Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: A randomized controlled trial protocol.

BACKGROUND: The 2023 VA/DoD Clinical Practice Guideline for the Management of PTSD recommends individual, manualized trauma-focused such as Prolonged Exposure (PE) over pharmacologic interventions for the primary treatment of PTSD. Unfortunately, clinical trials of trauma-based therapies in the military and veteran population showed that 30% to 50% of patients did not demonstrate clinically meaningful symptom change. Ketamine, an FDA-approved anesthetic with potent non-competitive glutamatergic N-methyl-d-aspartate antagonistic properties, has demonstrated to enhance the recall of extinction learning and decrease fear renewal without interference of extinction training in preclinical studies. METHODS: We plan to conduct a single site RCT comparing three ketamine treatment vs. active placebo (midazolam) adjunct to PE therapy among Veterans with PTSD. Pharmacological phase will start simultaneously with PE session 1. Infusions will be administered 24 h. prior to PE session for the first 3 weeks. After PE is completed (session 10), patients will be assessed during a 3-month follow-up period at various time points. We estimate that out of 100 veterans, 80 will reach time point for primary outcome measure and will be considered for primary analysis. Secondary outcomes include severity of depression and anxiety scores, safety and tolerability of ketamine-enhanced PE therapy, cognitive performance during treatment and early improvement during PE related to the rate of dropouts during PE therapy. DISCUSSION: Results of the proposed RCT could provide scientific foundation to distinguish the essential components of this approach, enhance the methodology, elucidate the mechanisms involved, and identify sub-PTSD populations that most likely benefit from this intervention.

Serotonin Transporter (SLC6A4) and FK506-Binding Protein 5 (FKBP5) Genotype and Methylation Relationships with Response to Meditation in Veterans with PTSD.

Meditation-based interventions are novel and effective non-pharmacologic treatments for veterans with PTSD. We examined relationships between treatment response, early life trauma exposure, DNA polymorphisms, and methylation in the serotonin transporter (SLC6A4) and FK506-binding protein 5 (FKBP5) genes. DNA samples and clinical outcomes were examined in 72 veterans with PTSD who received meditation-based therapy in two separate studies of mindfulness-based stress reduction (MBSR) and Transcendental Meditation (TM). The PTSD Checklist was administered to assess symptoms at baseline and after 9 weeks of meditation intervention. We examined the SLC6A4 promoter (5HTTLPR_L/S insertion/deletion + rs25531_A/G) polymorphisms according to previously defined gene expression groups, and the FKBP5 variant rs1360780 previously associated with PTSD disease risk. Methylation for CpG sites of SLC6A4 (28 sites) and FKBP5 (45 sites) genes was quantified in DNA samples collected before and after treatment. The 5HTTLPR LALA high expression genotype was associated with greater symptom improvement in participants exposed to early life trauma (p = 0.015). Separately, pre to post-treatment change of DNA methylation in a group of nine FKBP5 CpG sites was associated with greater symptom improvement (OR = 2.8, 95% CI 1.1-7.1, p = 0.027). These findings build on a wealth of existing knowledge regarding epigenetic and genetic relationships with PTSD disease risk to highlight the potential importance of SLC6A4 and FKBP5 for treatment mechanisms and as biomarkers of symptom improvement.

Exploring Gender Differences in Veterans in a Secondary Analysis of a Randomized Controlled Trial of Mindfulness for Chronic Pain.

Background: Although studies have documented higher rates of chronic pain among women Veterans compared to men Veterans, there remains a lack of comprehensive information about potential contributors to these disparities. Materials and Methods: This study examined gender differences in chronic pain and its contributors among 419 men and 392 women Veterans, enrolled in a mindfulness trial for chronic pain. We conducted descriptive analyses summarizing distributions of baseline measures, obtained by survey and through the electronic health record. Comparisons between genders were conducted using chi-square tests for categorical variables and t-tests for continuous measures. Results: Compared to men, women Veterans were more likely to have chronic overlapping pain conditions and had higher levels of pain interference and intensity. Women had higher prevalence of psychiatric and sleep disorder diagnoses, greater levels of depression, anxiety, post-traumatic stress disorder, fatigue, sleep disturbance, stress and pain catastrophizing, and lower levels of pain self-efficacy and participation in social roles and activities. However, women were less likely to smoke or have a substance abuse disorder and used more nonpharmacological pain treatment modalities. Conclusion: Among Veterans seeking treatment for chronic pain, women differed from men in their type of pain, had greater pain intensity and interference, and had greater prevalence and higher levels of many known biopsychosocial contributors to pain. Results point to the need for pain treatment that addresses the comprehensive needs of women Veterans.Clinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020.

Treatment-related beliefs and reactions among trauma-focused therapy completers and discontinuers: A qualitative examination.

Prolonged exposure (PE) and cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) are effective, but some patients do not respond adequately, and dropout rates are high. Patients' beliefs about treatment and perceptions of treatment components influence treatment outcomes and may be amenable to change through intervention. The present study sought to identify beliefs and reactions to PE and CPT that differentiated completers who screened negative for a PTSD diagnosis after treatment (PTSD-), completers who screened positive for a PTSD diagnosis after treatment (PTSD+), and discontinuers who attended six or fewer sessions. Thematic analysis was used to identify themes in qualitative data collected via retrospective semistructured interviews with 51 completers (19 PTSD- after treatment, 32 PTSD+ after treatment) and 66 discontinuers of PE/CPT. Participants were demographically diverse veterans across service eras. Treatment-related beliefs and reactions differentiating these groups included perceived helpfulness of treatment, self-efficacy in engaging in treatment, anticipatory anxiety and concerns, interpretations of ongoing symptoms, and perceived consequences of treatment on functioning. Further, some patterns seemed to differ in early treatment sessions compared to during the active components of treatment. Findings point to potentially malleable targets that could be intervened upon to improve trauma-focused treatment outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The impact of substance use on posttraumatic stress disorder symptoms and treatment discontinuation.

This study examined the impact of ongoing substance use during posttraumatic stress disorder (PTSD) and substance use disorder (SUD) treatment on PTSD symptoms and treatment discontinuation. The study represents a secondary analysis of U.S. military veterans (N = 183) who participated in a randomized clinical trial for the treatment of both PTSD and SUD. Veterans mostly identified as Black (53.8%) or White (41.9%) and male (92.4%). Substance use, PTSD symptoms, and treatment discontinuation were measured at 4-week intervals throughout treatment. Predictors were the percentage of days with alcohol, cannabis, and other substance use (primarily cocaine and opioids) and the average number of alcoholic drinks per drinking day. Outcomes were PTSD symptoms and treatment discontinuation at concurrent and prospective assessments. Multilevel models accounted for the nested structure of the longitudinal data. Alcohol, cannabis, and other substance use did not predict PTSD symptoms or treatment discontinuation prospectively. Concurrently, we observed that as a participant's percentage of drinking days increased by 34.7% (i.e., 1 standard deviation), PTSD symptoms during the same period were 0.07 standard deviations higher (i.e., 1 point on the PCL), B = 0.03, p = .033. No other substances were related to PTSD symptoms concurrently. The findings demonstrate that PTSD symptoms improved regardless of substance use during exposure-based PTSD and SUD treatment, and treatment discontinuation was not associated with substance use. This study suggests that substance use during treatment cannot directly explain the poorer treatment outcomes observed in the literature on comorbid PTSD/SUD compared to PTSD-only populations.

Adaptation in Young Military Recruits: Protocol for the Advancing Research on Mechanisms of Resilience (ARMOR) Prospective Longitudinal Study.

BACKGROUND: Military services provide a unique opportunity for studying resilience, a dynamic process of successful adaptation (ie, doing well in terms of functioning and symptoms) in response to significant adversity. Despite the tremendous interest in positive adaptation among military service members, little is known about the processes underlying their resilience. Understanding the neurobiological, cognitive, and social mechanisms underlying adaptive functioning following military stressor exposure is essential for enhancing the resilience of military service members. OBJECTIVE: The primary objective of the Advancing Research on Mechanisms of Resilience (ARMOR) longitudinal study is to characterize the trajectories of positive adaptation among young military recruits in response to basic combat training (BCT), a well-defined, uniform, and 10-week period of intense stress (aim 1), and identify promotive and protective processes contributing to individual variations in resilience (aim 2). The secondary objective is to investigate the pathways by which neurobehavioral markers of self-regulation assessed using electroencephalography and magnetic resonance imaging contribute to adaptive trajectories (aim 3). METHODS: ARMOR is an ongoing, prospective longitudinal cohort study of young military recruits who recently joined the National Guard but have not yet shipped out for BCT. Participants (N=1201) are assessed at 5 time points over the initial >2 years of military service beginning before BCT (baseline) and followed up at 2 weeks and 6, 12, and 18 months after BCT. Participants complete web-based questionnaires assessing vulnerability and protective factors, mental health, and socioemotional functioning at each time point and a battery of neurocognitive tests at time 0. A subset of participants also complete structured diagnostic interviews and additional self-report measures and perform neurobehavioral tasks before and after BCT during electroencephalography sessions and before BCT only during magnetic resonance imaging sessions. RESULTS: This UG3/UH3 project was initially funded in August 2017, with the UG3 pilot work completed at the end of 2018. The UH3 phase of the project was funded in March 2019. Study enrollment for the UH3 phase began on April 14, 2019, and ended on October 16, 2021. A total of 1201 participants are enrolled in the study. Follow-up data collection for the UH3 phase is ongoing and projected to continue through February 2024. We will disseminate the findings through conferences, webinars, open access publications, and communications with participants and stakeholders. CONCLUSIONS: The ARMOR study provides a rich data set to identify the predictors and mechanisms of resilient and nonresilient outcomes in the context of military stressors, which are intended to empirically inform the development of prevention and intervention strategies to enhance the resilience of military trainees and potentially other young people facing significant life challenges. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51235.

Advancing Research on Mechanisms of Resilience (ARMOR) Prospective Longitudinal Study of Adaptation in Young Military Recruits: Protocol and rationale for methods and measures.

Background: Military service provides a unique opportunity for studying resilience, a dynamic process of successful adaptation (i.e., doing well in terms of functioning and symptoms) in response to significant adversity. Despite tremendous interest in positive adaptation among military service members, little is known about the processes underlying their resilience. Understanding neurobiological, cognitive, and social mechanisms underlying adaptive functioning following military stressor exposure is essential to enhance the resilience of military service members. Objectives: The primary objective of the Advancing Research on Mechanisms of Resilience (ARMOR) longitudinal study is to characterize trajectories of positive adaptation among young military recruits in response to Basic Combat Training (BCT), a well-defined, uniform, 10-week period of intense stress (Aim 1) and identify promotive and protective processes contributing to individual variations in resilience (Aim 2). The secondary objective is to investigate pathways by which neurobehavioral markers of self-regulation assessed by electroencephalography (EEG) and magnetic resonance imaging (MRI) contribute to adaptive trajectories (Aim 3). Methods: ARMOR is an ongoing, prospective longitudinal cohort study of young military recruits who recently joined the National Guard but have not yet shipped for BCT. Participants (N=1,201) are assessed at five timepoints over the initial 2+ years of military service beginning before BCT (baseline) and followed up at 2 weeks, 6, 12, and 18 months post-BCT. At each time point, participants complete online questionnaires assessing vulnerability and protective factors, mental health and social-emotional functioning, and, at Time 0 only, a battery of neurocognitive tests. A subset of participants also complete structured diagnostic interviews, additional self-report measures, and perform neurobehavioral tasks before and after BCT during EEG sessions, and, at pre-BCT only, during MRI sessions. Results: Study enrollment began April 14, 2019 and ended in October 16, 2021. A total of 1,201 participants are enrolled in the study (68.9% male; mean age = 18.9, SD = 3.0). Follow-up data-collection is ongoing and projected to continue through March 2024. We will disseminate findings through conferences, webinars, open access publications, and communications with participants and stakeholders. Conclusions: Results are expected to elucidate how young military recruits adapt to military stressors during the initial years of military service. Understanding positive adaptation of military recruits in the face of BCT has implications for developing prevention and intervention strategies to enhance resilience of military trainees and potentially other young people facing significant life challenges.

Feasibility of a prospective, longitudinal study of resilience among young military recruits with embedded laboratory sub-study: the ARMOR pilot trial.

Background: Multilevel, longitudinal studies are integral to resilience research; however, they are costly and present unique methodological challenges. The objective of this study was to examine the feasibility of study methods (recruitment, retention, data collection) for a large-scale prospective, longitudinal study of resilience among young National Guard recruits. Methods: This feasibility trial used a pre-test/post-test design with embedded laboratory sub-study. Participants were young military recruits who had recently enlisted in the Army National Guard and had not yet shipped to Basic Combat Training (BCT). Recruitment and baseline data collection (Time 1), which included a battery of computerized self-report measures and neurocognitive tests, were conducted at local armories. Participants completed an online follow-up (Time 2) survey outside of drill training after returning from BCT. A subset of participants was recruited to complete extensive laboratory procedures pre-and post-BCT, including clinical interview, additional self-report measures, and performance on a series of neurobehavioral tasks during electroencephalogram recordings and, at pre-BCT only, magnetic resonances imaging. Feasibility outcomes assessed our ability to recruit, retain, and collect data from participants. Analysis of outcomes was based on descriptive statistics and evaluation of the feasibility of the larger study was based on pre-determined go/no go progression criteria. Results: All pre-determined progression criteria were met. A total of 102 (97.1%) of eligible military service members consented to participate. Of these, 73 (73.7%) completed the Time 2 survey. Of the 24 participants approached, 14 agreed to participate in the laboratory sub-study, 13 completed follow-up laboratory visits. Overall, completion of online surveys and laboratory tasks was excellent. However, participants had difficulties completing online surveys during BCT and the computerized neurocognitive testing battery at Time 2. Conclusions: Study methods were feasible, and all predetermined criteria for progression to the large-scale longitudinal study were met. Some minor protocol adaptations were identified from this feasibility study. Lessons learned and recommendations for future research are discussed.

A dynamic, multilevel approach to conceptualising and designing resilience research in the context of military stress.

Challenges in conceptualising resilience have impeded advancements in resilience science. In response, the National Institutes of Health (NIH) developed a general framework for harmonising the conceptualisation of resilience as a dynamic process determined by multiple systems and levels of analysis. Consistent with the NIH Resilience Framework, this paper presents a conceptual model of resilience applied to military service members. This model encompasses four core components necessary for resilience research: (1) the presence of significant challenge, (2) successful adaptation in response to the challenge, (3) the capacity for resilience (i.e., protective factors), and (4) the processes (i.e., mechanisms) by which protective factors exert positive effects on an individual's response. Guided by this conceptual model, we outline key methodological recommendations to advance resilience research and illustrate each using the Advancing Research on Mechanisms of Resilience study as an exemplar. We emphasise the need for future research to examine resilience as a dynamic process and apply a multilevel approach. We hope to provide a basic road map to those interested in improving the rigour of future research on resilience in a military context, the results of which can inform the development of interventions.

The role of symptom accommodation in trauma-focused treatment engagement and response.

Although trauma-focused treatments (TFTs) are generally effective, not all patients improve. Symptom accommodation (i.e., altering one's behavior in response to another's symptoms) by loved ones may be particularly relevant to TFT treatment response and engagement. We examined the role of symptom accommodation by support persons (SPs) in veterans' PTSD treatment response, including the mediating role of treatment engagement and the moderating role of relationship strain. Veterans engaging in prolonged exposure or cognitive processing therapy and a loved one (N = 172 dyads) were sampled at two time points approximately four months apart. Measures of treatment engagement (i.e., highest session completed from the treatment protocol and homework completion) were obtained from hospital records. We found that relationship strain moderated the effect of symptom accommodation on treatment response, ∆R2 = .02. Specifically, Time 1 (T1) accommodation predicted poorer treatment response (i.e., Time 2 [T2] PTSD symptom severity, controlling for T1 symptoms) among veterans who reported below-average relationship strain only. Additionally, symptom accommodation was indirectly related to treatment response such that T1 accommodation predicted higher T2 PTSD symptom severity specifically through reduced homework completion, ß = .01. The findings suggest that attending to accommodating behaviors of veterans' supportive partners may be an important way to boost both engagement in and response to TFTs for PTSD.

Provider perceptions of their patients' dropout from trauma-focused therapy for PTSD in the U.S. Veterans Health Administration.

OBJECTIVE: Many patients who initiate prolonged exposure (PE) and cognitive processing therapy (CPT) do not complete a full course, although little is known about how providers view PE and CPT dropout among their own patients. METHOD: Semistructured interviews were conducted with providers (n = 29) in the Veterans Health Administration to understand each provider's experience of dropout by a specific patient whom they treated using PE or CPT. Content analysis was used to categorize perceptions of dropout as negative, somewhat negative, or not negative. Themes associated with somewhat or not negative views of dropout were identified via inductive coding. RESULTS: Fourteen percent of providers viewed their patient's dropout from PE or CPT as wholly negative, 38% as somewhat negative, and 48% as not a negative outcome. Themes associated with viewing dropout as something other than wholly negative included belief that the patient would not benefit from treatment if they were not ready, the importance of maintaining the therapeutic relationship, the view that trauma-focused therapy was not what the patient needed or that the patient could benefit from other approaches, the impression that the patient had made some gains, and that patients are responsible for treatment engagement and have the right to disengage. CONCLUSIONS: Providers' perceptions of dropout from PE or CPT for individual patients were rarely viewed as entirely negative. Research is needed to help providers determine when patient dropout is an undesirable outcome and when efforts to reengage patients in trauma-focused treatment are warranted. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The role of the MMPI-2-Restructured Form (MMPI-2-RF) in predicting and better understanding engagement in posttraumatic stress disorder treatment.

The ability of Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008/2011) scores to predict treatment engagement in veterans referred for empirically supported treatments for symptoms of Posttraumatic Stress Disorder (PTSD) was examined. Early withdrawal from treatment and process factors, such as adherence and therapy session attendance, were examined in 100 veterans seeking treatment for trauma-related symptoms who were referred to a Veterans Health Administration medical center's tertiary care clinic for Prolonged Exposure (PE) or Cognitive Processing Therapy (CPT). Veterans who scored higher on MMPI-2-RF scales associated with emotional/internalizing problems were more likely to be referred to PE or CPT, but individuals with the highest scores on those scales were also more likely to withdraw before completing treatment. These findings suggest Harkness and Lilienfeld's (1997) call to use personality assessment to guide treatment planning holds promise to better understand treatment engagement. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Making sense of poor adherence in PTSD treatment from the perspectives of veterans and their therapists.

OBJECTIVE: Dropout rates from trauma-focused PTSD treatments (TFTs) in VA clinics are particularly high. We conducted in-depth qualitative interviews with 29 veterans and their therapists to better understand this phenomenon. METHOD: Participants were part of a multisite, mixed-methods study of TFT adherence in VA clinics. Veterans were eligible for interviews if they exhibited poor TFT adherence and screened positive for PTSD in follow-up surveys. Interviews were analyzed using qualitative dyadic analysis approaches. RESULTS: Therapists relied on stereotypes of poor adherence to understand veterans' experiences and were missing information critical to helping veterans succeed. Veterans misunderstood aspects of the therapy and struggled in ways they inadequately expressed to therapists. Therapist attempts at course corrections were poorly matched to veterans' needs. Many dyads reported difficulties in their therapeutic relationships. Veterans reported invalidating experiences that were not prominent in therapists' interviews. CONCLUSIONS: Future work is needed to test hypotheses generated and find effective ways to help veterans fully engage in TFTs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Comparative effectiveness of trauma-focused and non-trauma-focused psychotherapy for PTSD among veterans with comorbid substance use disorders: Protocol & rationale for a randomized clinical trial.

BACKGROUND: Co-occurrence of posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) is common and concurrent treatment is recommended. Relatively little is known about which evidence-based psychotherapies for PTSD are most effective for patients with varying substance use profiles. We aim to examine the comparative effectiveness of trauma-focused therapy (TFT) and non-trauma-focused therapy (NTFT) among Veterans with PTSD and SUD. TFT has been found to be effective among those with PTSD/SUD, though effects are smaller and rates of treatment non-completion are higher than in those without SUD. NTFTs suggested for the treatment of PTSD, such as Present Centered Therapy, (PCT) have not been examined among those with co-occurring SUD, despite lower rates of treatment dropout. We will also examine the comparative effectiveness of TFT and NTFT for patients with varying SUD severity, type of substances used, and patient treatment preference. METHOD: 420 Veterans with PTSD and SUD will be randomized in a prospective, pragmatic comparative effectiveness trial at 14 Veterans Health Administration facilities. Participants will receive either TFT (Prolonged Exposure or Cognitive Processing Therapy) or NTFT (PCT) after enrolling in concurrent SUD treatment-as-usual. Assessments will occur at baseline, posttreatment, 3- and 6 -months posttreatment. Main outcomes are PTSD symptom severity and PTSD treatment dropout. Clinician, patient, and leadership stakeholder panels advise study activities, and a process evaluation will identify strategies to enhance the implementation of evidence-based PTSD treatments in SUD care settings. CONCLUSIONS: Results will provide critical information to guide clinicians when recommending PTSD treatments to patients with comorbid SUD. CLINICALTRIALS: gov Identifier: NCT04581434.

Amputation-specific and generic correlates of participation among Veterans with lower limb amputation.

Participation in valued interpersonal and community activities is a key component of rehabilitation for Veterans with amputation. The purpose of this study was to identify specific factors that promote or inhibit participation to inform development of interventions that may facilitate participation in desired life activities. A convenience sample of 408 Veterans with at least one lower limb amputation and who had received outpatient care from the Regional Amputation Center (RAC) completed a mailed survey. Participation was measured using the Community Participation Indicators (CPI) Importance, Control, and Frequency scales and the Patient Reported Outcome Measurement Information System (PROMIS) Ability to Participate in Social Roles and Satisfaction with Social Participation scales. Multiple imputation procedures were used to address missing data. Correlates of participation were examined through multiple linear regression. A total of 235 participants completed the survey, a response rate of 58%. Levels of participation, measured with the PROMIS instruments, were 43.2 (SD = 8.1) for Ability and 46.4 (SD = 8.6) for Satisfaction. Regression analyses found robust amputation-specific correlates for participation, including body image and balance confidence. Generic (non-amputation specific) correlates for participation included depression and pain interference. Development of treatment approaches and devices that can address body image, balance confidence, pain, and mental health concerns such as depression have the potential to enhance the participation and rehabilitation of Veterans with lower limb amputation.

Divergent experiences of U.S. veterans who did and did not complete trauma-focused therapies for PTSD: A national qualitative study of treatment dropout.

Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT) are first-line treatments for posttraumatic stress disorder (PTSD) and have been disseminated throughout the U.S. Veterans Health Administration. Treatment non-completion is common and lessens clinical effectiveness; however, prior work has failed to identify factors consistently associated with non-completion. Semi-structured interviews were conducted with a national sample of veterans who recently completed (n = 60) or did not complete (n = 66) PE or CPT. Non-completer interviews focused on factors that contributed to veterans' decisions to drop out and efforts undertaken to complete PE/CPT. Completer interviews focused on challenges faced in completing treatment and facilitators of completion. Transcripts were coded using a mixed deductive/inductive approach; constant comparison was used to identify differences between completers and non-completers. Completers and non-completers differed in the extent of treatment-specific therapist support received, therapists' flexibility in treatment delivery, the type of encouragement offered by the care team and social supports, their interpretation of symptom worsening, the perceived impact of treatment on functioning, and the impact of stressors on their treatment engagement. Treatment-specific therapist support, more patient-centered and flexible treatment delivery, leveraging the full care team, and addressing functional concerns are potential targets for PE and CPT engagement interventions.

Inconsistent Reporting of Adverse Life Events Is Predicted by Current Internalizing Distress Among Military Service Members.

INTRODUCTION: Accurate measurement of adverse life events is critical for understanding the effects of stressors on health outcomes. However, much of this research uses cross-sectional designs and self-report years after the events take place. The reliability of this retrospective reporting and the individual difference factors associated with inconsistent recall over time are not frequently addressed, especially among military service members. MATERIALS AND METHODS: A longitudinal cohort of National Guard service members (n = 801) completed the Deployment Risk and Resilience Inventory-2 Prior Stressors scale and several measures of general well-being, including anxious depressive symptomatology, personal functioning, perceived social support, and overall health at two time points (before and after completion of basic combat training; median 11-month interval). RESULTS: Consistency in reporting the life event items ranged from 69.5% to 99.7%, with an overall Cohen's kappa coefficient of 0.215 for the scale, indicating minimal agreement. Lower well-being scores at Time 1 independently predicted yes-to-no changes in responding, whereas lower well-being scores at Time 2 independently predicted no-to-yes changes in responding. Follow-up mediations were conducted using study measures available only at Time 2. For all study measures, Time 2 well-being independently predicted changes from no-to-yes responding by way of indirect effects through self-reported non-specific internalizing distress and arousal. CONCLUSIONS: These findings highlight the confounding effects of fluctuations in current emotional distress on past stressor recall. There is a need for additional caution regarding the use of retrospective self-report of adverse life events in research and clinical practice and greater consideration of current psychological distress at the time of measurement completion.

Can families help veterans get more from PTSD treatment? A randomized clinical trial examining Prolonged Exposure with and without family involvement.

BACKGROUND: Posttraumatic stress disorder occurs in as many as one in five combat veterans and is associated with a host of negative, long-term consequences to the individual, their families, and society at large. Trauma-focused treatments, such as Prolonged Exposure, result in clinically significant symptom relief for many. Adherence to these treatments (i.e., session attendance and homework compliance) is vital to ensuring recovery but can be challenging for patients. Engaging families in veterans' treatment could prove to be an effective strategy for promoting treatment adherence while also addressing long-standing calls for better family inclusion in treatment for posttraumatic stress disorder. This paper describes the methods of a pragmatic randomized controlled trial designed to evaluate if family inclusion in Prolonged Exposure can improve treatment adherence. METHODS: One hundred fifty-six veterans, with clinically significant symptoms of posttraumatic stress disorder, will be randomized to receive either standard Prolonged Exposure or Prolonged Exposure enhanced through family inclusion (Family-Supported Prolonged Exposure) across three different VA facilities. Our primary outcomes are session attendance and homework compliance. Secondary outcomes include posttraumatic stress disorder symptom severity, depression, quality of life, and relationship functioning. The study includes a concurrent process evaluation to identify potential implementation facilitators and barriers to family involvement in Prolonged Exposure within VA. DISCUSSION: While the importance of family involvement in posttraumatic stress disorder treatment is non-controversial, there is no evidence base supporting best practices on how to integrate families into PE or any other individually focused trauma-focused treatments for posttraumatic stress disorder. This study is an important step in addressing this gap, contributing to the literature for both retention and family involvement in trauma-focused treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT03256227 . Registered on August 21, 2017.

Biomarker Response to Mindfulness Intervention in Veterans Diagnosed with Post-traumatic Stress Disorder.

Objectives: This study evaluates the effects of treatment with mindfulness-based stress reduction (MBSR) compared to the active control, present-centered group therapy (PCGT), on morning plasma cortisol, interleukin-6 (IL-6), and C-reactive protein (CRP) in veterans diagnosed with post-traumatic stress disorder (PTSD). Methods: In a post hoc exploratory analysis, we pooled biomarkers and clinical outcomes of mindfulness, PTSD, and depression from two randomized controlled trials comparing MBSR (n = 104) to PCGT (n = 106) in U.S. military veterans diagnosed with PTSD. Linear mixed-effects modeling was used to evaluate associations between changes in biomarkers and clinical outcomes from baseline to 9-week primary endpoint and 16-week follow-up endpoint. Results: Cortisol levels were inversely related to self-reported PTSD symptoms at baseline (p = 0.02). Cortisol increased from baseline to 9-week endpoint for both groups, but significantly less so in the MBSR group compared to PCGT group (mean difference 1.69 ± 0.8 SE; p = 0.035). Changes in IL-6 and CRP did not differ between groups at either baseline or week 9. From baseline to week 9, increased mindfulness was significantly associated with increased cortisol (p = 0.02) and decreased PTSD and depression severity (p < 0.01). Increased IL-6 and CRP were significantly associated with decreased PTSD severity (p < 0.05), but not depression. Pooled analysis corroborated earlier findings that MBSR is significantly better than PCGT in improving clinical outcomes. Increased mindfulness was strongly associated with improved symptoms. Conclusions: Increased mindfulness is associated with a recalibration of cortisol levels which may be indicative of therapeutic response, especially in patients with lower baseline cortisol. Furthermore, mindfulness-based practices improve symptoms of PTSD and depression in a significant correlation with self-reported levels of mindfulness. Clinical Trial Registration clinicaltrialsgov: NCT01532999 and NCT01548742.

"It leaves me very skeptical" messaging in marketing prolonged exposure and cognitive processing therapy to veterans with PTSD.

OBJECTIVE: Direct-to-consumer marketing has the potential to increase demand for specific treatments, but little is known about how to best market evidence-based psychotherapies to veterans with posttraumatic stress disorder (PTSD). The objective of this study was to gain an understanding of marketing messages that may impact veteran demand for prolonged exposure (PE) and cognitive processing therapy (CPT). METHOD: Veterans (n = 31) with full or subthreshold PTSD participated in semistructured interviews that queried attitudes about PTSD and recovery, current knowledge of PE and CPT, and reactions to existing educational materials. A 2-stage qualitative coding and analytic strategy was used to identify primary themes related to the marketing of PE and CPT. RESULTS: Veterans viewed the treatments' effectiveness as their primary selling point but questioned the credibility of improvement descriptions that didn't fit with their experiences or beliefs about PTSD. Participants had difficulties distinguishing CPT from non-trauma-focused approaches in which they had previously participated, leading to skepticism about promised treatment effects and decreased interest. Without targeting, women veterans assumed information regarding PTSD treatment options applied only to men. CONCLUSIONS: Examination of the impact of a direct-to-consumer marketing campaign including these messages on PE and CPT demand is needed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).