Clinician-Administered Posttraumatic Stress Disorder Scale Research Articles

Altered gene expression and PTSD symptom dimensions in World Trade Center responders.

Despite experiencing a significant trauma, only a subset of World Trade Center (WTC) rescue and recovery workers developed posttraumatic stress disorder (PTSD). Identification of biomarkers is critical to the development of targeted interventions for treating disaster responders and potentially preventing the development of PTSD in this population. Analysis of gene expression from these individuals can help in identifying biomarkers of PTSD. We established a well-phenotyped sample of 371 WTC responders, recruited from a longitudinal WTC responder cohort using stratified random sampling, by obtaining blood, self-reported and clinical interview data. Using bulk RNA-sequencing from whole blood, we examined the association between gene expression and WTC-related PTSD symptom severity on (i) highest lifetime Clinician-Administered PTSD Scale (CAPS) score, (ii) past-month CAPS score, and (iii) PTSD symptom dimensions using a 5-factor model of re-experiencing, avoidance, emotional numbing, dysphoric arousal and anxious arousal symptoms. We corrected for sex, age, genotype-derived principal components and surrogate variables. Finally, we performed a meta-analysis with existing PTSD studies (total N = 1016), using case/control status as the predictor and correcting for these variables. We identified 66 genes significantly associated with total highest lifetime CAPS score (FDR-corrected p < 0.05), and 31 genes associated with total past-month CAPS score. Our more granular analyses of PTSD symptom dimensions identified additional genes that did not reach statistical significance in our analyses with total CAPS scores. In particular, we identified 82 genes significantly associated with lifetime anxious arousal symptoms. Several genes significantly associated with multiple PTSD symptom dimensions and total lifetime CAPS score (SERPINA1, RPS6KA1, and STAT3) have been previously associated with PTSD. Geneset enrichment of these findings has identified pathways significant in metabolism, immune signaling, other psychiatric disorders, neurological signaling, and cellular structure. Our meta-analysis revealed 10 genes that reached genome-wide significance, all of which were downregulated in cases compared to controls (CIRBP, TMSB10, FCGRT, CLIC1, RPS6KB2, HNRNPUL1, ALDOA, NACA, ZNF429 and COPE). Additionally, cellular deconvolution highlighted an enrichment in CD4 T cells and eosinophils in responders with PTSD compared to controls. The distinction in significant genes between total lifetime CAPS score and the anxious arousal symptom dimension of PTSD highlights a potential biological difference in the mechanism underlying the heterogeneity of the PTSD phenotype. Future studies should be clear about methods used to analyze PTSD status, as phenotypes based on PTSD symptom dimensions may yield different gene sets than combined CAPS score analysis. Potential biomarkers implicated from our meta-analysis may help improve therapeutic target development for PTSD.

Do early responders and treatment non-responders offer guidance to make CPT group a more effective treatment?

Treatment dropout has been problematic with evidence-based treatments for posttraumatic stress disorder (PTSD), including cognitive processing therapy (CPT). This study sought to evaluate whether CPT group contributed to symptom improvement among treatment completers and non-completers. Sixty-one Iraq and Afghanistan combat Veterans self-selected CPT group or treatment as usual (TAU) forming a convenience sample. Defining treatment completion as attending at least ninesessions: 18 completed treatment, 20 dropped-out (DOs); 20 completed TAU, 3 lost to TAU follow-up. Multiple Regression revealed significant pre-post-treatment improvement, the Clinician-Administered PTSDScale (CAPS-IV, F(5,40.1) = 2.53, p = 0.0436). Reviewing DOs' last available PTSD Checklist-Military Version scores before leaving treatment, six achieved clinically significant improvement of >10 points; seven a clinically reliable change of 5-10 points. These findings highlight that CPT group may be effective at reducing trauma-related symptoms among treatment completers and dropouts and point to the utility of a clinical definition of good treatment end-state.

Sex-differential PTSD symptom trajectories across one year following suspected serious injury

ABSTRACT Background Recent years have shown an increased application of prospective trajectory-oriented approaches to posttraumatic stress disorder (PTSD). Although women are generally considered at increased PTSD risk, sex and gender differences in PTSD symptom trajectories have not yet been extensively studied. Objective To perform an in-depth investigation of differences in PTSD symptom trajectories across one-year post-trauma between men and women, by interpreting the general trends of trajectories observed in sex-disaggregated samples, and comparing within-trajectory symptom course and prevalence rates. Method We included N = 554 participants (62.5% men, 37.5% women) from a multi-centre prospective cohort of emergency department patients with suspected severe injury. PTSD symptom severity was assessed at 1, 3, 6, and 12 months post-trauma, using the Clinician-Administered PTSD Scale for DSM-IV. Latent growth mixture modelling on longitudinal PTSD symptoms was performed within the sex-disaggregated and whole samples. Bayesian modelling with informative priors was applied for reliable model estimation, considering the imbalanced prevalence of the expected latent trajectories. Results In terms of general trends, the same trajectories were observed for men and women, i.e. resilient, recovery, chronic symptoms and delayed onset. Within-trajectory symptom courses were largely comparable, but resilient women had higher symptoms than resilient men. Sex differences in prevalence rates were observed for the recovery (higher in women) and delayed onset (higher in men) trajectories. Model fit for the sex-disaggregated samples was better than for the whole sample, indicating preferred application of sex-disaggregation. Analyses within the whole sample led to biased estimates of overall and sex-specific trajectory prevalence rates. Conclusions Sex-disaggregated trajectory analyses revealed limited sex differences in PTSD symptom trajectories within one-year post-trauma in terms of general trends, courses and prevalence rates. The observed biased trajectory prevalence rates in the whole sample emphasize the necessity to apply appropriate statistical techniques when conducting sex-sensitive research.

Cognitive Processing Therapy for Concurrent Posttraumatic Stress Disorder and Psychogenic Nonepileptic Seizures: A Case Study

Psychogenic nonepileptic seizures (PNES) are the number-one medically unexplained symptom encountered by neurologists (Brown & Reuber, 2016) and account for approximately 30% of patients referred to epilepsy centers (Leu et al., 2020). Episodes of PNES physically resemble epileptic seizures; however, electrical activity within the brain appears to be within normal limits. Currently, there are no medications available to specifically manage PNES (Hingray et al., 2017). Although studies focused on the impact of psychological interventions for PNES are limited, cognitive behavioral therapy (CBT) approaches appear to be effective (LaFrance et al., 2014). Prior exposure to a traumatic event is common for patients with PNES (Brown & Reuber, 2016; Myers et al., 2017). Cognitive Processing Therapy (CPT) is an evidence-based psychotherapy for posttraumatic stress disorder (PTSD). CPT is effective for a variety of traumatic experiences, and asks patients to address avoidance (e.g., of situations, emotions) and challenge maladaptive thought patterns (Resick et al., 2017). In this case study, a 29-year-old Caucasian female patient presented for treatment with comorbid PTSD and PNES. Current PTSD diagnosis was indicated by self-reported and clinician-administered assessment, which included the Clinician Administered PTSD Scale for DSM-5 (CAPS-5 = 52 out of 80) and the PTSD Checklist for DSM-5 (PCL-5 = 59 out of 80). This patient’s Criterion A trauma involved repeated domestic sexual assault as an adult, which occurred for several years. PNES was diagnosed approximately 1 year prior by a neuropsychologist. At the start of treatment, the patient endorsed PNES almost daily, which prevented her from maintaining a job or driving a vehicle. The patient was an early and successful responder to CPT, as she participated in 8 of 12 sessions. In addition to significantly lower self-reported PTSD and depressive symptom severity (PCL-5 = 5; PHQ-9 = 2), she did not experience PNES in the 17 days leading up to her final session. As the patient’s avoidance of distressing trauma-related thoughts and emotions decreased, so too did her PNES. This case study provides neurologists with a promising treatment approach for patients with PNES and PTSD.

Impact of Treatment Setting and Format on Symptom Severity Following Cognitive Processing Therapy for Posttraumatic Stress Disorder

Preliminary data suggest cognitive processing therapy (CPT) significantly reduces posttraumatic stress disorder (PTSD) symptom severity among military personnel and veterans when delivered over 12 days and combined with daily recreational activities (Bryan et al., 2018). The present study aimed to examine how therapy pace (i.e., daily vs. weekly sessions) and setting (i.e., clinic vs. recreational) impacts change in PTSD symptom severity. Forty-five military personnel and veterans diagnosed with PTSD chose to receive CPT (a) daily at a recreational facility with recreational programming, (b) daily on a university campus without recreational programming, and (c) weekly on a university campus without recreational programming. PTSD symptom severity was assessed with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) and the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5). Reductions in CAPS-5 and PCL-5 scores were large and statistically significant across all three settings (Cohen’s ds > 2.1). As compared to reductions in CAPS-5 and PCL-5 scores in daily therapy at a recreational facility (CAPS-5: d = 1.63–2.40; PCL-5: d = 1.99–2.17), reductions in CAPS-5 and PCL-5 scores were significantly larger in daily therapy on campus, CAPS-5: t(80) = –2.9, p = .005, d = 2.23–2.69; PCL-5: t(78) = 2.6, p = .010, d = 2.54–4.43, but not weekly therapy on campus, CAPS-5: t(80) = 0.2, p = .883, d = 1.04–2.47; PCL-5: t(78) = 1.0, p = .310, d = 1.77–3.44. Participants receiving daily therapy on campus and weekly therapy on campus also had higher rates of clinically significant improvement and good end-state functioning. Results support the effectiveness of CPT across multiple treatment settings and formats and suggest that daily CPT may be less effective when delivered in combination with recreational activities.

Heart Rate Variability Features as Predictors of Intermittent Theta-Burst Stimulation Response in Posttraumatic Stress Disorder

BackgroundPosttraumatic stress disorder (PTSD) is associated with autonomic dysfunction as indicated by deficits in the sympathetic and parasympathetic nervous systems. These abnormalities are expressed as elevated heart rate and reduced heart rate variability (HRV), respectively. Intermittent theta-burst stimulation (iTBS), a form of transcranial magnetic stimulation, has demonstrated effectiveness in PTSD. Nevertheless, it remains unclear whether HRV may be an iTBS biomarker for PTSD and whether iTBS impacts autonomic activity. Materials and MethodsFifty veterans with PTSD participated in a randomized controlled trial, receiving ten daily sessions of sham-controlled iTBS (right dorsolateral prefrontal cortex, 1800 pulses/day, 80% active motor threshold, 9.5 min). With a usable dataset (N = 47), HRV parameters were assessed as predictors of clinical response immediately after stimulation. iTBS effects on autonomic response (mean RR interval, root mean square of successive differences [RMSSD], total power [TP], and low-frequency/high-frequency [LF/HF] ratio) were evaluated using an ultra-short approach. ResultsTP and RMSSD were significant predictors of acute clinical response to iTBS. Individuals with higher TP had better response to iTBS with improved symptoms on the Clinician-Administered PTSD Scale (rs = −0.58, p = 0.004), and higher functionality on the Social and Occupational Function Scale (rs = 0.43, p = 0.04). Similarly, higher RMSSD was associated with superior outcomes (rs = −0.44, p = 0.04). No other significant changes in HRV metrics were observed (p ≥ 0.05). ConclusionsOur findings indicate that autonomic activity is a potential low-cost and technically simple predictive biomarker of iTBS response in PTSD. Less autonomic dysfunction was associated with superior clinical improvements with iTBS. Future studies might consider HRV acquisition during iTBS, as well as prospective testing of these findings in patients with elevated hyperarousal.

Reliable and clinically significant change in the clinician-administered PTSD Scale for DSM-5 and PTSD Checklist for DSM-5 among male veterans.

We calculated the reliable change index (RCI) and clinically significant change (CSC) values for two widely used measures of posttraumatic stress disorder (PTSD): The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the PTSD Checklist for DSM-5 (PCL-5) and examined how symptom changes at these thresholds related to improvements in psychosocial functioning. We used data from three independent samples of male military veterans, including two randomized controlled trials for PTSD (N = 198 for Sample 1 and N = 102 for Sample 2) and a cross-sectional study of primary care patients (N = 228). For Sample 1, within-person change in CAPS-5 and PCL-5 scores of ≥ 13 and 15, respectively, was indicative of reliable change. For Sample 2, within-person change in CAPS-5 and PCL-5 scores of ≥ 12 and 18, respectively, was indicative of reliable change. Scores of ≤ 8 and 28 on the CAPS-5 and PCL-5, respectively, indicated a participant is more likely to belong to the non-PTSD population than the PTSD population (i.e., clinically significant change) in both Samples 1 and 2. Participants who exhibited reliable or CSC reported significantly better psychosocial functioning at all posttreatment assessments than those who did not. Results provide thresholds for identifying clinically meaningful PTSD symptom change using these measures. Care should be taken to interpret these values appropriately and relative to numerous other definitions for meaningful symptom change. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Augmenting PTSD treatment with physical activity: study protocol of the APPART study (Augmentation for PTSD with Physical Activity in a Randomized Trial)

ABSTRACT Background New intensive trauma-focused treatment (TFT) programmes that incorporate physical activity have been developed for people with post-traumatic stress disorder (PTSD). However, the unique contribution of physical activity within these intensive TFT programmes has never been investigated in a controlled manner. Objectives This randomized controlled trial will investigate the effectiveness of physical activity added to an intensive TFT programme. In addition, the study aims to investigate the underlying mechanisms of the effects of physical activity on the change in PTSD symptoms. Methods Individuals with PTSD (N = 120) will be randomly allocated to two conditions: a physical activity or a non-physical active control condition. All participants will receive the same intensive TFT lasting eight days within two consecutive weeks, in which daily prolonged exposure and EMDR therapy sessions, and psycho-education are combined. The amount of physical activity will differ per condition. While the physical activity condition induces daily physical activities with moderate intensity, in the non-physical active control condition no physical activity is prescribed; but instead, a controlled mixture of guided (creative) tasks is performed. The two primary outcome measures are change in PTSD symptoms from pre- to post-treatment and at six months follow-up, measured with the Clinician-Administered PTSD Scale (CAPS-5), and the PTSD Checklist for DSM-5 (PCL-5). Additionally, self-reported sleep problems, depressive symptoms, emotion regulation, dissociation symptoms and anxiety sensitivity will be measured as potential underlying mechanisms. Conclusions This study will contribute to the research field of augmentation strategies for PTSD treatment by investigating the effectiveness of physical activity added to intensive TFT. Trial registration This trial is registered in the Netherlands Trial Register (Trial NL9120).

Impact of mothers’ IPV-PTSD on their capacity to predict their child’s emotional comprehension and its relationship to their child’s psychopathology

ABSTRACT Background Previous studies demonstrated that when the violence-exposed child becomes a mother and interacts with her own child during early sensitive periods for social-emotional development, she may have difficulties providing sensitive responsiveness to the child’s emotional communication. Such difficulties place the child’s development of emotional comprehension (EC) and related self-regulation at risk. The aim of this study was to examine how mothers’ interpersonal violence-related posttraumatic disorder (IPV-PTSD) would affect their children’s EC and their own ability to predict their children’s EC. We also investigated how mothers’ predictive ability would correlate with child psychopathology. Methods Sixty-one mother–child dyads (36 with IPV-PTSD) participated in this study. Children’s (mean age = 7.0 years, SD = 1.1) EC was assessed with the Test of Emotion Comprehension (child TEC) and their psychopathology as reported by the mother was assessed with the Child Behaviour Checklist (CBCL) and as evaluated by a clinician using selected modules of the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Mothers were measured for IPV-PTSD with the Clinician Administered PTSD Scale (CAPS) and for their capacity to predict their child’s emotional comprehension (mother-responding-as-child TEC; mTEC). Results We found no significant between-group differences in children’s level of EC. Maternal PTSD was associated with lower scores on the mTEC, however. Reduced maternal scores on the mTEC were significantly associated with maternal report of increased aggressive child behaviour and with depression symptoms on the K-SADS. Further, scores on the mTEC interacted with maternal report of child aggression on child oppositional defiant disorder (ODD) symptoms on the K-SADS. Conclusion These findings support that improving maternal emotional comprehension may help reduce child risk for psychiatric morbidity in this population.

The nature of posttraumatic stress disorder in treatment-seeking first responders

ABSTRACT Background Approximately 10% of first responders report posttraumatic stress disorder (PTSD). Although reports within first responders suggest that they have distinct symptom presentations, there is a need to understand how the clinical profiles of first responders may differ from others seeking treatment for PTSD. Objective This study compared the PTSD symptom profiles of first responder and civilians seeking treatment for PTSD. Method Participants self-referred to the Traumatic Stress Clinic (University of New South Wales, Sydney) for enrolment in out-patient treatment trials for PTSD. Participants comprised people of mean age 41.72 years (SD = 10.71) who met DSM-IV criteria for PTSD. The sample was composed of 128 first responders and 182 civilians. Clinician-administered interviews of PTSD (Clinician-Administered PTSD Scale) and depression were conducted, as well as measures of self-report measures of depression, alcohol use, posttraumatic appraisals, and anger. Results First responders reported greater rates of dysphoric cluster of symptoms, including diminished interest, emotional numbing, and social detachment, and less psychological reactivity and avoidance of situations, than civilians with PTSD. Beyond PTSD symptoms, first responders also reported more severe levels of depression and suppressed anger. Conclusions These findings indicate that treatment-seeking first responders present with a distinct clinical profile that is characterized by dysphoric symptoms. These symptoms can predict poor treatment response and require specific attention in treating PTSD in first responders.

Assessment of early neurocognitive functioning increases the accuracy of predicting chronic PTSD risk.

Post-traumatic stress disorder (PTSD) is a protracted and debilitating consequence of traumatic events. Identifying early predictors of PTSD can inform the disorder's risk stratification and prevention. We used advanced computational models to evaluate the contribution of early neurocognitive performance measures to the accuracy of predicting chronic PTSD from demographics and early clinical features. We consecutively enrolled adult trauma survivors seen in a general hospital emergency department (ED) to a 14-month long prospective panel study. Extreme Gradient Boosting algorithm evaluated the incremental contribution to 14 months PTSD risk of demographic variables, 1-month clinical variables, and concurrent neurocognitive performance. The main outcome variable was PTSD diagnosis, 14 months after ED admission, obtained by trained clinicians using the Clinician-Administered PTSD Scale (CAPS). N = 138 trauma survivors (mean age = 34.25 ± 11.73, range = 18-64; n = 73 [53%] women) were evaluated 1 month after ED admission and followed for 14 months, at which time n = 33 (24%) met PTSD diagnosis. Demographics and clinical variables yielded a discriminatory accuracy of AUC = 0.68 in classifying PTSD diagnostic status. Adding neurocognitive functioning improved the discriminatory accuracy (AUC = 0.88); the largest contribution emanating from poorer cognitive flexibility, processing speed, motor coordination, controlled and sustained attention, emotional bias, and higher response inhibition, and recall memory. Impaired cognitive functioning 1-month after trauma exposure is a significant and independent risk factor for PTSD. Evaluating cognitive performance could improve early screening and prevention.

Life threat during assaultive trauma: Critical posttraumatic stress disorder risk factors for injured patients.

Rates of posttraumatic stress disorder (PTSD) among injury survivors are higher relative to the general population, supporting the need to identify those most at risk for PTSD following injury given negative impact of PTSD on recovery. Perceived life threat and assaultive trauma are consistent risk factors for subsequent PTSD development, although less work has explored them in combination. The current study evaluated whether trauma type (assaultive vs. nonassaultive) and perceived life threat, together, led to greater PTSD symptoms 1 month and 6 months postinjury. Participants included adult injured trauma survivors admitted to a level 1 trauma center. While hospitalized, perceived life threat during trauma was assessed and mechanism of injury was collected via record review and was collapsed into two categories: assaultive and nonassaultive. The Clinician-Administered PTSD Scale (Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition]) was administered at 1 month (N = 137) and 6 months (N = 220) after injury. The four symptoms clusters of PTSD (intrusions, avoidance, hyperarousal, and negative mood/cognitions) were examined using four 2 (time) × 2 (life threat) × 2 (trauma type) mixed methods analyses of variance to assess differences based on risk factors and time. Results showed significant interaction effects of life threat, trauma type, and time for intrusive symptoms and avoidance symptoms. Individuals with life threat during assaultive traumas maintained heightened intrusive symptoms across time and increased avoidance at 6 months. On the other hand, participants with either life threat or assaultive traumas had decreased symptoms at 6 months. Experiencing assaultive trauma and life threat led to greater symptoms of PTSD. Individuals with assaultive traumas who experienced life threat may represent a specific at-risk group following injury. Avoidance can protract functional impairment and impede access to care, negatively impacting recovery. This study highlights a need to assess for these peritrauma factors during hospitalization and supports early intervention targeting avoidance and intrusive symptoms in this group. Prognostic/Epidemiologic, Level IV.

Confirmatory factor analysis of the Clinician-Administered PTSD Scale (CAPS-5) based on DSM-5 vs. ICD-11 criteria

ABSTRACT Introduction Many studies have investigated the latent structure of the DSM-5 criteria for posttraumatic stress disorder (PTSD). However, most research on this topic was based on self-report data. We aimed to investigate the latent structure of PTSD based on a clinical interview, the Clinician-Administered PTSD Scale (CAPS-5). Method A clinical sample of 345 participants took part in this multi-centre study. Participants were assessed with the CAPS-5 and the Posttraumatic Stress Disorder Checklist (PCL-5). We evaluated eight competing models of DSM-5 PTSD symptoms and three competing models of ICD-11 PTSD symptoms. Results The internal consistency of the CAPS-5 was replicated. In CFAs, the Anhedonia model emerged as the best fitting model within all tested DSM-5 models. However, when compared with the Anhedonia model, the non-nested ICD-11 model as a less complex three-factor solution showed better model fit indices. Discussion We discuss the findings in the context of earlier empirical findings as well as theoretical models of PTSD.

Comparison of Prolonged Exposure vs Cognitive Processing Therapy for Treatment of Posttraumatic Stress Disorder Among US Veterans

IMPORTANCEPosttraumatic stress disorder (PTSD) is a prevalent and serious mental health problem. Although there are effective psychotherapies for PTSD, there is little information about their comparative effectiveness.OBJECTIVETo compare the effectiveness of prolonged exposure (PE) vs cognitive processing therapy (CPT) for treating PTSD in veterans.DESIGN, SETTING, AND PARTICIPANTSThis randomized clinical trial assessed the comparative effectiveness of PE vs CPT among veterans with military-related PTSD recruited from outpatient mental health clinics at 17 Department of Veterans Affairs medical centers across the US from October 31, 2014, to February 1, 2018, with follow-up through February 1, 2019. The primary outcome was assessed using centralized masking. Tested hypotheses were prespecified before trial initiation. Data were analyzed from October 5, 2020, to May 5, 2021.INTERVENTIONSParticipants were randomized to 1 of 2 individual cognitive-behavioral therapies, PE or CPT, delivered according to a flexible protocol of 10 to 14 sessions.MAIN OUTCOMES AND MEASURESThe primary outcome was change in PTSD symptom severity on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) from before treatment to the mean after treatment across posttreatment and 3- and 6-month follow-ups. Secondary outcomes included other symptoms, functioning, and quality of life.RESULTSAnalyses were based on all 916 randomized participants (730 [79.7%] men and 186 [20.3%] women; mean [range] age 45.2 [21–80] years), with 455 participants randomized to PE (mean CAPS-5 score at baseline, 39.9 [95% CI, 39.1–40.7] points) and 461 participants randomized to CPT (mean CAPS-5 score at baseline, 40.3 [95% CI, 39.5–41.1] points). PTSD severity on the CAPS-5 improved substantially in both PE (standardized mean difference [SMD], 0.99 [95% CI, 0.89–1.08]) and CPT (SMD, 0.71 [95% CI, 0.61–0.80]) groups from before to after treatment. Mean improvement was greater in PE than CPT (least square mean, 2.42 [95% CI, 0.53–4.31]; P = .01), but the difference was not clinically significant (SMD, 0.17). Results for self-reported PTSD symptoms were comparable with CAPS-5 findings. The PE group had higher odds of response (odds ratio [OR], 1.32 [95% CI, 1.00–1.65]; P < .001), loss of diagnosis (OR, 1.43 [95% CI, 1.12–1.74]; P < .001), and remission (OR, 1.62 [95% CI, 1.24–2.00]; P < .001) compared with the CPT group. Groups did not differ on other outcomes. Treatment dropout was higher in PE (254 participants [55.8%]) than in CPT (215 participants [46.6%]; P < .01). Three participants in the PE group and 1 participant in the CPT group were withdrawn from treatment, and 3 participants in each treatment dropped out owing to serious adverse events.CONCLUSIONS AND RELEVANCEThis randomized clinical trial found that although PE was statistically more effective than CPT, the difference was not clinically significant, and improvements in PTSD were meaningful in both treatment groups. These findings highlight the importance of shared decision-making to help patients understand the evidence and select their preferred treatment.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT01928732

Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial.

This study tested the efficacy of repeated intravenous ketamine doses to reduce symptoms of posttraumatic stress disorder (PTSD). Veterans and service members with PTSD (n = 158) who failed previous antidepressant treatment were randomized to 8 infusions administered twice weekly of intravenous placebo (n = 54), low dose (0.2 mg/kg; n = 53) or standard dose (0.5 mg/kg; n = 51) ketamine. Participants were assessed at baseline, during treatment, and for 4 weeks after their last infusion. Primary analyses used mixed effects models. The primary outcome measure was the self-report PTSD Checklist for DSM-5 (PCL-5), and secondary outcome measures were the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Montgomery Åsberg Depression Rating Scale (MADRS). There were no significant group-by-time interactions for PTSD symptoms measured by the PCL-5 or CAPS-5. The standard ketamine dose ameliorated depression measured by the MADRS significantly more than placebo. Ketamine produced dose-related dissociative and psychotomimetic effects, which returned to baseline within 2 h and were less pronounced with repeated administration. There was no evidence of differential treatment discontinuation by ketamine dose, consistent with good tolerability. This clinical trial failed to find a significant dose-related effect of ketamine on PTSD symptoms. Secondary analyses suggested that the standard dose exerted rapid antidepressant effects. Further studies are needed to determine the role of ketamine in PTSD treatment. ClinicalTrials.gov identifier: NCT02655692.

Effect of Written Exposure Therapy vs Cognitive Processing Therapy on Increasing Treatment Efficiency Among Military Service Members With Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) occurs more commonly among military service members than among civilians; however, despite the availability of several evidence-based treatments, there is a need for more efficient evidence-based PTSD treatments to better address the needs of service members. Written exposure therapy is a brief PTSD intervention that consists of 5 sessions with no between-session assignments, has demonstrated efficacy, and is associated with low treatment dropout rates, but prior randomized clinical trials of this intervention have focused on civilian populations. To investigate whether the brief intervention, written exposure therapy, is noninferior in the treatment of PTSD vs the more time-intensive cognitive processing therapy among service members diagnosed with PTSD. The study used a randomized, noninferiority design with a 1:1 randomization allocation. Recruitment for the study took place from August 2016 through October 2020. Participants were active-duty military service members diagnosed with posttraumatic stress disorder. The study was conducted in an outpatient setting for service members seeking PTSD treatment at military bases in San Antonio or Killeen, Texas. Participants received either written exposure therapy, which consisted of 5 weekly sessions, or cognitive processing therapy, which consisted of 12 twice-weekly sessions. Participants were assessed at baseline and at 10, 20, and 30 weeks after the first treatment session. The primary outcome measure was PTSD symptom severity assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Noninferiority was defined as the difference between the 2 groups being less than the upper bound of the 1-sided 95% CI-specified margin of 10 points on the CAPS-5. Overall, 169 participants were included in the study. Participants were predominantly male (136 [80.5%]), serving in the Army (167 [98.8%]), with a mean (SD) age of 34 (8) years. Eighty-five participants were randomly assigned to written exposure therapy, with 65 (76.5%) completing all treatment sessions, and 84 to cognitive processing therapy, with 47 (54.8%) completing all treatment sessions. Findings indicated that written exposure therapy was noninferior to cognitive processing therapy, with the largest difference in change in outcome between the treatment conditions of 3.96 points on the outcome measure. The 1-sided 95% CI upper limit was less than 10 points across time points in both groups and ranged from 4.59 at week 30 to 6.81 at week 10. Within-condition effect sizes ranged from a Cohen d of 0.48 for the written exposure therapy group in the intention-to-treat analysis at week 10 to 0.95 for the cognitive processing therapy group in the per-protocol analysis at week 10, and between-condition effect size ranged from 0.06 in the intention-to-treat analysis at week 30 to 0.22 in the per-protocol analysis at week 10. In this randomized clinical trial, support was found for an effective and more efficient PTSD treatment approach for service members. Future research should determine who does and does not benefit from PTSD treatment to best maximize treatment outcomes. ClinicalTrials.gov Identifier: NCT03033602.

Distress tolerance: prospective associations with cognitive-behavioral therapy outcomes in adults with posttraumatic stress and substance use disorders

ABSTRACT 74Distress tolerance (DT; perceived or actual ability to tolerate aversive physical or emotional states) is related to both posttraumatic stress disorder (PTSD) symptoms and substance use disorders (SUD). This investigation evaluates self-report and behavioral measures of DT as potential predictors of PTSD and SUD cognitive-behavioral therapy outcomes. Participants included 41 treatment-seeking adults (53.7% women; 73.2% African American; M age = 44.90, SD = 9.68) who met at least four symptoms of DSM-5 PTSD and DSM-IV substance dependence, assessed via structured interviews. At baseline (pre-treatment), participants completed the Distress Tolerance Scale (DTS), Mirror-Tracing Persistence Task (MTPT), Breath Holding task, and Paced Auditory Serial Addition Task. The Clinician-Administered PTSD Scale for DSM-5 severity scores and percent days of primary substance use, measured via Timeline Follow-back, were used as indicators of PTSD symptoms and substance use, respectively. Covariates included treatment condition, baseline PTSD symptom severity, and baseline substance use. Lower perceived DT at baseline (DTS total score) was associated with higher PTSD symptom severity at end-of-treatment. Lower behavioral DT at baseline (MTPT duration) was associated with higher substance use at the conclusion of treatment (i.e. proportion of number of use days to total number of days between two final treatment sessions).

Neural Correlates of Traumatic Brain Injury in Women Survivors of Intimate Partner Violence: A Structural and Functional Connectivity Neuroimaging Study.

More than one-third of women in the United States experience intimate partner violence (IPV) in their lifetime, increasing their risk for traumatic brain injury (TBI). Despite the prevalence of TBI among IPV survivors, research is sparse in comparison with parallel populations (eg, military, accidents, sports). This pilot study aimed to provide a preliminary investigation of the effect of TBI on brain morphometry and resting-state functional connectivity in women who experience IPV. A total of 45 community-dwelling women survivors of IPV who screened positive for posttraumatic stress disorder (PTSD). Participants completed comprehensive assessments of trauma exposure, PTSD, TBI history, and brain neurological health. Twenty-three participants (51.1%) met diagnostic criteria for lifetime TBI. Of these, 15 participants experienced 1 or more TBIs resulting from IPV. The remaining participants experienced TBI from non-IPV exposures (eg, sports/motor vehicle accident). Surface-based neuroimaging analyses were performed to examine group differences in cortical thickness and in functional connectivity of amygdala and isthmus cingulate seeds to examine emotion regulation and the default mode network, respectively. Boston Assessment of Traumatic Brain Injury-Lifetime for Intimate Partner Violence (BAT-L/IPV); Clinician Administered PTSD Scale (CAPS); structural and functional neuroimaging. History of lifetime TBI in women IPV survivors was associated with differences in cortical thickness as well as functional connectivity between the isthmus cingulate seed and a variety of regions, including superior parietal and frontal cortices. Individuals with IPV-related TBI showed lower cortical thickness in the right paracentral gyrus than individuals with TBI from other non-IPV etiologies. Significant differences in brain structure and connectivity were observed in individuals with IPV and TBI. A lower mean cortical thickness of the paracentral gyrus was associated with TBI due to IPV than TBI from other etiologies. Although preliminary, findings from this pilot study present a step toward identifying potential mechanisms by which IPV and TBI secondary to IPV impact brain health in women.

The Role of the Endocannabinoids 2-AG and Anandamide in Clinical Symptoms and Treatment Outcome in Veterans with PTSD

Background Although current treatments for Post-Traumatic Stress Disorder (PTSD) in war veterans are effective, unfortunately 30–50% still do not benefit from these treatments. Trauma-focused therapies, eg exposure therapy, are primarily based on extinction processes in which the endocannabinoid system (ECS) plays a significant role. Therefore, it can be hypothesized that poor treatment response on trauma-focused therapy due to extinction deficits may be associated with a poorly functioning ECS. The present study examined whether the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) are associated with post-treatment symptom reduction. Methods Blood plasma levels of AEA and 2-AG were determined in war veterans with a PTSD diagnosis (n = 54) and combat controls (n = 26) before and after a 6–8 month interval. During this period veterans with PTSD received trauma-focused therapy (eg cognitive behavioral therapy with exposure or eye-movement desensitization and reprocessing). Clinical symptoms were assessed before and after therapy with the Clinician Administered PTSD Scale (CAPS), State-Trait Anxiety Inventory (STAI) and Mood and Anxiety Symptom Questionnaire (MASQ). Results Regression analysis demonstrated that pretreatment endocannabinoid levels were not predictive of PTSD symptom reduction. Additionally, baseline endocannabinoid levels did not differ between either PTSD and combat controls or between combat controls, treatment responders, and non-responders. Only cortisol levels significantly decreased over time from pre- to posttreatment (p = .041). Endocannabinoid levels were significantly lower in individuals who reported cannabis use during their lifetime, independent of PTSD diagnosis. Furthermore, correlation analysis revealed that pretreatment 2-AG levels in PTSD were positively correlated with anxious arousal (r = .354, p = .015) and negatively with avoidance symptoms (r = -.271, p = .048). Both posttreatment AEA and 2-AG were positively correlated with trait anxiety (AEA r = .459, p = .003; 2-AG r = .423, p = .006), anxious arousal (AEA r = .351, p = .024; 2-AG r = .311, p = .048) and general distress depression symptoms (AEA r = .414, p = .007; 2-AG r = .374, p = .016). Conclusion Since endocannabinoids are mainly generated ‘on demand’, future work could benefit by investigating endocannabinoid circulation under both baseline and stressful conditions. In line with previous research cannabis use was associated with lower endocannabinoid levels. The correlation analysis between pre- and posttreatment endocannabinoid levels and pre- and posttreatment clinical symptomatology were exploratory analysis and should be replicated in future research.

Post-Traumatic Stress Disorder (PTSD) biomarker identification using a deep learning model

Post-traumatic stress disorder (PTSD) is a neuropsychological disorder in which individuals struggle to recover from a traumatizing event. It affects a significant population, including COVID-19 patients, frontline health workers, and war veterans. Given biases associated with self-assessment and diagnosis of PTSD, researchers are actively searching for unbiased biological markers (biomarkers) for predicting PTSD status. The Systems Biology of PTSD Consortium has collected candidate biomarkers for PTSD using molecular and clinical measurements of male war veterans between the ages of 20 and 60. PTSD-positive and negative subjects were separated based on the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Clinician Administered PTSD Scale (CAPS) scores, derived from structured interviews to measure an individual’s abundance of symptoms, such as re-experiencing, flashbacks, and hyperarousal. CAPS scores higher than 40 were considered PTSD-positive and below 20 were considered negative. We created artificial neural network models to classify PTSD-positive and negative individuals based on metabolomics, micro-RNA (miRNA), protein expression, endocrine markers, and DNA methylation datasets. Model training involved 64 iterations of a Bayesian Hyperparameter Optimization algorithm with 5-fold cross-validation. Each model was calibrated based on cross-validation performance and variance across iterations and then fit to the entire respective dataset (76 PTSD-positive, 76 PTSD-negative). We applied the trained models to an independent validation cohort to assess accuracy on unseen datasets. The top performing datasets from the validation cohort based on classification accuracy were metabolomics (65.2%) and protein expression (61.8%). We anticipate the candidate biomarkers identified in this and future studies will assist with the diagnosis of PTSD.