Unraveling PTSD: Symptom cluster change during and 1 year after veterans' residential PTSD treatment.

OBJECTIVE: Although treatment of posttraumatic stress disorder (PTSD) is effective in reducing symptom severity, remission rates are low. One potential underlying reason for treatment ineffectiveness is differential response of specific PTSD symptom clusters. Using data from a national Veterans Affairs (VA) residential PTSD treatment cohort, we conducted a longitudinal study to examine changes in Diagnostic and Statistical Manual of Mental Disorders, fifth edition PTSD symptom clusters from admission to 1-year follow-up. METHOD: PTSD symptom data were analyzed from a national cohort of veterans who completed VA PTSD residential treatment between October 2019 and September 2020 (n = 1,648; 13% women; median age 44.2 years). Endorsement (%) and severity (M[SD]) of PTSD clusters and individual symptoms were compared at admission, discharge, 4-month and 1-year follow-ups. RESULTS: Large magnitude reductions in all four PTSD symptom clusters were observed from admission to discharge and both follow-ups; however, endorsement of all symptom clusters remained high. Intrusions (Cluster B) were the most highly endorsed at discharge and follow-up, whereas avoidance symptoms (Cluster C) were the least highly endorsed. Differential patterns of change were observed among the 20 individual PTSD symptoms; for example, flashbacks decreased during treatment, but increased to near admission levels by 1-year postdischarge. CONCLUSIONS: Results suggest that intrusive symptoms may be more resistant to residential treatment for PTSD and contribute to lower likelihood of treatment success. Future work is needed to examine differential treatment response for PTSD clusters, to inform the improvement of current and creation of novel treatment interventions, and to better address intrusive symptoms to maximize PTSD treatment gains. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Emotional State Transitions in Trauma-Exposed Individuals With and Without Posttraumatic Stress Disorder.

Importance: Posttraumatic stress disorder (PTSD) is marked by the contrasting symptoms of hyperemotional reactivity and emotional numbing (ie, reduced emotional reactivity). Comprehending the mechanism that governs the transition between neutral and negative emotional states is crucial for developing targeted therapeutic strategies. Objectives: To explore whether individuals with PTSD experience a more pronounced shift between neutral and negative emotional states and how the intensity of emotional numbing symptoms impacts this shift. Design, Setting, and Participants: This cross-sectional study used hierarchical bayesian modeling to fit a 5-parameter logistic regression to analyze the valence ratings of images. The aim was to compare the curve's slope between groups and explore its association with the severity of emotional numbing symptoms. The study was conducted online, using 35 images with a valence range from highly negative to neutral. The rating of these images was used to assess the emotional responses of the participants. The study recruited trauma-exposed individuals (witnessed or experienced life-threatening incident, violent assault, or someone being killed) between January 17 and March 8, 2023. Participants completed the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) (PCL-5). Exposure: On the basis of DSM-5 criteria (endorsing at least 1 symptom from clusters B and C and 2 from D and E), participants were categorized as having probable PTSD (pPTSD) or as trauma-exposed controls (TECs). Main Outcomes and Measures: The main outcome was the slope parameter (b) of the logistic curve fitted to the valence rating. The slope parameter indicates the rate at which emotional response intensity changes with stimulus valence, reflecting how quickly the transition occurs between neutral and negatively valenced states. The secondary outcome was the association between emotional numbing (PCL-5 items 12-14) and the slope parameter. Results: A total of 1440 trauma-exposed individuals were included. The pPTSD group (n = 445) was younger (mean [SD] age, 36.1 [10.9] years) compared with the TEC group (mean [SD] age, 41.5 [13.3] years; P < .001). Sex distribution (427 women in the TEC group vs 230 in the pPTSD group) did not significantly differ between groups (P = .67). The pPTSD group exhibited a steeper slope (mean slope difference, -0.255; 89% highest posterior density [HPD], -0.340 to -0.171) compared with the controls. Across all individuals (n = 1440), a robust association was found between the slope and emotional numbing severity (mean [SD] additive value, 0.100 [0.031]; 89% HPD, 0.051-0.15). Additional analysis controlling for age confirmed the association between emotional numbing and transition sharpness (mean [SD] additive value, 0.108 [0.032]; 89% HPD, 0.056-0.159), without evidence of an age-related association (mean [SD] additive value, 0.031 [0.033]; 89% HPD, -0.022 to 0.083). Conclusions and Relevance: These findings support that individuals with PTSD undergo rapid transitions between neutral and negative emotional states, a phenomenon intensified by the severity of emotional numbing symptoms. Therapeutic interventions aimed at moderating these swift emotional transitions could potentially alleviate PTSD symptoms.

Some closure on exposure-Realigning the perspective on trauma treatment and finding a pathway forward: Reply to Brown (2024) and Najavits (2024).

We respond to commentaries by Brown (2024) and Najavits (2024) on our original work titled "To Expose or Not to Expose: A Comprehensive Perspective on Treatment for Posttraumatic Stress Disorder" (Rubenstein et al., 2024). Their work serves to augment the original argument that exposure is an important change factor in the amelioration of traumatic stress but should be viewed more broadly than traditional treatment paradigms suggest. We are grateful for this opportunity and aim to promote additional dialogue in the field about ways to improve upon existing models of trauma and its treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

To expose or not to expose: A comprehensive perspective on treatment for posttraumatic stress disorder.

Trauma-focused psychotherapies, in particular prolonged exposure (PE) therapy, have been recognized as the "gold standard" for the treatment of posttraumatic stress disorder (PTSD). But effectiveness and implementation data show that a large proportion of patients who undergo exposure therapy retain their PTSD diagnosis, and implementation studies have shown low engagement and high dropout rates. Meanwhile, non-trauma-focused therapies have shown promise in treating PTSD. In this review, we aim to answer the question of whether exposure is necessary to treat PTSD by integrating clinical and research literature from multiple perspectives. We review the roots of exposure therapy in both psychodynamic and behavioral paradigms and their proposed mechanisms. We then review non-trauma-focused treatments and their proposed mechanisms. We conclude that the specific form of exposure required by PE is not necessary for symptom remission. Finally, common psychotherapy factors may facilitate patient self-directed exposure outside of the therapy context. These findings should alter the direction of clinical research to identify the therapy processes that most effectively promote the processing of trauma memories. With respect to clinical practice, shared decision-making should allow for increased patient autonomy in choosing either trauma-focused or non-trauma-focused treatments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Structural Neuroimaging of Hippocampus and Amygdala Subregions in Posttraumatic Stress Disorder: A Scoping Review.

Numerous studies have explored the relationship between posttraumatic stress disorder (PTSD) and the hippocampus and the amygdala because both regions are implicated in the disorder's pathogenesis and pathophysiology. Nevertheless, those key limbic regions consist of functionally and cytoarchitecturally distinct substructures that may play different roles in the etiology of PTSD. Spurred by the availability of automatic segmentation software, structural neuroimaging studies of human hippocampal and amygdala subregions have proliferated in recent years. Here, we present a preregistered scoping review of the existing structural neuroimaging studies of the hippocampus and amygdala subregions in adults diagnosed with PTSD. A total of 3513 studies assessing subregion volumes were identified, 1689 of which were screened, and 21 studies were eligible for this review (total N = 2876 individuals). Most studies examined hippocampal subregions and reported decreased CA1, CA3, dentate gyrus, and subiculum volumes in PTSD. Fewer studies investigated amygdala subregions and reported altered lateral, basal, and central nuclei volumes in PTSD. This review further highlights the conceptual and methodological limitations of the current literature and identifies future directions to increase understanding of the distinct roles of hippocampal and amygdalar subregions in posttraumatic psychopathology.

Functional correlates of a novel 8-factor model of PTSD in U.S. military veterans: Results from the National Health and Resilience in Veterans Study.

Emerging evidence indicates that more nuanced models of posttraumatic stress disorder (PTSD) may better capture the condition's symptom structure. Recent theoretical and empirical work suggest that an 8-factor model of PTSD with separate internally- (e.g. flashbacks) and externally- (e.g. trauma-cue related physiological reactivity) generated intrusive symptom clusters may advance understanding of PTSD and its treatment and course. However, the model's functional and clinical significance still requires evaluation. To this end, we analyzed data from the National Health and Resilience in Veterans Study, a nationally representative sample of 3847 trauma-exposed U.S. military veterans. Multivariable regressions were performed to assess the relationship between the 8 PTSD symptom clusters, assessed using the PTSD Checklist for DSM-5, and clinical and functional measures. Results revealed that externally-generated intrusions were associated with higher odds of current depression and anxiety and worse mental, cognitive, and psychosocial functioning. Anhedonia (e.g., loss of interest in enjoyable activities) symptoms were associated with all the correlates tested, while negative affect (e.g., having strong negative feelings such as fear) symptoms were associated with all measures except depression. Avoidance symptoms were associated with lower odds of current anxiety while externalizing behavior symptoms were linked to higher odds of suicidal ideation. Anxious arousal symptoms were associated with lower odds of suicidal ideation but higher odds of PTSD-related impairment/distress, while dysphoric arousal symptoms were associated with higher odds of current depression, PTSD-related impairment/distress and worse mental and cognitive functioning. Results suggest that a more nuanced 8-factor model of PTSD symptoms may help inform understanding of the clinical and functional correlates of this multi-faceted disorder.

Effects of a dissociative drug on fronto-limbic resting-state functional connectivity in individuals with posttraumatic stress disorder: a randomized controlled pilot study.

RATIONALE: A subanesthetic dose of ketamine, a non-competitive N-methyl-D-aspartate glutamate receptor (NMDAR) antagonist, elicits dissociation in individuals with posttraumatic stress disorder (PTSD), who also often suffer from chronic dissociative symptoms in daily life. These debilitating symptoms have not only been linked to worse PTSD trajectories, but also to increased resting-state functional connectivity (RSFC) between medial prefrontal cortex (mPFC) and amygdala, supporting the conceptualization of dissociation as emotion overmodulation. Yet, as studies were observational, causal evidence is lacking. OBJECTIVES: The present randomized controlled pilot study examines the effect of ketamine, a dissociative drug, on RSFC between mPFC subregions and amygdala in individuals with PTSD. METHODS: Twenty-six individuals with PTSD received either ketamine (0.5mg/kg; n = 12) or the control drug midazolam (0.045mg/kg; n = 14) during functional magnetic resonance imaging (fMRI). RSFC between amygdala and mPFC subregions, i.e., ventromedial PFC (vmPFC), dorsomedial PFC (dmPFC) and anterior-medial PFC (amPFC), was assessed at baseline and during intravenous drug infusion. RESULTS: Contrary to pre-registered predictions, ketamine did not promote a greater increase in RSFC between amygdala and mPFC subregions from baseline to infusion compared to midazolam. Instead, ketamine elicited a stronger transient decrease in vmPFC-amygdala RSFC compared to midazolam. CONCLUSIONS: A dissociative drug did not increase fronto-limbic RSFC in individuals with PTSD. These preliminary experimental findings contrast with prior correlative findings and call for further exploration and, potentially, a more differentiated view on the neurobiological underpinning of dissociative phenomena in PTSD.

Evaluating a novel 8-factor dimensional model of PTSD in U.S. military veterans: Results from the National Health and Resilience in Veterans Study.

BACKGROUND: Accumulating data suggest that the structure of posttraumatic stress disorder (PTSD) symptoms may be more nuanced than proposed by prevailing nosological models. Emerging theory further suggests that an 8-factor model with separate internally- (e.g., flashbacks) and externally- (e.g., trauma cue-related emotional reactivity) generated intrusive symptoms may best represent PTSD symptoms. To date, however, scarce research has evaluated the fit of this model and whether index traumas are differentially associated with it in populations at high risk for trauma exposure, such as military veterans. METHODS: Data were analyzed from a nationally representative sample of 3847 trauma-exposed U.S. veterans who participated in the National Health and Resilience in Veterans Study. Confirmatory factor analyses were conducted to evaluate the fit of a novel 8-factor model of PTSD symptoms relative to 4-factor DSM-5 and empirically-supported 7-factor hybrid models. RESULTS: The 8-factor model fit the data significantly better than the 7-factor hybrid and 4-factor DSM-5 models. Combat exposure and harming others were more strongly associated with internally-generated intrusions, while interpersonal violence and disaster/accident showed stronger significant associations with externally-generated intrusions. LIMITATIONS: The 8-factor model requires validation in non-veteran and more diverse trauma-exposed populations, as well as with clinician-administered interviews. CONCLUSIONS: Results of this study provide support for a novel 8-factor model of PTSD symptoms that is characterized by separate internally- and externally-generated intrusions. They also suggest that certain index traumas may lead to differential expression of these symptoms.

Neural patterns differentiate traumatic from sad autobiographical memories in PTSD.

For people with post-traumatic stress disorder (PTSD), recall of traumatic memories often displays as intrusions that differ profoundly from processing of 'regular' negative memories. These mnemonic features fueled theories speculating a unique cognitive state linked with traumatic memories. Yet, to date, little empirical evidence supports this view. Here we examined neural activity of patients with PTSD who were listening to narratives depicting their own memories. An intersubject representational similarity analysis of cross-subject semantic content and neural patterns revealed a differentiation in hippocampal representation by narrative type: semantically similar, sad autobiographical memories elicited similar neural representations across participants. By contrast, within the same individuals, semantically similar trauma memories were not represented similarly. Furthermore, we were able to decode memory type from hippocampal multivoxel patterns. Finally, individual symptom severity modulated semantic representation of the traumatic narratives in the posterior cingulate cortex. Taken together, these findings suggest that traumatic memories are an alternative cognitive entity that deviates from memory per se.

Underlying Hippocampal Mechanism of Posttraumatic Stress Disorder Treatment Outcome: Evidence From Two Clinical Trials.

Background: The hippocampus plays an important role in the pathophysiology of posttraumatic stress disorder (PTSD) and its prognosis. Accumulating findings suggest that individuals with larger pretreatment hippocampal volume are more likely to benefit from PTSD treatment, but the mechanism underlying this effect is unknown. We investigated whether further increase in hippocampal volume during treatment explains the better prognosis of individuals with greater pretreatment hippocampal volume. Methods: We collected structural magnetic resonance imagesfrom patients with PTSD before and after treatment. We examined whether larger hippocampal volume moderates the effect of increased hippocampal volume during treatment on symptom reduction. Given the relatively small sample sizes of treatment studies with pre- and posttreatment magnetic resonance imaging, we focused on effect sizes and sought to replicate findings in an external sample. We tested our hypothesis in study 1 (N = 38; prolonged exposure therapy) and then tested whether the results could be externally replicated in study 2 (N = 20; ketamine infusion followed by exposure therapy). Results: Findings from study 1 revealed that increased right hippocampal volume during treatment was associated with greater PTSD symptom reduction only in patients with greater pretreatment right hippocampal volume (p = .03; η2 = 0.13, a large effect). Findings were partially replicated in study 2 for depressive symptoms (p = .034; η2 = 0.25, a very large effect) and for PTSD symptoms (p = .15; η2 = 0.15, a large effect). Conclusions: Elucidating increased hippocampal volume as one of the neural mechanisms predictive of therapeutic outcome for individuals with larger pretreatment hippocampal volume may help identify clinical targets for this subgroup.

Changes in mental health among U.S. military veterans during the COVID-19 pandemic: A network analysis.

Increases of symptoms of posttraumatic stress disorder (PTSD), anxiety and depression have been observed among individuals exposed to potentially traumatic events in the first months of the COVID-19 pandemic. Similarly, associations among different aspects of mental health, such as symptoms of PTSD and suicidal ideation, have also been documented. However, studies including an assessment prior to the onset and during the height of the pandemic are lacking. We investigated changes in symptoms of PTSD, depression, anxiety, suicidal ideation, and posttraumatic growth in a population-based sample of 1232 U.S. military veterans who experienced a potentially traumatic event during the first year of the pandemic. Symptoms were assessed prior to (fall/winter 2019) and one year into the pandemic (fall/winter 2020). We compared changes in symptom interrelations using network analysis, and assessed their associations with pandemic-related PTSD and posttraumatic growth symptoms. A subtle increase in psychopathological symptoms and a decrease in posttraumatic growth was observed one year into the pandemic. The peripandemic network was more densely connected, and pandemic-related PTSD symptoms were positively associated with age, anxiety, worst-event PTSD symptoms, and pandemic-related posttraumatic growth. Our findings highlight the resilience of veterans exposed to a potentially traumatic event during the first year of a pandemic. Similarly, the networks did not fundamentally change from prepandemic to one year into the pandemic. Despite this relative stability on a group level, individual reactions to potentially traumatic events could have varied substantially. Clinicians should individualize their assessments but be aware of the general resilience of most veterans.

Not all traumas are created equal: Phenotypic heterogeneity of PTSD symptoms in relation to index traumas in U.S. military veterans.

Posttraumatic stress disorder (PTSD) is prevalent in military veterans. Although exposure to trauma is subsumed under the diagnostic criteria for PTSD, there is great variability in index traumatic events, and the clinical presentation of PTSD may vary in individuals depending on the type of event experienced. We examined the relationship between different index traumas and PTSD symptoms in 3507 trauma-exposed U.S. military veterans who participated in the National Health and Resilience in Veterans Study. Results showed that interpersonal violence and combat/captivity was associated with greater overall severity of PTSD symptoms relative to illness/injury and disaster/accident. Interpersonal violence and combat/captivity were also associated with greater severity of intrusive, avoidance, negative affect, anhedonia, externalizing behaviors, and anxious and dysphoric arousal symptoms, relative to the other two categories. Implications of these findings for tailoring treatment approaches for PTSD in veterans are discussed.

Correlates of avoidance coping in trauma-exposed U.S. military veterans: Results from the National Health and Resilience in Veterans Study.

Avoidant coping strategies, which involve cognitions and behaviors aimed to avoid dealing with stressful experiences, are associated with adverse long-term mental and physical health outcomes. In response to traumatic events, these strategies can be maladaptive as they may interfere with the adaptive integration of traumatic events into consolidated memories. Using data from a nationally representative sample of more than 3000 trauma-exposed U.S. military veterans (mean time since trauma 30.9 years, SD = 19.9), we employed a network analytic approach to examine pairwise associations between key sociodemographic, personality, and psychosocial risk factors in relation to the endorsement of avoidant coping strategies. Results revealed that negative affect symptoms of posttraumatic stress disorder (PTSD) and adverse childhood experiences were positively associated with engagement in avoidance coping, and that greater emotional stability and conscientiousness were negatively associated with this measure. Secondary network analysis of individual negative affect symptoms of PTSD suggested that blaming oneself and/or others for the traumatic event, emotional neglect, and sexual abuse were most strongly linked to avoidance coping. Collectively, these results suggest that strong feelings of blame related to trauma, emotional neglect, and sexual abuse are associated with greater likelihood of engaging in avoidance coping, while emotional stability and conscientiousness are associated with a lower likelihood of engaging in such strategies.

Long term structural and functional neural changes following a single infusion of Ketamine in PTSD.

NMDA receptor antagonists have a vital role in extinction, learning, and reconsolidation processes. During the reconsolidation window, memories are activated into a labile state and can be reconsolidated in an altered form. This concept might have significant clinical implications in treating PTSD. In this pilot study we tested the potential of a single infusion of ketamine, followed by brief exposure therapy, to enhance post-retrieval extinction of PTSD trauma memories. 27 individuals diagnosed with PTSD were randomly assigned to receive either ketamine (0.5 mg/kg 40 min; N = 14) or midazolam (0.045 mg/kg; N = 13) after retrieval of the traumatic memory. 24 h following infusion, participants received a four-day trauma-focused psychotherapy. Symptoms and brain activity were assessed before treatment, at the end of treatment, and at 30-day follow-up. Amygdala activation to trauma scripts (a major biomarker of fear response) served as the main study outcome. Although PTSD symptoms improved equally in both groups, post-treatment, ketamine recipients showed a lower amygdala (-0.33, sd = 0.13, 95%HDI [-0.56,-0.04]) and hippocampus (-0.3 (sd = 0.19), 95%HDI [-0.65, 0.04]; marginal effect) reactivation to trauma memories, compared to midazolam recipients. Post-retrieval ketamine administration was also associated with decreased connectivity between the amygdala and hippocampus (-0.28, sd = 0.11, 95%HDI [-0.46, -0.11]), with no change in amygdala-vmPFC connectivity. Moreover, reduction in fractional anisotropy in bi-lateral uncinate fasciculus was seen in the Ketamine recipients compared with the midazolam recipients (right: post-treatment: -0.01108, 95% HDI [-0.0184,-0.003]; follow-up: -0.0183, 95% HDI [-0.02719,-0.0107]; left: post-treatment: -0.019, 95% HDI [-0.028,-0.011]; follow-up: -0.017, 95% HDI [-0.026,-0.007]). Taken together it is possible that ketamine may enhance post-retrieval extinction of the original trauma memories in humans. These preliminary findings show promising direction toward the capacity to rewrite human traumatic memories and modulate the fear response for at least 30 days post-extinction. When combined with psychotherapy for PTSD, further investigation of ketamine dose, timing of administration, and frequency of administration, is warranted.

Amygdala downregulation training using fMRI neurofeedback in post-traumatic stress disorder: a randomized, double-blind trial.

Hyperactivation of amygdala is a neural marker for post-traumatic stress disorder (PTSD) and improvement in control over amygdala activity has been associated with treatment success in PTSD. In this randomized, double-blind clinical trial we evaluated the efficacy of a real-time fMRI neurofeedback intervention designed to train control over amygdala activity following trauma recall. Twenty-five patients with PTSD completed three sessions of neurofeedback training in which they attempted to downregulate the feedback signal after exposure to personalized trauma scripts. For subjects in the active experimental group (N = 14), the feedback signal was from a functionally localized region of their amygdala associated with trauma recall. For subjects in the control group (N = 11), yoked-sham feedback was provided. Changes in control over the amygdala and PTSD symptoms served as the primary and secondary outcome measurements, respectively. We found significantly greater improvements in control over amygdala activity in the active group than in the control group 30-days following the intervention. Both groups showed improvements in symptom scores, however the symptom reduction in the active group was not significantly greater than in the control group. Our finding of greater improvement in amygdala control suggests potential clinical application of neurofeedback in PTSD treatment. Thus, further development of amygdala neurofeedback training in PTSD treatment, including evaluation in larger samples, is warranted.

Biological rhythms in COVID-19 vaccine effectiveness in an observational cohort study of 1.5 million patients.

BACKGROUNDCircadian rhythms are evident in basic immune processes, but it is unclear if rhythms exist in clinical endpoints like vaccine protection. Here, we examined associations between COVID-19 vaccination timing and effectiveness.METHODSWe retrospectively analyzed a large Israeli cohort with timestamped COVID-19 vaccinations (n = 1,515,754 patients over 12 years old, 99.2% receiving BNT162b2). Endpoints included COVID-19 breakthrough infection and COVID-19-associated emergency department visits and hospitalizations. Our main comparison was among patients vaccinated during morning (800-1159 hours), afternoon (1200-1559 hours), or evening hours (1600-1959 hours). We employed Cox regression to adjust for differences in age, sex, and comorbidities.RESULTSBreakthrough infections differed based on vaccination time, with lowest the rates associated with late morning to early afternoon and highest rates associated with evening vaccination. Vaccination timing remained significant after adjustment for patient age, sex, and comorbidities. Results were consistent in patients who received the basic 2-dose series and who received booster doses. The relationship between COVID-19 immunization time and breakthrough infections was sinusoidal, consistent with a biological rhythm that modifies vaccine effectiveness by 8.6%-25%. The benefits of daytime vaccination were concentrated in younger (<20 years old) and older patients (>50 years old). COVID-19-related hospitalizations varied significantly with the timing of the second booster dose, an intervention reserved for older and immunosuppressed patients (HR = 0.64, morning vs. evening; 95% CI, 0.43-0.97; P = 0.038).CONCLUSIONWe report a significant association between the time of COVID-19 vaccination and its effectiveness. This has implications for mass vaccination programs.FUNDINGNIH.

Comparative effectiveness of evidence-based psychotherapies for PTSD delivered in VA residential PTSD treatment.

BACKGROUND: Cognitive Processing Therapy (CPT) and Prolonged Exposure (PE) are first-line treatments for posttraumatic stress disorder (PTSD). There have been few direct comparisons of CPT and PE intended to determine their comparative effectiveness, none of which have examined outcomes among military veterans receiving these treatments in a residential setting such as the Department of Veterans Affairs (VA) residential rehabilitation treatment programs (RRTPs). Such work is essential given that these veterans are among the most complex and severely symptomatic patients with PTSD treated in VA. In this study we compared changes in PTSD and depressive symptoms across admission, discharge, four months and 12 months following discharge among veterans who received CPT or PE within VA RRTPs. METHODS: Using linear mixed models conducted on program evaluation data derived from the electronic medical record and follow-up surveys, we compared self-reported PTSD and depressive symptom outcomes among 1130 veterans with PTSD who were treated with individual CPT (n = 832, 73.5%) or PE (n = 297, 26.5%) in VA PTSD RRTPs in fiscal years 2018-2020. RESULTS: PTSD and depressive symptom severity did not significantly differ at any time points. The CPT and PE groups both showed large-sized reductions in PTSD (CPT d = 1.41, PE d = 1.51) and depression (CPT d = 1.01, PE d = 1.09) from baseline to 12-month follow-up. CONCLUSIONS: Outcomes for PE and CPT do not differ among a highly complex population of veterans with severe PTSD and several comorbid conditions that can make it difficult to engage in treatment.

Clinical significance of novel 8-factor model of DSM-5 PTSD in national VA PTSD residential treatment data: Internally- v. externally-cued intrusions.

BACKGROUND: Intrusion symptoms are a core defining feature of posttraumatic stress disorder (PTSD). It was recently proposed that intrusions may be comprised of two distinct underlying processes: internally-cued intrusions (e.g., trauma-related memories), and externally-cued intrusions (e.g., reactivity to trauma-related cues in one's environment). This is the first study to examine the functional correlates of these two intrusion clusters. METHODS: Participants included 7460 veterans discharged from 40 Veterans Affairs PTSD residential programs across the United States in fiscal years 2018 through 2020. Latent network modeling and structural equation modeling were used to assess the fit of an 8-factor model of PTSD symptoms, which were assessed using the PTSD Checklist for DSM-5 (PCL-5) PTSD symptoms at admission, and its association with symptoms of depression and generalized anxiety, and emotional and physical functioning. RESULTS: The 8-factor model, with separate intrusion factors, showed superior model fit to the DSM-5 4-factor, 5-factor dysphoric arousal, 6-factor anhedonia, and 7-factor hybrid models of PTSD. Internally-cued intrusions were uniquely associated with dysphoric arousal, decreased avoidance, and worse physical health functioning; whereas, externally-cued intrusions were uniquely associated with greater avoidance, anxious arousal, negative affect, increased generalized anxiety symptoms, and worse emotional functioning. LIMITATIONS: Limitations include the cross-sectional design and use of self-report measures. CONCLUSIONS: Findings provide initial support for the clinical utility of a novel 8-factor model of PCL-5 PTSD symptoms, which distinguishes internally- and externally-cued intrusions. These separate intrusion symptom clusters may offer greater specificity and utility in informing the prognosis of and tailored interventions for PTSD.

Distinguishing emotional numbing symptoms of posttraumatic stress disorder from major depressive disorder.

Emotional numbing symptoms are a core aspect of posttraumatic stress disorder (PTSD). Since the initial characterization of PTSD in DSM-III, emotional numbing symptoms have been revised and grouped under different symptom clusters (avoidance in DSM-IV, negative alterations in cognitions, and mood in DSM-5). Previous studies have found emotional numbing symptoms to be associated with greater PTSD severity, functional impairment, and worse treatment outcomes. Although considered an important feature, some argue that emotional numbing symptoms may simply reflect the manifestation of major depressive disorder (MDD) symptoms rather than be an inherent part of the PTSD phenotype. Here, we evaluated this question using two different data sets (N1 = 142; CAPS-5, N2 = 163; CAPS-4) of trauma-exposed individuals. First, we evaluated the unique variance of emotional numbing explained by diagnosis as binary variables (i.e., having PTSD, MDD, or both) and the severity of symptoms. Second, we examined the relative importance of each PTSD symptom in relation to emotional numbing symptoms. Results revealed that PTSD had a distinct contribution to the variance explaining emotional numbing symptoms above and beyond MDD. These findings suggest that emotional numbing should not be conceptualized as a simple manifestation of MDD symptoms. Rather, this symptom cluster may be a unique feature of PTSD that should be addressed within the context of trauma.

Longitudinal volumetric evaluation of hippocampus and amygdala subregions in recent trauma survivors.

The hippocampus and the amygdala play a central role in post-traumatic stress disorder (PTSD) pathogenesis. While alternations in volumes of both regions have been consistently observed in individuals with PTSD, it remains unknown whether these reflect pre-trauma vulnerability traits or acquired post-trauma consequences of the disorder. Here, we conducted a longitudinal panel study of adult civilian trauma survivors admitted to a general hospital emergency department (ED). One hundred eligible participants (mean age = 32.97 ± 10.97, n = 56 females) completed both clinical interviews and structural MRI scans at 1-, 6-, and 14-months after ED admission (alias T1, T2, and T3). While all participants met PTSD diagnosis at T1, only n = 29 still met PTSD diagnosis at T3 (a "non-Remission" Group), while n = 71 did not (a "Remission" Group). Bayesian multilevel modeling analysis showed robust evidence for smaller right hippocampus volume (P+ of ~0.014) and moderate evidence for larger left amygdala volume (P+ of ~0.870) at T1 in the "non-Remission" group, compared to the "Remission" group. Subregion analysis further demonstrated robust evidence for smaller volume in the subiculum and right CA1 hippocampal subregions (P+ of ~0.021-0.046) in the "non-Remission" group. No time-dependent volumetric changes (T1 to T2 to T3) were observed across all participants or between groups. Results support the "vulnerability trait" hypothesis, suggesting that lower initial volumes of specific hippocampus subregions are associated with non-remitting PTSD. The stable volume of all hippocampal and amygdala subregions does not support the idea of consequential, progressive, stress-related atrophy during the first critical year following trauma exposure.