Eric Vermetten has worked extensively on the intersection of basic mechanisms, novel psychological and biological treatment, and technology for scalable assessment and treatment, primarily in military and mass casualty contexts. The panelists were asked to reflect on their initial ambitions, concerns, unexpected challenges, and the influence of their work on new research trajectories. Their insights provide valuable lessons about the process and content of their work, and their pioneering efforts have significantly advanced the field of technology-enabled traumatic stress support., (© 2024 International Society for Traumatic Stress Studies.)

Recent evidence supports the implementation of massed delivery of disorder-specific treatments in the military service member and veteran population. However, many treatment settings serve patients with a wide range of diagnoses, and often patients present with comorbid conditions. Growing evidence suggests transdiagnostic cognitive behavioral treatments are effective for a wide range of emotional disorders and may reduce barriers to access. Little is known about the feasibility and outcomes of the massed delivery of transdiagnostic treatments. The present study examined real-world outcomes of a 2-week intensive outpatient program using the Unified Protocol for emotional disorders (UP-IOP). The sample included military service members and veterans diagnosed with a range of emotional disorders, namely trauma- and stressor-related disorders, unipolar depressive disorders, and anxiety disorders. The present study examined outcomes of UP-IOP (depression, trauma-related symptom severity, and emotion dysregulation). Participants included all patients who sought UP-IOP in its first 15 months of operation ( N = 117). A diagnosis of posttraumatic stress disorder (PTSD) was an exclusion criterion because the site had an established PTSD-specific IOP treatment option. Findings indicate UP-IOP was feasible, had 94% patient retention, and was effective in reducing symptom severity (Cohen's d = 0.76 for depression symptom severity, Cohen's d = 0.80 for trauma-related symptom severity). There was no observed reduction in emotion dysregulation over the 2-week course of treatment. The intensive transdiagnostic approach resulted in effective symptom reduction in an accelerated timeframe while minimizing patient attrition. These findings indicate massed delivery of transdiagnostic cognitive behavioral therapy (CBT) treatments should continue to be explored, especially for this population. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: Despite considerable research examining the efficacy of psychedelic-assisted therapies (PATs) for treating psychiatric disorders, assessment of adverse events (AEs) in PAT research has lagged. Current AE reporting standards in PAT trials are poorly calibrated to features of PAT that distinguish it from other treatments, leaving many potential AEs unassessed., Methods: A multidisciplinary working group of experts involved in PAT pooled formally and informally documented AEs observed through research experience and published literature. This information was integrated with (a) current standards and practices for AE reporting in pharmacotherapy and psychotherapy trials and (b) published findings documenting post-acute dosing impacts of psychedelics on subjective states, meaning, and psychosocial health variables, to produce a set of AE constructs important to evaluate in PAT as well as recommended methods and time frames for their assessment and monitoring. Correspondence between identified potential AEs and current standards for AE assessment was examined, including the extent of coverage of identified AE constructs by 25 existing measures used in relevant research., Results: Fifty-four potential AE terms warranting systematized assessment in PAT were identified, defined, and categorized. Existing measures demonstrated substantial gaps in their coverage of identified AE constructs. Recommendations were developed for how to assess PAT AEs (including patient, clinician, and informant reports), and when to assess over preparation, dosing session, integration, and follow-up. Application of this framework is demonstrated in a preliminary assessment protocol (available in the supplement)., Conclusions: This assessment framework addresses the need to capture post-acute dosing AEs in PAT, accounting for its pharmacotherapy and psychotherapy components, as well as documented impacts of psychedelics on worldviews and spirituality., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Jessica L Maples-Keller has received research funding and consulting payments from COMPASS Pathways, and receives support from the Wounded Warrior Project (WWP), and Multidisciplinary Association of Psychedelic Studies. Barbara O Rothbaum has recently had funding from the Wounded Warrior Project, NIMH, National Science Foundation, and the Bob Woodruff Foundation. Barbara O Rothbaum receives royalties from Oxford University Press, Guilford, APPI, Psych Campus, and Emory University and received advisory board payments from Jazz Pharmaceuticals, Bioserenity, Cerebral Therapeutics, Otsuka, Psychwire, and Senseye. Barbara O Rothbaum owns equity in Virtually Better, Inc. that creates virtual environments. The terms of these arrangements have been reviewed and approved by Emory University in accordance with its conflict of interest policies. Boadie W Dunlop has received research support from Boehringer-Ingelheim, Compass Pathways, NIMH, and Usona, and has received consulting fees from Biohaven, The Department of Defense, Myriad Neuroscience, Otsuka, and Sage. Charles L Raison has received personal fees from Usona Institute and grants to Usona Institute from Dr. Bronner’s All-One, Fournier Family Foundation, Good Ventures, Steven and Alexandra Cohen Foundation, Tiny Blue Dot Foundation, Turnbull Family Foundation, William A Linton, Novartis, Sage/Biogen, Emory Healthcare, and Vail Health. Roman Palitsky, Deanna M Kaplan, John Perna, Zacchary Bosshardt, Holly F Levin-Aspenson, Ali John Zarrabi, Caroline Peacock, and George H Grant all report no disclosures. Tanja Mletzko reports no disclosures.

This brief review article will describe treatment approaches for posttraumatic stress disorder (PTSD) based on findings from basic research. The focus of this review will be fear conditioning and extinction models, which provide a translational model of PTSD that can help translate basic research in nonhuman animals through well-controlled trials confirming the efficacy of treatment approaches in humans with PTSD such as prolonged exposure therapy. Specific cognitive aspects of fear extinction processes, including consolidation and reconsolidation, are reviewed along with behavioral and pharmacological treatment strategies based on basic research in these areas including attempts to prevent the development of PTSD as well as the treatment of chronic PTSD. Pharmacological, behavioral, and device-based augmentation strategies of PTSD treatment based in basic science findings are reviewed, including those that disrupt noradrenergic receptor processes, medications that act on NMDA receptors, physical exercise, cannabinoids, estradiol, dexamethasone, yohimbine, losartan, dopamine, and MDMA, along with the evidence for their efficacy in human clinical samples. While fear extinction provides an exciting translational opportunity to improve PTSD based on basic science findings, we review limitations and challenges of the extant literature as well as future directions., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The Emory Healthcare Veterans Program (EHVP) is a multidisciplinary intensive outpatient treatment program for post-9/11 veterans and service members with invisible wounds, including posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), substance use disorders (SUD), and other anxiety- and depression-related disorders., Objective: This article reviews the EHVP., Methods: The different treatment tracks that provide integrated and comprehensive treatment are highlighted along with a review of the standard, adjunctive, and auxiliary services that complement individualized treatment plans., Results: This review particularly emphasizes the adjunctive neurorehabilitation service offered to veterans and service members with a TBI history and the EVHP data that indicate large reductions in PTSD and depression symptoms across treatment tracks that are maintained across 12 months follow up. Finally, there is a discussion of possible suboptimal treatment response and the pilot programs related to different treatment augmentation strategies being deploying to ensure optimal treatment response for all., Conclusion: Published data indicate that the two-week intensive outpatient program is an effective treatment program for a variety of complex presentations of PTSD, TBI, SUD, and other anxiety- and depression-related disorders in veterans and active duty service members.

Objective: Substance use disorders (SUDs) and posttraumatic stress disorder (PTSD) are costly and highly co-occurring diagnoses, particularly among veterans, suggesting a need to understand this comorbidity and effectively treat both disorders among this population., Methods: The current study aimed to examine substance use outcomes among post-9/11 veterans and service members ( N  = 48) who completed a two-week intensive outpatient program with concurrent treatment for and PTSD using Prolonged Exposure and substance use. Substance use was assessed at two weeks and three months posttreatment., Results: The intensive program had high completion rates and demonstrated decreases in substance use at two weeks and three months posttreatment. Additionally, lower PTSD symptoms at treatment completion were related to less substance use posttreatment., Conclusions: Concurrent intensive treatment of PTSD and SUDs can lead to symptom improvement in a short period of time. Findings support the self-medication model, such that PTSD symptoms at treatment completion were related to substance use at follow-up.

Introduction: Individuals living in areas with high rates of poverty are disproportionately affected by posttraumatic stress disorder (PTSD). Despite this association, little is known about how neighborhood poverty rates impact risk for PTSD development. In the current prospective study, we determined the relationship between neighborhood poverty rate and PTSD symptoms six-months after experiencing a traumatic event in a sample of varied race, gender, and socioeconomic status., Methods: Participants ( N =252) were enrolled in a hospital emergency department after experiencing a traumatic event. Demographic information (including zip code of residence), baseline PTSD symptoms, and baseline trauma history was assessed in the emergency department. PTSD symptoms were again assessed six-months post-trauma. Neighborhood poverty rate was determined using the American Community Survey., Results: Correlation analyses revealed that neighborhood poverty was significantly associated with baseline PTSD symptoms ( r= .181, p= .004) and PTSD symptoms six-months post-trauma ( r= .163, p= .009). A regression analysis controlling for baseline trauma exposure, clinician-rated trauma severity, and individual socioeconomic status demonstrated that neighborhood poverty predicted PTSD symptoms six-months post-trauma (R 2 = 0.099, B = 0.15, p= 0.04), but this relationship was no longer significant when baseline PTSD symptoms was added as an additional covariate (R 2 =.304, B = 0.07, p> 0.05)., Conclusion: Overall, results suggest that neighborhood poverty generally increases PTSD symptom severity, and the context in which an individual lives should be considered when conceptualizing risk for PTSD.

Emotional engagement is necessary for successful exposure therapy for posttraumatic stress disorder (PTSD), but dissociation is considered a barrier to emotional engagement. Virtual reality exposure therapy (VRE) uses multi-sensory virtual environments to increase emotional engagement during exposure therapy, and average treatment outcomes are comparable to traditional exposure therapy. However, individual factors (e.g., depression) can predict differential responses to VRE. Studies have yet to investigate whether VRE would be more effective in treating patients with dissociation compared to traditional PE. This secondary analysis of a randomized clinical trial explores whether dissociation predicts treatment outcomes to exposure therapy among active-duty soldiers (N = 108) diagnosed with PTSD. We also examine whether individuals reporting dissociative symptoms demonstrated differential treatment responses to VRE and PE. Results indicated a significant two-way interaction between dissociation and time in treatment, such that dissociation blunted the negative relationship between time and PTSD symptoms. Dissociation was not associated with treatment session attendance or drop out. Results also revealed no significant effect of treatment group (PE or VRE) on the relationship between dissociation and PTSD symptoms. Findings contribute to a body of literature supporting the potential clinical and research utility of a dissociative subtype of PTSD., Competing Interests: Declaration of competing interest We have no known conflicts of interest to disclose., (Published by Elsevier Ltd.)

Objective: Predicting risk of posttraumatic stress disorder (PTSD) in the acute care setting is challenging given the pace and acute care demands in the emergency department (ED) and the infeasibility of using time-consuming assessments. Currently, no accurate brief screening for long-term PTSD risk is routinely used in the ED. One instrument widely used in the ED is the 27-item Immediate Stress Reaction Checklist (ISRC). The aim of this study was to develop a short screener using a machine learning approach and to investigate whether accurate PTSD prediction in the ED can be achieved with substantially fewer items than the IRSC., Method: This prospective longitudinal cohort study examined the development and validation of a brief screening instrument in two independent samples, a model development sample (N = 253) and an external validation sample (N = 93). We used a feature selection algorithm to identify a minimal subset of features of the ISRC and tested this subset in a predictive model to investigate if we can accurately predict long-term PTSD outcomes., Results: We were able to identify a reduced subset of 5 highly predictive features of the ISRC in the model development sample (AUC = 0.80), and we were able to validate those findings in the external validation sample (AUC = 0.84) to discriminate non-remitting vs. resilient trajectories., Conclusion: This study developed and validated a brief 5-item screener in the ED setting, which may help to improve the diagnostic process of PTSD in the acute care setting and help ED clinicians plan follow-up care when patients are still in contact with the healthcare system. This could reduce the burden on patients and decrease the risk of chronic PTSD., (Copyright © 2023. Published by Elsevier Inc.)

Background: Sexual assault and rape are the traumatic life events with the highest probability for posttraumatic stress disorder (PTSD), which can have devastating consequences for those afflicted by the condition. Studies indicate that modified prolonged exposure (mPE) therapy may be effective in preventing the development of PTSD in recently traumatized individuals, and especially for people who have experienced sexual assault. If a brief, manualized early intervention can prevent or reduce post-traumatic symptoms in women who have recently experienced rape, healthcare services targeted for these populations (i.e., sexual assault centers, SACs) should consider implementing such interventions as part of routine care., Methods/design: This is a multicenter randomized controlled add-on superiority trial that enrolls patients attending sexual assault centers within 72 h after rape or attempted rape. The objective is to assess whether mPE shortly after rape can prevent the development of post-traumatic stress symptoms. Patients will be randomized to either mPE plus treatment as usual (TAU) or TAU alone. The primary outcome is the development of post-traumatic stress symptoms 3 months after trauma. Secondary outcomes will be symptoms of depression, sleep difficulties, pelvic floor hyperactivity, and sexual dysfunction. The first 22 subjects will constitute an internal pilot trial to test acceptance of the intervention and feasibility of the assessment battery., Discussion: This study will guide further research and clinical initiatives for implementing strategies for preventing post-traumatic stress symptoms after rape and provide new knowledge about which women may benefit the most from such initiatives and for revising existing treatment guidelines within this area., Trial Registration: ClinicalTrials.gov NCT05489133. Registered on 3 August 2022., (© 2023. The Author(s).)

Introduction: The Emory University Prolonged Exposure (PE) Consultant Training Program seeks to develop a national network of competent PE consultants. Comprehensive training in empirically supported treatment (EST), such as PE, includes a didactic training followed by a period of experiential learning through consultation during real-world clinical practice (Karlin & Cross, 2014). Expert consultants are needed to meet demand as ESTs are disseminated., Method: The Emory program has developed a training model to develop 18 consultation skills within five competency domains: the consultation relationship, general psychotherapy skills, PE-specific skills, trainee barriers to delivery, and implementation., Results: The current article outlines these domains and discusses their theoretical background and applied value for PE consultant training, drawing on examples from the Emory program., Discussion: Just as manualizing therapy has allowed for EST dissemination, the operationalizing of consultation competencies can provide a first step in disseminating evidence-based consultation practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is common following sexual assault and associated with more severe symptomology and increased likelihood of sexual revictimization. Integrated interventions aimed at reducing PTSD and AUD symptoms following recent sexual assault are needed and should address barriers to care and early treatment termination. The proposed study will test a novel, brief (5 to 7 sessions) intervention that integrates Written Exposure Therapy for PTSD and Cognitive Behavioral Therapy for AUD, and is initiated within the first six weeks post-assault. In Phase 1, qualitative analysis of content gathered during focus groups with treatment providers will be conducted to inform intervention development. In Phase 2, a proof-of-concept pilot study (n = 10) of the intervention, Substance Use Skills Training and Exposure Post-Sexual Assault (STEPS), will be conducted. In Phase 3, a pilot randomized controlled trial (RCT) among 54 recent sexual assault survivors will be implemented using the updated manualized STEPS intervention to evaluate feasibility and preliminary efficacy in reducing PTSD and AUD symptoms. Ecological momentary assessments will be used to assess daily alcohol use, craving, affect, intrusions and avoidance. The effects of STEPS on commonly associated symptoms (e.g., depression, substance use) will be examined. The proposed study has the potential to make a significant public health impact by advancing knowledge on the link between sexual assault and co-occurring PTSD and AUD and informing early intervention efforts for this high-risk population., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Brian Marx receives royalties from the American Psychological Association for publishing the Written Exposure Therapy manual., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The focus of this chapter is an overview of integrating virtual reality (VR) technology within the context of exposure therapy for anxiety disorders, a gold standard treatment, with a focus on how VR can help facilitate extinction learning processes integral to these interventions. The chapter will include an overview of advantages of incorporating VR within exposure therapy, and benefits specifically within an inhibitory learning approach for extinction training. A review of the empirical literature on the effectiveness of VR exposure therapy for specific phobia and PTSD will be provided, as well as practical overview of how to effectively incorporate VR within exposure therapy., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Posttraumatic stress disorder (PTSD) is a heritable (h 2  = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10 -8 ). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further., (© 2022. The Author(s).)

Female individuals are more likely to be diagnosed with PTSD following trauma exposure than males, potentially due, in part, to underlying neurobiological factors. Several brain regions underlying fear learning and expression have previously been associated with PTSD, with the hippocampus, amygdala, dorsal anterior cingulate cortex (dACC), and rostral ACC (rACC) showing altered volume and function in those with PTSD. However, few studies have examined how sex impacts the predictive value of subcortical volumes and cortical thickness in longitudinal PTSD studies. As part of an emergency department study completed at the Grady Trauma Project in Atlanta, GA, N = 93 (40 Female) participants were enrolled within 24 h following a traumatic event. Multi-echo T1-weighted MRI images were collected one-month post-trauma exposure. Bilateral amygdala and hippocampal volumes and rACC and dACC cortical thickness were segmented. To assess the longitudinal course of PTSD, the PTSD Symptom Scale (PSS) was collected 6 months post-trauma. We investigated whether regional volume/thickness interacted with sex to predict later PTSD symptom severity, controlling for PSS score at time of scan, age, race, and trauma type, as well as intracranial volume (ICV) for subcortical volumes. There was a significant interaction between sex and rACC for 6-month PSS, such that right rACC thickness was positively correlated with 6-month PSS scores in females, but not in males. In examining PTSD symptom subtypes and depression symptoms, greater rACC thickness in females predicted greater avoidance symptoms, while smaller rACC thickness in males predicted greater depression symptoms. Amygdala and hippocampus volume and dACC thickness showed no main effect or interaction with sex. The current findings provide evidence for sex-based differences in how brain volume predicts future PTSD severity and symptoms and supports the rACC as being a vital region regarding PTSD. Gender differences should be assessed in future longitudinal PTSD MRI studies for more accurate identification of future PTSD risk following trauma., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Background: Scant research has focused on posttraumatic stress disorder (PTSD) in the SCI population, despite high prevalence estimates. Fortunately, prolonged exposure therapy (PE) is a well-researched and highly effective treatment for PTSD. Our recent clinical trial showed that standard 12-session PE was effective for PTSD treatment among inpatients with SCI. Early intervention with brief PE (3-sessions) delivered in the emergency department has also been effective for PTSD prevention, but has not been tested among people post-SCI. Thus, we aim to conduct the first test of the Brief PE intervention to prevent PTSD among patients with SCI., Methods: Adults who have experienced a SCI (N = 200) will be randomly assigned during inpatient rehabilitation to either: (a) 3 60-min sessions of Brief PE (intervention group) or (b) treatment as usual (control group)., Results: The primary outcome measure (PTSD symptoms measured by the PSSI-5) and secondary outcome measures (depression, anxiety, pain, quality of life, sleep disturbance, and resilience) will be assessed at baseline, 1-month, 3-months, and 6-months. Hierarchical linear modeling (HLM) will be used to evaluate the effectiveness of the PE intervention on PTSD and secondary outcomes. Descriptive statistics will examine feasibility and will include the number of participants enrolled, the number of sessions completed, fidelity of Brief PE delivery, and average scores for difficulty and helpfulness of the intervention scales for those randomized to intervention., Conclusions: Successful completion of this study will provide an evidence-based program to alleviate posttraumatic distress post spinal cord injury and prevent long-term development of PTSD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc.)

Objective: Post-9/11 U.S. veterans and servicemembers are at increased risk for suicide, indicating an important need to identify and mitigate suicidal ideation and behaviors in this population., Method: Using data modeling techniques, we examined correlates of suicidal ideation and behavior at intake in 261 Post-9/11 veterans and servicemembers seeking mental health treatment., Results: Our sample endorsed high rates of suicidal ideation and behavior. Approximately 40% of our sample scored in a range on the Suicide Behaviors Questionnaire-Revised (SBQ-R), indicating high clinical risk for suicide. Results from multivariate analyses indicate that greater state and/or trait depression severity, greater anger and anger expression, less impulse control, and lower rank were consistently associated with suicidal ideation and behavior across our models. Negative posttraumatic thoughts about the self, gender, and military branch of service were also significantly associated with suicidal ideation and behavior., Conclusions: Suicidal ideation and behaviors are common in veterans seeking mental health treatment. State and/or trait depression, anger and impulse control were predictors of increased risk for suicidal ideation and behavior across models. Consistencies and differences across models as well as limitations and practical implications for the findings are discussed., (Published by Elsevier Ltd.)

Empirically-supported psychotherapies for posttraumatic stress disorder (PTSD) are highly effective and recommended as first-line treatments, yet dropout rates from standard outpatient therapy are high. Intensive outpatient programs (IOPs) that provide these therapies in condensed format with complementary interventions show promise, as they have demonstrated similar efficacy and higher retention rates. The current study examined initial and long-term outcomes up to 12-months following a 2-week PTSD IOP involving daily prolonged exposure therapy (PE) and adjunctive interventions for veterans and military service members. Participants (N = 376) demonstrated high retention (91%) and large effect size reductions in self-reported PTSD and depression symptoms after two weeks. Small increases in symptoms occurred after 3 months but these stabilized and large reductions compared to baseline were maintained up to 12 months. Piecewise multilevel modeling indicated that demographic variables did not predict PTSD or depression symptom trajectories. Higher PTSD and depression severity at intake predicted higher symptomatology across timepoints and larger relative gains during treatment. Greater alcohol use prior to treatment was associated with higher PTSD symptomatology but did not affect the magnitude of gains. A history of childhood sexual abuse was associated with greater reduction in depression symptoms over treatment, although this effect faded over follow-up. Together these findings underscore the long-term effectiveness of a PE-based IOP across a diverse range of veterans and service members., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Posttraumatic stress disorder (PTSD) is a significant public health issue. Yet, there are limited treatment options and no data to suggest which treatment will work for whom. We tested the efficacy of virtual reality exposure (VRE) or prolonged imaginal exposure (PE), augmented with D-cycloserine (DCS) for combat-related PTSD. As an exploratory aim, we examined whether brain-derived neurotrophic factor (BDNF) and fatty acid amide hydrolase (FAAH) moderated treatment response. Military personnel with PTSD (n = 192) were recruited into a multisite double-blind randomized controlled trial to receive nine weeks of VRE or PE, with DCS or placebo. Primary outcome was the improvement in symptom severity. Randomization was stratified by comorbid depression (MDD) and site. Participants in both VRE and PE showed similar meaningful clinical improvement with no difference between the treatment groups. A significant interaction (p = 0.45) suggested VRE was more effective for depressed participants (CAPS difference M = 3.51 [95% CI 1.17-5.86], p = 0.004, ES = 0.14) while PE was more effective for nondepressed participants (M = -8.87 [95% CI -11.33 to -6.40], p < 0.001, ES = -0.44). The main effect of DCS vs. placebo was not significant. Augmentation by MDD interaction (p = 0.073) suggested that depressed participants improved more on placebo (M = -8.43 [95% CI -10.98 to -5.88], p < 0.001, ES = -0.42); DCS and placebo were equally effective for nondepressed participants. There was an apparent moderating effect of BDNF Val66Met polymorphism on DCS augmentation (ES = 0.67). Met66 allele carriers improved more on DCS (ES = -0.25). FAAH 385 A carriers improved more than non-carriers (ES = 0.33), particularly those with MDD (ES = 0.62). This study provides a step toward precision therapeutics for PTSD by demonstrating that comorbid MDD and genetic markers may help guide treatment selection.ClinicalTrials.gov Identifier: NCT01352637., (© 2022. The Author(s).)

Objective: Advocates of massed prolonged exposure (PE) argue an intensive approach may address between-session distraction, avoidance, and demotivation that can result in dropout or interference with treatment engagement. Despite growing empirical support for the efficacy and effectiveness of massed PE, little evidence suggests massed PE matches patient preferences. Further, program evaluation efforts have not assessed unforeseen or underestimated benefits and drawbacks of massed PE. The current study is the first known study to assess patient reactions to massed PE., Method: Participants were 25 military veterans diagnosed with posttraumatic stress disorder who were accepted into a 2-week massed PE program. After the final session, participants completed a written survey using open-ended questions regarding their perceived benefits and drawbacks of massing the full PE protocol into 2 weeks. After demonstrating interrater reliability, coders used a thematic analysis approach to identify themes and subthemes in the qualitative data., Results: Overall, participant reactions were much more positive (51.27%) than negative (17.77%). Participants identified benefits that are largely consistent with the justification for massed PE: (a) The structure limits distractions and avoidance, and (b) quick gains enhance motivation and engagement. With respect to drawbacks, participants identified that massed PE causes short-term discomfort and is demanding in terms of effort and time, which is also consistent with clinical theory of PE and justification for massed delivery., Conclusions: Participant reactions correspond to the rationale for massed PE; that is, participants identified that despite short-term discomfort and demands, they tend to like and benefit from the intensity of massed PE. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A key feature of posttraumatic stress disorder (PTSD) is a disruption of hypothalamic-pituitary-adrenal (HPA) axis feedback sensitivity and cortisol levels. Despite known diurnal rhythmicity of cortisol, there has been little exploration of the circadian timing of the index trauma and consequent cortisol release. Stress-related glucocorticoid pulses have been shown to shift clocks in peripheral organs but not the suprachiasmatic nucleus, uncoupling the central and peripheral clocks. A sample of 425 participants was recruited in the Emergency Department following a DSM-IV-TR Criterion A trauma. The Zeitgeber time of the trauma was indexed in minutes since sunrise, which was hypothesized to covary with circadian blood cortisol levels (high around sunrise and decreasing over the day). Blood samples were collected M(SD)= 4.0(4.0) hours post-trauma. PTSD symptoms six months post-trauma were found to be negatively correlated with trauma time since sunrise (r(233) = -0.15, p = 0.02). The effect remained when adjusting for sex, age, race, clinician-rated severity, education, pre-trauma PTSD symptoms, and time of the blood draw (β = -0.21, p = 0.00057). Cortisol levels did not correlate with blood draw time, consistent with a masking effect of the acute stress response obscuring the underlying circadian rhythm. Interactions between trauma time and expression of NPAS2 (p unadjusted =0.042) and TIMELESS (p unadjusted =0.029) predicted six-month PTSD symptoms. The interaction of trauma time and cortisol concentration was significantly correlated with the expression of PER1 (p adjusted =0.029). The differential effect of time of day on future symptom severity suggests a role of circadian effects in PTSD development, potentially through peripheral clock disruption., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Prolonged exposure (PE) therapy is a first-line treatment for posttraumatic stress disorder (PTSD) and involves repeated presentation of trauma-related cues without aversive outcomes. A primary learning mechanism of PE is fear extinction (new learning that a dangerous cue is now safe) and its retention (maintaining this new learning over time). Extant research suggests extinction is impaired in PTSD patients. In this study, we employed an established fear-potentiated startle-based paradigm to examine fear acquisition, extinction learning and retention before and after completion of intensive outpatient treatment. First, PTSD patients undergoing PE (n = 55) were compared to trauma-exposed patients without PTSD (n = 57). We identified excessive fear in PTSD patients during acquisition and extinction before treatment compared to non-PTSD patients. At post-treatment, we examined the return of fear after extinction in PTSD patients showing high or low treatment response to PE (≥50% change in PTSD symptom severity vs. < 50%). High PE responders maintained fear extinction learning whereas low PE responders showed significant return of fear at post-treatment. These results replicate and extend previous findings of impaired extinction in PTSD and provide support for the proposed theoretical link between fear extinction and PE response., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Inhibition is a critical executive control process and an established neurobiological phenotype of PTSD, yet to our knowledge, no prospective studies have examined this using a contextual cue task that enables measurement of behavioural response and neural activation patterns across proactive and reactive inhibition., Objective: The current longitudinal study utilised functional magnetic resonance imaging (fMRI) to examine whether deficits in proactive and reactive inhibition predicted PTSD symptoms six months after trauma., Method: Twenty-three (65% males) medical patients receiving emergency medical care from a level 1 trauma centre were enrolled in the study and invited for an MRI scan 1-2-months post-trauma. PTSD symptoms were measured using self-report at scan and 6-months post-trauma. A stop-signal anticipation task (SSAT) during an fMRI scan was used to test whether impaired behavioural proactive and reactive inhibition, and reduced activation in right inferior frontal gyrus (rIFG), ventromedial prefrontal cortex (vmPFC), and bilateral hippocampus, were related to PTSD symptoms. We predicted that lower activation levels of vmPFC and rIFG during reactive inhibition and lower activation of hippocampus and rIFG during proactive inhibition would relate to higher 6-month PTSD symptoms., Results: No significant associations were found between behavioural measures and 6-month PTSD. Separate linear regression analyses showed that reduced rIFG activation ( F 1,21  =  9.97, R 2  =  .32 , p =  .005) and reduced vmPFC activation ( F 1,21  =  5.19, R 2  =  .20, p =  .03) significantly predicted greater 6-month PTSD symptoms; this result held for rIFG activation controlling for demographic variables and baseline PTSD symptoms (β = -.45, p =  .04) and Bonferroni correction., Conclusion: Our findings suggest that impaired rIFG and, to a lesser extent, vmPFC activation during response inhibition may predict the development of PTSD symptoms following acute trauma exposure. Given the small sample size, future replication studies are needed., Highlights: Impaired inhibition may be an important risk factor for the development of PTSD following trauma, with less right inferior frontal gyrus and ventromedial prefrontal cortex activation during response inhibition predicting PTSD development., Competing Interests: Dr. Ressler has received consulting income from Alkermes, research support from NIH, Genomind, and Brainsway, and he is on scientific advisory boards for Janssen and Verily, all of which is unrelated to the present work. Dr. Rothbaum is a consultant to and owns equity in Virtually Better, Inc. that creates virtual environments. The terms of these arrangements have been reviewed and approved by Emory University in accordance with its conflict of interest policies, and is unrelated to the present work. Other authors report no potential conflicts of interest., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Intensive outpatient programs (IOPs) for trauma-focused therapy, such as prolonged exposure (PE), have the potential to deliver highly effective treatment, quickly and with minimal dropout. Identifying factors that predict maintenance of gains after treatment can help triage individuals who may need additional services., Methods: Growth mixture modeling (GMM) was used to identify classes of posttraumatic stress disorder (PTSD) and depression symptom trajectories across the year following a 2-week IOP, delivering daily PE for PTSD for post-9/11 Veterans. Predictors of trajectories were examined., Results: Three classes of trajectories best-fit the data for PTSD and depression symptoms. Two classes made up the majority of the sample (85%) and both maintained significantly reduced PTSD symptoms across the year following therapy. For a minority of the sample (14.6%), PTSD symptoms rebounded after treatment. These individuals were highly likely to be categorized in the persistent depression class., Conclusions: IOP-delivered PE is effective, and gains are largely maintained. The minority of patients who do not maintain their gains as robustly are likely to report persistent depressive symptoms in treatment and higher PTSD symptoms on a self-report measure., (© 2022 Wiley Periodicals LLC.)

Background: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs)., Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms., Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program., Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods., (Copyright © 2021 Society of Biological Psychiatry. All rights reserved.)

Posttraumatic negative thoughts about one's self and the world are related to posttraumatic stress disorder (PTSD) symptom severity and change in cognitive behavioral treatment (CBT), but little is known about this association when CBT is delivered with medication. The current study presents a planned comparison of changes in negative posttraumatic thoughts during (a) prolonged exposure (PE) plus pill placebo (PE+PLB), (b) sertraline plus enhanced medication management (SERT+EMM), and (c) PE plus sertraline (PE+SERT) as part of a randomized clinical trial in a sample of 176 veterans. Lagged regression modeling revealed that change in posttraumatic negative thoughts was associated with PTSD symptom change in the conditions in which participants received sertraline, ds = 0.14-0.25, ps = 0.04-.001). However, contrary to previous research, the models that started with symptom change were also statistically significant, d = 0.23, p < .001, for the lagged effect of symptoms on negative thoughts about self in the SERT+EMM condition, indicating a bidirectional association between such thoughts and PTSD symptoms. In the PE+PLB condition, no significant association between posttraumatic thoughts and PTSD symptoms emerged in either direction. These results suggest that the previously demonstrated role of change in posttraumatic thoughts leading to PTSD symptom reduction in PE may be altered when combined with pill administration, either active or placebo., (© 2021 International Society for Traumatic Stress Studies.)

While inflammatory markers have been implicated in the link between PTSD and poor health outcomes, there is a paucity of research investigating C-reactive protein (CRP) and psychotherapy treatment response for posttraumatic stress disorder (PTSD). The present study utilized a large, well-characterized sample of veterans and service members (N = 493) engaged in intensive psychotherapy to investigate the associations between CRP, trauma exposure, related variables, and PTSD and depression, as well as investigating if CRP was associated with PTSD psychotherapy treatment response. Bivariate correlation results indicate that CRP was significantly associated with BMI (r = 0.48) and severity of experiences of childhood physical and sexual abuse (r = 0.14 and 0.15, respectively) and was not significantly associated with baseline PTSD total symptom severity, PTSD symptom clusters, or depression symptom severity (rs ranging from -0.03 to 0.04). In multivariate regression models investigating if CRP and related variables were associated with PTSD baseline symptom severity, CRP was not a significant predictor (β = -0.03). Hierarchical linear modeling did not identify CRP as a significant predictor of PTSD psychotherapy outcome. Given that findings indicate that CRP was broadly elevated in this treatment seeking sample but not associated with PTSD and depression symptom severity, results suggest CRP may not be a specific biomarker for PTSD or depression but may be elevated in psychiatric disease more generally., (Copyright © 2021. Published by Elsevier Inc.)

Background: Fear conditioning and extinction are well-characterized cross-species models of fear-related posttraumatic stress disorder (PTSD) symptoms, and recent animal data suggest that 3,4-methylenedioxymethamphetamine (MDMA) enhances fear extinction retention., Aims: This study investigated the effect of MDMA on fear learning, extinction training, and retention in healthy humans., Methods: The study involved a randomized placebo-controlled, two-group, parallel design trial in a sample of healthy adults, age 21-55 recruited from a major metropolitan area. The experimental paradigm included a fear acquisition session followed by an extinction training session 24 hours later, and 2 hours after study drug administration. Fear extinction retention was measured 48 hours after extinction training. Participants ( N  = 34; 70.6% male and 29.4% female) were randomly assigned in 1:1 ratio to 100 mg MDMA or placebo. All randomized participants completed the trial and were included in primary analyses. Safety was monitored via adverse events and vital signs. MDMA was well-tolerated with no serious adverse events., Results: Results indicated a significant main effect of session between extinction training and retention with no significant group differences. Significantly more participants in the MDMA group retained extinction learning compared to the placebo group (χ 2  = 7.29, p  = 0.007)., Conclusion: Although we did not observe the hypothesized facilitation of extinction retention, the findings from this initial human trial provide compelling rationale to continue to explore the potential for MDMA to impact extinction retention.Clinical Trials Registry Name and Identifier: Evaluation of MDMA on Startle Response (NCT0318176) https://clinicaltrials.gov/ct2/show/NCT03181763?term = MDMA&draw = 2&rank = 9.

Objective: The impact of disrupted sleep on the effectiveness of prolonged exposure (PE) therapy for posttraumatic stress disorder (PTSD) is not well understood. Researchers have suggested that comorbid sleep disorders contribute to nonresponse by impairing therapeutic mechanisms such as emotional processing of trauma memories and extinction in cued fear conditioning. Several studies indicate daytime sleepiness, insomnia, and nightmares are correlated with PTSD symptom severity. However, a recent randomized controlled trial found that these sleep disorder symptoms did not affect PTSD symptom change over the course of massed PE (i.e., daily sessions across 2 weeks)., Method: The current study used an ecologically valid clinical sample to examine whether daytime sleepiness, insomnia, and nightmares interfere with the slope of symptom change in massed PE., Results: Results indicate that all 3 sleep disorder symptoms correlate with PTSD symptom severity on the first day of treatment but were not associated with symptom change., Conclusions: These findings are consistent with the expectation that the daily structure of massed PE may enhance treatment engagement in patients who are typically drowsy or not well-rested, thus facilitating fear extinction. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Although aspects of brain morphology have been associated with chronic posttraumatic stress disorder (PTSD), limited work has investigated multimodal patterns in brain morphology that are linked to acute posttraumatic stress severity. In the present study, we utilized multimodal magnetic resonance imaging to investigate if structural covariance networks (SCNs) assessed acutely following trauma were linked to acute posttraumatic stress severity., Methods: Structural magnetic resonance imaging data were collected around 1 month after civilian trauma exposure in 78 participants. Multimodal magnetic resonance imaging data fusion was completed to identify combinations of SCNs, termed structural covariance profiles (SCPs), related to acute posttraumatic stress severity collected at 1 month. Analyses assessed the relationship between participant SCP loadings, acute posttraumatic stress severity, the change in posttraumatic stress severity from 1 to 12 months, and depressive symptoms., Results: We identified an SCP that reflected greater gray matter properties of the anterior temporal lobe, fusiform face area, and visual cortex (i.e., the ventral visual stream) that varied curvilinearly with acute posttraumatic stress severity and the change in PTSD symptom severity from 1 to 12 months. The SCP was not associated with depressive symptoms., Conclusions: We identified combinations of multimodal SCNs that are related to variability in PTSD symptoms in the early aftermath of trauma. The identified SCNs may reflect patterns of neuroanatomical organization that provide unique insight into acute posttraumatic stress. Furthermore, these multimodal SCNs may be potential candidates for neural markers of susceptibility to both acute posttraumatic stress and the future development of PTSD., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Many reports have documented the relationship between post-traumatic stress disorder (PTSD) and substance use. Substance use is commonly comorbid with PTSD and is a risk factor for trauma exposure. The aim of this study was to prospectively examine how recent substance use, abuse, or dependence influenced the development of PTSD in the context of a prior trauma history, including child abuse, and the severity of initial trauma reactions. Participants (N = 81) were recruited and assessed at the emergency department of a large urban hospital in Miami and serum levels of common drugs of abuse were measured. Although substance use appeared to be a risk factor for trauma exposure, neither self-reported nor blood toxicology influenced the development of PTSD. Positive toxicology screens were more likely to be associated with a diagnosis of substance abuse or dependence, χ 2 (1) = 4.11, p = .04. Participants with a history of physical abuse were more likely to have a positive toxicology screen, χ 2 (1) = 4.03, p = .05. The majority of our trauma-exposed subjects (66%) were found to be positive for one or more illicit substances at presentation at the ED. The current findings provide support for the "high risk" hypothesis in which substance use is associated with increased trauma exposure., (Copyright © 2021. Published by Elsevier Ltd.)

High rates of drop-out from treatment of PTSD have challenged implementation. Care models that integrate PTSD focused psychotherapy and complementary interventions may provide benefit in retention and outcome. The first 80 veterans with chronic PTSD enrolled in a 2-week intensive outpatient program combining Prolonged Exposure (PE) and complementary interventions completed symptom and biological measures at baseline and posttreatment. We examined trajectories of symptom change, mediating and moderating effects of a range of patient characteristics. Of the 80 veterans, 77 completed (96.3%) treatment and pre- and posttreatment measures. Self-reported PTSD (p < .001), depression (p < .001) and neurological symptoms (p < .001) showed large reductions with treatment. For PTSD, 77% (n = 59) showed clinically significant reductions. Satisfaction with social function (p < .001) significantly increased. Black veterans and those with a primary military sexual trauma (MST) reported higher baseline severity than white or primary combat trauma veterans respectively but did not differ in their trajectories of treatment change. Greater cortisol response to the trauma potentiated startle paradigm at baseline predicted smaller reductions in PTSD over treatment while greater reductions in this response from baseline to post were associated with better outcomes. Intensive outpatient prolonged exposure combined with complementary interventions shows excellent retention and large, clinically significant reduction in PTSD and related symptoms in two weeks. This model of care is robust to complex presentations of patients with varying demographics and symptom presentations at baseline. (PsycInfo Database Record (c) 2021 APA, all rights reserved).