Combat-related Posttraumatic Stress Disorder Research Articles

PSTD Treatment of Joint Forces Operation Combatants: A Case Study.

The participation of military personnel in operations like the Anti-Terrorist Operation (ATO)/Joint Forces Operations (JFO) can lead to significant psychological trauma, potentially resulting in posttraumatic stress disorder (PTSD). Understanding the effectiveness of psychotherapy in treating PTSD among ATO/JFO participants is crucial given its profound impact on personal relationships, life scenarios, and overall well-being. This study evaluates how acceptance and commitment therapy can alleviate PTSD symptoms and enhance well-being in Ukrainian military personnel with combat-related PTSD. The main research method was a psychological experiment, and the case study method was used as an auxiliary research method. The study revealed the following: combatants in the ATO/JFO who have been diagnosed with PTSD should be classified as persons with disabilities due to certain limitations in their life activities, namely, the inability to control their behavior, and difficulties in work and communication. This study proves that cognitive-behavioral psychotherapy has a clear advantage in overcoming PTSD in the military, as it allows transforming psychological trauma into posttraumatic growth. Attachment and acceptance therapy, a form of behavioral therapy, has emerged as one of the most effective treatments for PTSD. It focuses on diagnosing and addressing the psychological consequences of war by analyzing the connections among cognition, affect, and behavior. Given the protracted nature of PTSD, the practical significance of the study is to develop effective psychotherapeutic interventions for the expected recovery of ATO/JFO participants affected by combat operations.

Psychometric properties of the 23-Item Clinician Administered Dissociative States Scale (CADSS) in a psychological trauma population

ObjectiveDissociative symptoms are both a pathological consequence of exposure to psychological trauma as well as a side effect of N-methyl-d-aspartate (NMDA) receptor antagonist medications; therefore, accurate and valid assessment of these symptoms is important. The psychometric properties of the 23-item Clinician Administered Dissociative States Scale (CADSS) have been characterized in the ketamine and esketamine literatures. Here, we examine its performance in a sample with and without posttraumatic stress disorder (PTSD) and a history of exposure to psychological trauma. MethodsParticipants with a history of psychological trauma with (N = 148) and without (N = 100) the diagnosis of PTSD and healthy participants without a psychiatric disorder or history of trauma (N = 28) were assessed with the 23-item CADSS and other psychometric and neuropsychological assessments. Analyses were performed to examine internal consistency, convergent and discriminant validity, factor structure, differential performance in populations reported to be more or less likely to report dissociative symptoms (e.g., patients with and without PTSD), and sensitivity to change resulting from exposure to trauma-related sights and sounds. ResultsThe 23-item CADSS was found to have high internal consistency (Cronbach's alpha 0.91) and a single-factor structure. CADSS total scores in trauma-exposed participants with PTSD were higher than those in trauma-exposed participants without PTSD and non-traumatized non-PTSD participants. Finally, veterans with Iraq combat-related PTSD showed a significant increase in CADSS total score after exposure to combat-related slides and sounds. ConclusionThe 23-item CADSS, already validated as a tool to measure dissociation related to administration of NMDA receptor antagonist medication, performs in a reliable and valid manner in the assessment of dissociation in psychologically traumatized participants.

FLI1 in PBMCs contributes to elevated inflammation in combat-related posttraumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with significant public health implications that arise following exposure to traumatic events. Recent studies highlight the involvement of immune dysregulation in PTSD, characterized by elevated inflammatory markers. However, the precise mechanisms underlying this immune imbalance remain unclear. Previous research has implicated friend leukemia virus integration 1 (FLI1), an erythroblast transformation-specific (ETS) transcription factor, in inflammatory responses in sepsis and Alzheimer's disease. Elevated FLI1 levels in peripheral blood mononuclear cells (PBMCs) have been linked to lupus severity. Yet, FLI1's role in PTSD-related inflammation remains unexplored. In our study, PBMCs were collected from Veterans with and without PTSD. We found significantly increased FLI1 expression in PBMCs from PTSD-afflicted Veterans, particularly in CD4+ T cells, with no notable changes in CD8+ T cells. Stimulation with LPS led to heightened FLI1 expression and elevated levels of inflammatory cytokines IL-6 and IFNγ in PTSD PBMCs compared to controls. Knockdown of FLI1 using Gapmers in PTSD PBMCs resulted in a marked reduction in inflammatory cytokine levels, restoring them to control group levels. Additionally, co-culturing PBMCs from both control and PTSD Veterans with the human brain microglia cell line HMC3 revealed increased inflammatory mediator levels in HMC3. Remarkably, HMC3 cells co-cultured with PTSD PBMCs treated with FLI1 Gapmers exhibited significantly lower inflammatory mediator levels compared to control Gapmer-treated PTSD PBMCs. These findings suggest that suppressing FLI1 may rebalance immune activity in PBMCs and mitigate microglial activation in the brain. Such insights could provide novel therapeutic strategies for PTSD.

Potential Neurophysiological Markers of Combat-Related Post-Traumatic Stress Disorder: A Cross-Sectional Diagnostic Study.

Studies suggest that the components of brain-evoked potentials (EPs) may serve as biomarkers of the post-traumatic stress disorder (PTSD) caused by participation in combat operations; however, to date, research remains fragmented, with no studies that have attempted to combine different paradigms. In addition, the mismatch negativity component has not been studied in a Russian sample of veterans with PTSD. To identify objective neurophysiological markers of combat-related PTSD using the method of auditory-evoked potentials in active and passive listening paradigms. The study included a recording of auditory EPs in an oddball paradigm in three settings: 1) directed attention to auditory stimuli, 2) passive listening while viewing a neutral video sequence, and 3) viewing a video sequence associated with a traumatic event. Combatants diagnosed with PTSD (18 people) were compared with mentally healthy civilian volunteers (22 people). An increase in the latency period of the early components of auditory EP (N100 and P200), an increase in the amplitude of the P200 component to a deviant stimulus, and a decrease to a standard one in the active listening paradigm were established in the PTSD group. There were no significant differences in the parameters of the P300 component. The characteristics of mismatch negativity in the passive paradigm were revealed: an increase in the phenomenon amplitude, both when shown a video sequence associated with a traumatic event and when shown a neutral video sequence. A binary logistic regression model constructed using the selected parameters showed that the identified characteristics can potentially be considered as diagnostic markers of PTSD in combatants, as the classification accuracy stood at 87% (sensitivity - 81%, specificity - 91%). Potential neurophysiological markers of PTSD are the following: the amplitude and latency of early components of auditory EPs in the paradigm of directed attention to stimuli and the amplitude of mismatch negativity during passive attention.

Структура временной перспективы участников боевых действий с ампутацией конечностей

The relevance of the reported study results from the need to clearly define the target of psychological impact in combatants with amputated limbs. The time perspective being an integral characteristic ensures the life experience integrity: all life events are intertwined within the boundaries of the past, present and future. The study was aimed to assess the time perspective structure in combatants with amputated limbs. The sample consisted of 78 males aged 20–53 years, who had combat experience and underwent treatment or rehabilitation after getting injured. The study involved the use of the Mississippi Scale for Combat-Related PostTraumatic Stress Disorder, Zimbardo Time Perspective Inventory, method for event-based reconstruction of a person’s time perspective by V.B. Nikishina and E.A. Petrash, SR-45 method by P.I. Yunatskevich, infantilism inventory by A.A. Seregin. The factor structure of time perspective in combatants with amputated upper limbs includes the factor of non-reflexive future, factor of limited time perspective, and the situational and behavioral risk factor. In cases of amputated lower limbs, the situational future factor, past orientation factor, and situational and behavioral risk factor are represented. In cases of no amputated limbs, the combatants’ time perspective structure includes the factor of reflexive future perspective, factor of limited present fatalistic, and past orientation factor.

Affect labeling: a promising new neuroscience-based approach to treating combat-related PTSD in veterans.

A significant portion of individuals exposed to combat-related trauma will develop posttraumatic stress disorder (PTSD), a severe, debilitating disorder with adverse impacts on both mental and physical functioning. Current treatments are effective for many individuals, however, there is a need for new treatment approaches to improve outcomes in PTSD and address the many existing barriers to seeking or completing treatment. In this open trial pilot study, we tested a novel, brief, computer-based intervention for PTSD utilizing "affect labeling" that was inspired by recent advances in neuroscience with U.S. veterans. As expected, pre-intervention clinical and fMRI neuroimaging data indicated that U.S. veterans with combat-related PTSD (N = 20) had significantly higher PTSD symptoms, depression symptoms, and amygdala reactivity to trauma cues than trauma-exposed healthy control veterans (N = 20). Veterans with PTSD who completed the affect labeling intervention (N = 13) evidenced reduced PTSD symptoms and these reductions were correlated with reductions in amygdala reactivity. Results from this initial proof-of-concept study are intriguing and suggest that affect labeling training offers significant potential as a novel, cost-effective, computer-based intervention for PTSD. Implications and next steps for further developing affect labeling interventions for PTSD are discussed. https://clinicaltrials.gov/, identifier NCT05924399.

PECULIARITIES OF ADAPTATION AND COURSE OF POST-TRAUMATIC STRESS DISORDER IN SERVICEMEN DEPLOYED TO INTENSE COMBAT ZONES

In the context of war, post-traumatic stress disorder (PTSD) emerges as one of the most prevalent psychological conditions, particularly among military personnel deployed in combat zones. The primary triggers for PTSD in military personnel often include the loss of comrades or the necessity to use lethal weapons, resulting in significant consequences. For PTSD to manifest, individuals must undergo a traumatic experience that exceeds normal human stress levels and leads to distress. The aim of this study is to investigate the course of PTSD in military personnel who have been exposed to intense combat operations and to explore their maladaptive manifestations. The study comprised 38 patients diagnosed with PTSD (F43.1) according to the ICD-10, who received treatment at the Regional Mental Health Care Institution for the Protection of the Armed Forces. All patients provided informed consent to participate in the study. A structured clinical diagnostic interview known as CAPS-DX was applied in this study. Developed based on the DSM-IV, this interview assesses the symptoms of posttraumatic stress disorder (PTSD), the duration of the disorder, and the degree of impairment of social functioning. The CAPS-DX scale provided insights into the presence of PTSD symptoms both currently and throughout the individual's life following psychotrauma. To diagnose psychosocial maladjustment and its characteristics, we employed the Psychosocial Maladjustment Scale by L. Herasymenko (2018). Clinical and anamnestic examinations revealed that 86% of servicemen had experienced multiple traumatic events, indicating a history of several psychotraumas. The study identified that the primary psychopathological manifestations of PTSD did not differ significantly from the traditional course of the disorder, but they were more intense and pronounced in this group of servicemen. The study has demonstrated that servicemen with combat experience and PTSD exhibited reduced levels of psychosocial adaptation. Their adaptive resources and capabilities, as well as their neuropsychological stability, were significantly diminished, along with a decrease in their communication abilities. Based on the overall level and quality of social and psychological adaptation, three levels of adaptation/maladaptation were distinguished among servicemen with combat-related PTSD: sufficient, partial, or maladaptation. It should be noted that the levels of adaptation were correlated with the severity of anxiety. Servicemen with sufficient adaptation typically exhibited low levels of anxiety, while those with partial adaptation showed an average level, and those with maladaptation displayed high levels of anxiety. The study revealed a spectrum of psychopathological manifestations in servicemen who were in the combat zone, ranging from semiotic complexes resembling panic attacks to psychogenic catalepsy. Furthermore, it was found that servicemen with combat experience and post-traumatic stress disorder had reduced levels of psychosocial adaptation, which correlated with the severity of anxiety.

A pilot study of stellate ganglion block paired with exposure therapy: Feasibility and acceptability in combat veterans with posttraumatic stress disorder.

There is growing evidence that stellate ganglion block (SGB) combined with trauma-focused therapy may help veterans with posttraumatic stress disorder (PTSD) whose symptoms have not responded to traditional treatments. By combining SGB with in vivo exposure, veterans may be more able to fully engage in treatment and see improvement in their overall functioning. The primary aim of this project was to conduct a nonrandomized pilot trial on the feasibility and acceptability of delivering SGB paired with individual psychotherapy to veterans with combat-related PTSD. Eligible veterans (N = 14) constructed a hierarchy of in vivo exposure exercises, received the SGB procedure, and attended four additional weekly psychotherapy sessions with a focus on exposure exercises. Participants completed measures at baseline, weekly during treatment, and follow-up assessments immediately posttreatment and 1-month later. The recruitment target was easily met, session attendance was strong, and dropout was relatively low (21.4%). SGB was well tolerated with only mild, transient side effects. Participants reported satisfaction with the treatment they received as measured by the Client Satisfaction Questionnaire (M = 28.8). Paired t test analyses revealed a significant decrease in PTSD symptoms as measured by the PTSD Checklist for DSM-5. We also observed a significant reduction in PTSD symptoms as measured by the Clinician-Administered PTSD Scale for DSM-5 in mixed models, F(2, 13) = 8.68, p = .004. There were no significant improvements in psychosocial functioning or quality of life. SGB paired with psychotherapy is feasible and acceptable to veterans and holds promise for symptom reduction among veterans with combat-related PTSD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Case report: the addition of olfaction to virtual reality enhanced exposure therapy for PTSD

Posttraumatic stress disorder (PTSD) occurs in approximately 20% of individuals following exposure to a potentially traumatic event. Re-experiencing in the form of intrusive memories is a hallmark feature, and often includes sensory elements, including odor. A small body of studies have examined the relationship between PTSD and odor evoked memories. Patients avoid smells that remind them of their traumatic event, and odors are known triggers for intrusive memories and distress. PTSD is associated with higher ratings of odor intensity and unpleasantness however accuracy of odor detection is often impaired. It has been suggested that adding trauma-related odors will enhance treatment, however little data exists. This case study illustrates the addition of trauma specific olfaction in Virtual Reality (VR) enhanced exposure therapy for combat related PTSD. Treatment was successful, the patient no longer met criteria for PTSD at the end of treatment, and self-report symptoms scores indicated clinically significant reductions. The patient indicated at the end of treatment that he would not have been helped had the therapy not used VR, and the addition of odors helped him process the traumatic memories. Future research should assess the addition of olfaction in a systematic way, in order to assess its specific impact in the effectiveness of PTSD treatment.

Circulating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSD

Circulating cell-free mitochondrial DNA (ccf-mtDNA) is a biomarker of cellular injury or cellular stress and is a potential novel biomarker of psychological stress and of various brain, somatic, and psychiatric disorders. No studies have yet analyzed ccf-mtDNA levels in post-traumatic stress disorder (PTSD), despite evidence of mitochondrial dysfunction in this condition. In the current study, we compared plasma ccf-mtDNA levels in combat trauma-exposed male veterans with PTSD (n = 111) with those who did not develop PTSD (n = 121) and also investigated the relationship between ccf mt-DNA levels and glucocorticoid sensitivity. In unadjusted analyses, ccf-mtDNA levels did not differ significantly between the PTSD and non-PTSD groups (t = 1.312, p = 0.191, Cohen’s d = 0.172). In a sensitivity analysis excluding participants with diabetes and those using antidepressant medication and controlling for age, the PTSD group had lower ccf-mtDNA levels than did the non-PTSD group (F(1, 179) = 5.971, p = 0.016, partial η2 = 0.033). Across the entire sample, ccf-mtDNA levels were negatively correlated with post-dexamethasone adrenocorticotropic hormone (ACTH) decline (r = −0.171, p = 0.020) and cortisol decline (r = −0.149, p = 0.034) (viz., greater ACTH and cortisol suppression was associated with lower ccf-mtDNA levels) both with and without controlling for age, antidepressant status and diabetes status. Ccf-mtDNA levels were also significantly positively associated with IC50-DEX (the concentration of dexamethasone at which 50% of lysozyme activity is inhibited), a measure of lymphocyte glucocorticoid sensitivity, after controlling for age, antidepressant status, and diabetes status (β = 0.142, p = 0.038), suggesting that increased lymphocyte glucocorticoid sensitivity is associated with lower ccf-mtDNA levels. Although no overall group differences were found in unadjusted analyses, excluding subjects with diabetes and those taking antidepressants, which may affect ccf-mtDNA levels, as well as controlling for age, revealed decreased ccf-mtDNA levels in PTSD. In both adjusted and unadjusted analyses, low ccf-mtDNA levels were associated with relatively increased glucocorticoid sensitivity, often reported in PTSD, suggesting a link between mitochondrial and glucocorticoid-related abnormalities in PTSD.

Massed cognitive processing therapy for combat-related posttraumatic stress disorder: Study design and methodology of a non-inferiority randomized controlled trial

BackgroundPosttraumatic stress disorder (PTSD) is prevalent among military personnel. Cognitive processing therapy (CPT) is identified as one of the most effective treatments for PTSD, although smaller effects have been found in military populations. High rates of dropout from treatment may contribute to reduced efficacy, and military personnel may face unique barriers to treatment completion. One method of improving efficacy may be to reduce dropout by decreasing the time required to receive a full dose of treatment. This paper describes the design and methodology of the first randomized clinical trial testing whether CPT delivered in an intensive format is non-inferior to standard delivery of CPT. MethodParticipants are 140 active duty service members randomized to receive CPT in a 5-day combined group and individual intensive outpatient format (MCPT) or standard CPT (delivered individually twice weekly over 6 weeks). Participants are assessed at baseline, and 1 month, 4 months, and 1 year following the conclusion of the therapy. Reduction in PTSD symptomatology is the primary outcome of interest. Secondary outcomes include comorbid psychological symptoms, health, and functioning. A secondary objective is to examine predictors of treatment outcome to determine which service members benefit most from which treatment modality. ConclusionIf determined to be non-inferior, MCPT would provide an efficient and accessible modality of evidence-based PTSD treatment. This therapy format would improve access to care by reducing the amount of time required for treatment and improving symptoms and functioning more rapidly, thereby minimizing interference with work-related activities and disruption to the mission.

Daily exposure to combat-related cues and posttraumatic stress symptoms among veterans: Moderating effects of peri- and postdeployment experiences.

One of the central symptoms of posttraumatic stress disorder (PTSD) is a heightened reactivity to trauma cues. The current study used experience sampling to investigate the associations between exposure to combat-related cues and PTSD symptoms in 93 U.S. veterans who served in support of recent military operations in Afghanistan and Iraq. We also examined the effects of peri- and postdeployment factors, including exposure to combat, unit support during deployment, and postdeployment social support on PTSD. Participants completed eight brief random surveys daily for 2 weeks using palmtop computers. The results indicated that more daytime exposure to trauma cues was associated with experiencing more PTSD symptoms at the within-person level, B = 3.18. At the between-person level, combat exposure, B = 4.20, was associated with more PTSD symptoms, whereas unit support, B = -0.89, was associated with experiencing fewer symptoms. At the cross-level interaction, unit support, B = -0.80, moderated the association between trauma cue exposure and PTSD symptom count. Contrary to our hypothesis, postdeployment social support, B = -0.59, was not associated with PTSD symptoms. These findings suggest a functional association between exposure to trauma cues and PTSD symptoms among recent-era U.S. veterans and underscore the importance of unit support during deployment.

Acupuncture Therapy for Military Veterans Suffering from Posttraumatic Stress Disorder and Related Symptoms: A Scoping Review of Clinical Studies.

Military personnel in combat face a high risk of developing posttraumatic stress disorder (PTSD). In this study, a protocol-based scoping review was conducted to identify the current status of research on the efficacy of acupuncture for treating combat-related PTSD in military personnel. A literature search was conducted across 14 databases in November 2022, and data from the included studies were collected and descriptively analyzed. A total of eight studies were included. Participants were assessed for core PTSD symptoms using the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-5 and the Clinician-Administered PTSD Scale, as well as related symptoms, such as sleep issues. Although the efficacy of acupuncture has been substantiated in numerous studies, certain metrics did not exhibit improvement. Auricular acupuncture was the most commonly used treatment (50%) followed by manual acupuncture (25%) and a combination of both (25%). Shenmen and Kidney points were frequently targeted at auricular acupoints. The treatment period varied between 5 days and 2 months. While adverse events were reported in two of the fifty-five patients in the intervention group and in four of the sixty-four patients in the control group in the randomized controlled trial studies, no fatal adverse events were reported.

A brief treatment for veterans with PTSD: an open-label case-series study.

Despite the positive outcomes observed in numerous individuals undergoing trauma-focused psychotherapy for PTSD, veterans with this condition experience notably diminished advantages from such therapeutic interventions in comparison to non-military populations. In a preliminary study we investigated the efficacy of an innovative treatment approach in a small sample of veterans (n = 7). Recognizing that accessing and targeting trauma memory in veterans with PTSD may be more challenging compared to other patient populations, we employed unique and personalized retrieval cues that engaged multiple senses and were connected to the context of their trauma. This was followed by a session focused on memory reconsolidation, which incorporated both psychological techniques (i.e., imagery rescripting) and a pharmacological component (i.e., 40 mg of propranolol). The findings from this small-scale case series cautiously indicate that this brief intervention, typically consisting of only one or two treatment sessions, shows promise in producing significant effects on symptoms of PTSD, distress and quality of life.This is particularly noteworthy given the complex symptomatology experienced by the veterans in this study. To summarize, there are grounds for optimism regarding this brief treatment of combat-related PTSD. It appears that the potential for positive outcomes is far greater than commonly believed, as demonstrated by the encouraging results of this pilot study.

Crossing the Rivers of the Tartarus: The Grief Process among Combat-Related PTSD Patients

The third stage of Pierre Janet’s model of trauma-focused treatment focuses on personality reintegration and rehabilitation and includes psychoeducation and hypnosis. According to the Jungian conceptualization presented herein, therapeutic work with combat posttraumatic stress disorder (PTSD) patients at this stage involves the completion of the grief process, during which there is a metaphoric descent to the underworld and a crossing of the rivers of the underworld, which represent complex emotional states. During the treatment of these patients, the therapist embodies, or personifies, the ancient Greek god Hermes, a psychopomp and mediator between different worlds who facilitates the healing process.

Is avoidance the only issue? A case study of "self-triggering" in combat-related posttraumatic stress disorder.

We explore the emerging concept of "self-triggering" through a case illustration of a Vietnam veteran with posttraumatic stress disorder (PTSD) who engaged in self-triggering for 50 years after his index trauma. He reduced the frequency of self-triggering upon receiving a combination of cognitive processing therapy and behavioral exposure treatment. This article provides a brief overview of the emerging literature on self-triggering, proposes theory for its function, and discusses how self-triggering affected the treatment of this veteran's chronic PTSD. Through clinical intervention that focused on what to approach (i.e., real-world experiences) and what to avoid (i.e., online triggering videos), the veteran stopped one kind of self-triggering but not another. The veteran attributed much of his positive behavior change to desire to honor the life of a young boy whose likely death he witnessed in Vietnam. Though people with PTSD often go to great lengths to avoid reminders of their trauma, there is a subset who seek reminders that trigger distressing reexperiencing symptoms. Such puzzling self-triggering behavior in those with PTSD is seldom studied and poorly understood. The details of this veteran's experience present a compelling case for self-triggering as an attempt to search for meaning in one's trauma, gain control of symptoms, and punish oneself. Implications for research and clinical practice are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

P3a amplitude to trauma-related stimuli reduced after successful trauma-focused PTSD treatment

An elevated P3a amplitude to trauma-related stimuli is strongly associated with posttraumatic stress disorder (PTSD), yet little is known about whether this response to trauma-related stimuli is affected by treatment that decreases PTSD symptoms. As an analysis of secondary outcome measures from a randomized controlled trial, we investigated the latency and amplitude changes of the P3a in responses in a three-condition oddball visual task that included trauma-related (combat scenes) and trauma-unrelated (threatening animals) distractors. Fifty-five U.S. veterans diagnosed with combat-related PTSD were randomized to receive either active or sham repetitive transcranial magnetic stimulation (rTMS). All received cognitive processing therapy, CPT+A, which requires a written account of the index trauma. They were tested before and 6 months after protocol completion. P3a amplitude and response time decreases were driven largely by the changes in the responses to the trauma-related stimuli, and this decrease correlated to the decrease in PTSD symptoms. The amplitude changes were greater in those who received rTMS + CPT than in those who received sham rTMS + CPT, suggesting that rTMS plays beneficial role in reducing arousal and threat bias, which may allow for more effective engagement in trauma-focused PTSD treatment.

The Effect of Add-on Memantine in New Onset Combat-Related Posttraumatic Stress Disorder Core Symptoms: A Pilot Study.

Objective: Studies using standard neuropsychological instrumentation have shown memory deficits in posttraumatic stress disorder (PTSD) patients. We examined the efficacy and safety of memantine in new cases of combat-related PTSD in the military by conducting a 16-week prospective double-blind randomized controlled trial. Method : Twenty-six new combat-related PTSD cases were recruited from among the military personnel based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Patients were assigned to memantine and Placebo groups. They were monitored at baseline, week eight, and week 16. Memantine was added to each patient's current medication with an initial dosage of 5 mg/day, raised by 5 mg/day every week until it reached the maintenance level of 20 mg/day. The concurrent drugs were essentially kept unchanged during the trial. The primary outcome was PTSD severity as assessed by the Clinician-administered PTSD Scale (CAPS). The CAPS is a valid and reliable tool for the diagnosis of PTSD and measurement of its severity according to the DSM-4. Results: CAPS mean score in baseline (P = 0.811) and weeks eight (P = 0.389) and 16 (P = 0.066) did not show any significant differences between the two groups. The mean CAPS score in the memantine group significantly (P = 0.006) decreased (Mean differences = -8.79) compared to the placebo group, showing that intervention with memantine was effective. The mean total CAPS in weeks eight (Mean differences = -14.21) and 16 (Mean differences = -27) were less than the baseline, which was significantly meaningful (P < 0.001). Conclusion: Findings of this study suggest that add-on memantine can be effective in veteran patients with PTSD. So our data provide useful insight into the management of new cases of combat-related PTSD.

DNA methylation GrimAge acceleration in US military veterans with PTSD.

Epigenetic alterations in DNA methylation might mediate gene expression effects of trauma underlying PTSD symptoms, or effects of PTSD on related health problems. PTSD is associated with all-cause morbidity and premature mortality, suggesting accelerated biological aging. We measured genome-wide DNA methylation (Illumina MethylationEPIC BeadChip) in whole blood in a treatment study for combat-related PTSD - "PROGrESS", a multisite RCT comparing sertraline plus enhanced medication management (SERT + EMM), prolonged exposure (PE) therapy plus placebo (PE + PLB), and the combination (SERT + PE). DNA methylation was measured in 140 US military veterans who served in Iraq and/or Afghanistan (112 current PTSD cases enrolled in a PTSD treatment study and 28 veterans without PTSD history controls), and also 59 non-trauma exposed controls at baseline posttreatment (24 weeks after baseline). Increased DNA methylation GrimAge acceleration (p = 8.8e-09) was observed in patients with PTSD compared to a pooled control group (trauma exposed and non-trauma exposed), suggesting a higher risk of premature mortality in those with PTSD. There was no difference in GrimAge acceleration between combat trauma and non-trauma exposed controls. No treatment-related changes in GrimAge acceleration were found in within-subject comparisons of PTSD patients pre- to post-treatment.

Massed vs Intensive Outpatient Prolonged Exposure for Combat-Related Posttraumatic Stress Disorder

Improved, efficient, and acceptable treatments are needed for combat-related posttraumatic stress disorder (PTSD). To determine the efficacy of 2 compressed prolonged exposure (PE) therapy outpatient treatments for combat-related PTSD. This randomized clinical trial was conducted among military personnel and veterans at 4 sites in Texas from 2017 to 2019. Assessors were blinded to conditions. Data were analyzed from November 2020 to October 2022. The interventions were massed-PE, which included 15 therapy sessions of 90 minutes each over 3 weeks, vs intensive outpatient program PE (IOP-PE), which included 15 full-day therapy sessions over 3 weeks with 8 treatment augmentations. The IOP-PE intervention was hypothesized to be superior to massed-PE. Coprimary outcomes included the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) (CAPS-5) and the PTSD Checklist for DSM-5 (PCL-5) administered at baseline and posttreatment follow-ups. Measures ranged from 0 to 80, with higher scores indicating greater severity. Diagnostic remission and reliable change were secondary outcomes. Among 319 military personnel and veterans screened, 234 were randomized (mean [SD] age, 39.20 [7.72] years; 182 [78%] male participants), with 117 participants randomized to IOP-PE and 117 participants randomized to massed-PE. A total of 61 participants (26%) were African American, 58 participants (25%) were Hispanic, and 102 participants (44%) were White; 151 participants (65%) were married. Linear mixed-effects models found that CAPS-5 scores decreased in both treatment groups at the 1-month follow-up (IOP-PE: mean difference, -13.85 [95% CI, -16.47 to -11.23]; P < .001; massed-PE: mean difference, -14.13 [95% CI, -16.63 to -11.62]; P < .001). CAPS-5 change scores differed from 1- to 6-month follow-ups (mean difference, 4.44 [95% CI, 0.89 to 8.01]; P = .02). PTSD symptoms increased in massed-PE participants during follow-up (mean difference, 3.21 [95% CI, 0.65 to 5.77]; P = .01), whereas IOP-PE participants maintained treatment gains (mean difference, 1.23 [95% CI, -3.72 to 1.27]; P = .33). PCL-5 scores decreased in both groups from baseline to 1-month follow-up (IOP-PE: mean difference, -21.81 [95% CI, -25.57 to -18.04]; P < .001; massed-PE: mean difference, -19.96 [95% CI, -23.56 to -16.35]; P < .001) and were maintained at 6 months (IOP-PE: mean change, -0.21 [95% CI, -3.47 to 3.06]; P = .90; massed-PE: mean change, 3.02 [95% CI, -0.36 to 6.40]; P = .08). Both groups had notable PTSD diagnostic remission at posttreatment (IOP-PE: 48% [95% CI, 36% to 61%] of participants; massed-PE: 62% [95% CI, 51% to 73%] of participants), which was maintained at 6 months (IOP-PE: 53% [95% CI, 40% to 66%] of participants; massed-PE: 52% [95% CI, 38% to 66%] of participants). Most participants demonstrated reliable change on the CAPS-5 (61% [95% CI, 52% to 69%] of participants) and the PCL-5 (74% [95% CI, 66% to 81%] of participants) at the 1-month follow-up. These findings suggest that PE can be adapted into compressed treatment formats that effectively reduce PTSD symptoms. ClinicalTrials.gov Identifier: NCT03529435.