Background: Prolonged exposure (PE) is an effective treatment for post-traumatic stress disorder (PTSD).Objective: This study aimed to analyse the cost-effectiveness of three exposure-based... Show moreBackground: Prolonged exposure (PE) is an effective treatment for post-traumatic stress disorder (PTSD).Objective: This study aimed to analyse the cost-effectiveness of three exposure-based treatments in patients with childhood abuse-related PTSD.Method: A net–benefit analysis was conducted alongside a pragmatic randomized controlled trial with participants (N = 149) randomized to three conditions: PE (n = 48), intensified PE (i-PE, n = 51), and phase-based PE [Skills Training in Affective and Interpersonal Regulation (STAIR) + PE, n = 50]. Assessments took place at baseline (T0), post-treatment (T3), 6 month follow-up (T4), and 12 month follow-up (T5). Costs stemming from healthcare utilization and productivity losses were estimated using the Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness. Quality-adjusted life-years (QALYs) were based on the 5-level EuroQoL 5 Dimensions (EQ-5D-5L) using the Dutch tariff. Missing values of costs and utilities were multiply imputed. To compare i-PE to PE and STAIR + PE to PE, pair-wise unequal-variance t-tests were conducted. Net–benefit analysis was used to relate costs to QALYs and to draw acceptability curves.Results: Intervention costs did not differ across the three treatment conditions. Total medical costs, productivity losses, total societal costs, and EQ-5D-5L-based QALYs did not differ between treatment conditions either (all p > .10). At the relevant €50,000/QALY threshold, the probability of one treatment being more cost-effective than another was 32%, 28%, and 40% for PE, i-PE, and STAIR-PE, respectively.Conclusion: Three equally effective treatments were compared and no differences in cost-effectiveness between treatments were found. Therefore, we advocate the implementation and adoption of any of the treatments and endorse shared decision making. Show less
Hoekstra, M.; Veelen, N. van; Leeuwen, J. van; Nijdam, M.J.; Vermetten, E. 2023
Background: As Posttraumatic stress disorder (PTSD) in adolescents significantly impacts their well-being, effective treatment is of great importance. Little is known, however, about the novel,... Show moreBackground: As Posttraumatic stress disorder (PTSD) in adolescents significantly impacts their well-being, effective treatment is of great importance. Little is known, however, about the novel, multi-modal virtual reality supported, exposure-based psychotherapeutic interventions such as 3MDR in this population.Objective: To describe the 3MDR treatment of an adolescent with PTSD who did not respond to previous exposure-based PTSD interventions.Method: A 14-year-old girl diagnosed with PTSD received six sessions of 3MDR embedded in family therapy.Result: The patient tolerated the 3MDR intervention very well. Personalized music and self-selected pictures appeared to be a good fit, contributing to enhanced engagement in and adherence to the therapy. She no longer met criteria for PTSD post-intervention, and at 18 months follow-up.Conclusion: This case report suggests that 3MDR has potential as a trauma treatment for adolescents with treatment-resistant PTSD. Show less
Does, F.H.S. van der; Nagamine, M.; Wee, N.J.A. van der; Chiba, T.; Edo, N.; Kitano, M.; ... ; Giltay, E.J. 2023
Background: After the Great East Japan Earthquake [GEJE], approximately 70,000 Japan Ground Self Defense Force [JGSDF] personnel were deployed, risking Post-Traumatic Stress Disorder [PTSD]. The... Show moreBackground: After the Great East Japan Earthquake [GEJE], approximately 70,000 Japan Ground Self Defense Force [JGSDF] personnel were deployed, risking Post-Traumatic Stress Disorder [PTSD]. The network approach to psychopathology suggests that symptoms may cause and exacerbate each other, resulting in the emergence and maintenance of disorders, including PTSD. It is therefore important to further explore the temporal interplay between symptoms. Most studies assessing the factor structure of the Impact of Event Scale-Revised [IES-R] have used cross-sectional designs. In this study, the structure of the IES-R was re-evaluated while incorporating the temporal interplay between symptoms.Methods: Using Dynamic Time Warping [DTW] the distances between PTSD symptoms on the IES-R were modelled in 1120 JGSDF personnel. Highly correlated symptoms were clustered at the group level using Distatis three-way principal component analyses of the distance matrices. The resulting clusters were compared to the original three subscales of the IES-R using a Confirmatory Factor Analysis (CFA).Results: The DTW analysis yielded four symptom clusters: Intrusion (five items), Hyperarousal (six items), Avoidance (six items), and Dissociation (five items). CFA yielded better fit estimates for this four-factor solution (RMSEA = 0.084, CFI = 0.918, TLI = 0.906), compared to the original three subscales of the IES-R (RMSEA = 0.103, CFI = 0.873, TLI = 0.858).Conclusions: DTW offers a new method of modelling the temporal relationships between symptoms. It yielded four IES-R symptom clusters, which may facilitate understanding of PTSD as a complex dynamic system. Show less
Goeree, N.; Dekker, N.L.; Reuver, Y. de; Haagen, J.F.G.; Vermetten, E. 2023
While spouses of military veterans have not been directly exposed to threats during deployment, they often experience a substantial post-deployment-related health burden while living with and... Show moreWhile spouses of military veterans have not been directly exposed to threats during deployment, they often experience a substantial post-deployment-related health burden while living with and caring for a partner with deployment-related mental health issues. Drawing from in-depth interviews, this study examined how female spouses of military veterans deal with the psychosocial effects of deployment. We show how these women cope. They keep their family lives going by maintaining hope for the future. We argue that hope is a dynamic practice between reality and possibility, and different forms of hope co-exist. These range from temporary formulations of present-centered hope, and permanent hopes directed towards the future. We illustrate how spouses challenge discourses around curative futures and adjust their hopes to maintain a more satisfactory everyday life and a positive horizon towards the future. Show less
Isaksson, J.; Isaksson, M.; Stickley, A.; Vermeiren, R.; Koposov, R.; Schwab-Stone, M.; Ruchkin, V. 2023
Community violence exposure (CVE) is one of the most common adverse childhood experiences worldwide. Despite this, its potential effect on disordered eating in adolescents from different cultures... Show moreCommunity violence exposure (CVE) is one of the most common adverse childhood experiences worldwide. Despite this, its potential effect on disordered eating in adolescents from different cultures is underexplored. In the present cross-sectional study, self-reported data were collected from 9751 students (Mean age = 14.27) from Belgium, Russia and the US on CVE (witnessing violence and violence victimization), eating disorder (ED) symptoms (ED thoughts with associated compensatory behaviors), and comorbid symptoms of posttraumatic stress, depression and anxiety. Increased CVE (from no exposure to witnessing to victimization) was associated with more ED symptoms, and the associations remained significant after adjusting for comorbid conditions. The associations were similar for adolescents across the three countries. No gender differences were observed in the association between CVE and ED symptoms, even though girls in general reported more ED symptoms than boys. We conclude that CVE appears to be associated with ED symptoms in three culturally different samples of adolescents. Show less
Isaksson, J.; Isaksson, M.; Stickley, A.; Vermeiren, R.; Koposov, R.; Schwab-Stone, M.; Ruchkin, V. 2023
Community violence exposure (CVE) is one of the most common adverse childhood experiences worldwide. Despite this, its potential effect on disordered eating in adolescents from different cultures... Show moreCommunity violence exposure (CVE) is one of the most common adverse childhood experiences worldwide. Despite this, its potential effect on disordered eating in adolescents from different cultures is underexplored. In the present cross-sectional study, self-reported data were collected from 9751 students (Mean age = 14.27) from Belgium, Russia and the US on CVE (witnessing violence and violence victimization), eating disorder (ED) symptoms (ED thoughts with associated compensatory behaviors), and comorbid symptoms of posttraumatic stress, depression and anxiety. Increased CVE (from no exposure to witnessing to victimization) was associated with more ED symptoms, and the associations remained significant after adjusting for comorbid conditions. The associations were similar for adolescents across the three countries. No gender differences were observed in the association between CVE and ED symptoms, even though girls in general reported more ED symptoms than boys. We conclude that CVE appears to be associated with ED symptoms in three culturally different samples of adolescents. Show less
Post-traumatic stress disorder (PTSD) is a prevalent psychiatric condition that significantly impacts daily functioning in patients but lacks adequate treatment options. 3,4... Show morePost-traumatic stress disorder (PTSD) is a prevalent psychiatric condition that significantly impacts daily functioning in patients but lacks adequate treatment options. 3,4-methylenedioxymethamphetamine (MDMA) as an adjunct to psychotherapy for the treatment of PTSD has been studied increasingly for the last two decades and has shown promising results through quantitative data. However, few qualitative studies have been conducted to investigate patients’ experiences who participate in these trials. This study intends to complement and clarify the quantitative findings resulting from a Phase-II clinical trial for assessing the safety and efficacy of MDMA-assisted psychotherapy for PTSD by using a qualitative approach based on available material of 4 recorded and transcripted integrative sessions per participant. An Interpretative Phenomenological Analysis (IPA) was conducted for 7 participants who met criteria for severe PTSD to develop a deeper understanding of the treatment and its efficacy. Analysis results provided real-life statements from participants that reflect perceived mechanisms of change and showed to what extent their proposed working mechanisms integrate into daily life. Show less
Introduction: Military members and Veterans are at risk of developing combat-related, treatment-resistant posttraumatic stress disorder (TR-PTSD) and moral injury (MI). Conventional trauma-focused... Show moreIntroduction: Military members and Veterans are at risk of developing combat-related, treatment-resistant posttraumatic stress disorder (TR-PTSD) and moral injury (MI). Conventional trauma-focused therapies (TFTs) have shown limited success. Novel interventions including Multi-modal Motion-assisted Memory Desensitization and Reconsolidation therapy (3MDR) may prove successful in treating TR-PTSD.Objective: To qualitatively study the experiences of Canadian military members and Veterans with TR-PTSD who received the 3MDR intervention.Methods: This study explored qualitative data from a larger mixed-method waitlist control trial testing the efficacy of 3MDR in military members and veterans. Qualitative data were recorded and collected from 3MDR sessions, session debriefings and follow-up interviews up to 6 months post-intervention; the data were then thematically analyzed.Results: Three themes emerged from the data: (1) the participants' experiences with 3MDR; (2) perceived outcomes of 3MDR; and (3) keys to successful 3MDR treatment. Participants expressed that 3MDR provided an immersive environment, active engagement and empowerment. The role of the therapist as a coach and "fireteam partner" supports the participants' control over their therapy. The multi-modal nature of 3MDR, combining treadmill-walking toward self-selected trauma imagery with components of multiple conventional TFTs, was key to helping participants engage with and attribute new meaning to the memory of the traumatic experience.Discussion: Preliminary thematic analysis of participant experiences of 3MDR indicate that 3MDR has potential as an effective intervention for combat-related TR-PTSD, with significant functional, well-being and relational improvements reported post-intervention.Conclusion: Military members and Veterans are at risk of developing TR-PTSD, with worse outcomes than in civilians. Further research is needed into 3MDR and its use with other trauma-affected populations. Show less
Eshuis, L.V.; Gelderen, M.J. van; Zuiden, M. van; Nijdam, M.J.; Vermetten, E.; Olff, M.; Bakker, A. 2021
Background: Virtual reality exposure therapy (VRET) and augmented reality exposure therapy (ARET) are digitally assisted psychotherapies that potentially enhance posttraumatic stress disorder (PTSD... Show moreBackground: Virtual reality exposure therapy (VRET) and augmented reality exposure therapy (ARET) are digitally assisted psychotherapies that potentially enhance posttraumatic stress disorder (PTSD) treatment by increasing a patient's sense of presence during exposure therapy. This study aimed to systematically review current evidence regarding the efficacy of VRET and ARET as PTSD treatment. Methods: A systematic electronic database search, a systematic quality assessment and two meta-analyses were conducted in accordance with PRISMA guidelines. Results: Eleven studies on the efficacy of VRET for PTSD (n = 438) were found, but no studies on the efficacy of ARET. The majority of VRET studies were of a low quality and had heterogeneous results. Meta-analyses showed VRET outperformed waitlist control (standardized mean difference -0.64 (95% CI -1.05 to -0.22)) while no significant difference was found between VRET and active treatment conditions (standardized mean difference -0.25 (95% CI -0.77 to 0.27)). Conclusion: VRET was superior to waitlist control groups and as effective as other psychotherapies. However, the results showed considerable heterogeneity due to the low number of studies and variety of VRET methods. VRET may be an effective alternative to current treatments and shows promise for the treatment of PTSD patients that have not responded to previous treatment. Future research should focus on high quality RCTs, including information on side effects and adverse events, with sufficient numbers of participants. This study recognizes a research gap regarding the efficacy of ARET, while it may have potential for PTSD treatment. Show less
Emotionally arousing experiences are retained very well as seen in posttraumatic stress disorder (PTSD). Various lines of evidence indicate that reactivation of these memories renders them labile... Show moreEmotionally arousing experiences are retained very well as seen in posttraumatic stress disorder (PTSD). Various lines of evidence indicate that reactivation of these memories renders them labile which offers a potential time-window for intervention. We tested in non-human primates whether ketamine, administered during fear memory reactivation, affected passive (inhibitory) avoidance learning. For the consolidation of contextual emotional memory, the unescapable foot-shock paradigm in a passive avoidance task with two compartments (dark vs illuminated) was used. After entering the dark compartment, marmoset monkeys received four random foot-shocks (1 mA, 4 s) within 15-min. This stressful exposure increased the saliva cortisol and heart rate and impaired REM-sleep ( p < 0.05). One week later the monkeys were re-exposed to the stressful situation for the reconsolidation of the fearful experience. During the re-exposure the monkeys were treated with ketamine (0.5 mg/kg) or saline. In week 3, the monkeys were placed in the experimental setting to test their memory for the fearful experience. In contrast to the vehicle-treated monkeys, who avoided the dark compartment, the ketamine-treated monkeys entered the dark compartment that was previously associated with the fearful experience ( p < 0.05). Post-mortem analysis of the hippocampus showed that ketamine-treated animals exhibited less doublecortin positive neurons and BrdU-labeled cells in the dentate gyrus. This study reveals that a single low dose of ketamine, administered upon fear retrieval in monkeys, reduce contextual fear memory and attenuate neurogenesis in the hippocampus. These are important findings for considering ketamine as a potential candidate to target traumatic memories in PTSD. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ) Show less
Populations in war-torn regions are exposed to a wide array of traumatic events that can cause an enormous psychological burden. Individual characteristics influence the likelihood of being exposed... Show morePopulations in war-torn regions are exposed to a wide array of traumatic events that can cause an enormous psychological burden. Individual characteristics influence the likelihood of being exposed to certain events, pointing to systematic interindividual differences in trauma exposure. However, there is a dearth of studies examining potential patterns of trauma exposure in war regions. In this cross-sectional epidemiological study, we applied a person-centered approach to identify patterns in the exposure to conflict-related traumatic events and determine their impact on commonly reported mental health problems in a population-based sample (N = 1000) from the eastern Democratic Republic of Congo. We implemented multi-stage random cluster sampling to randomly select adults from 100 villages. Of 1000 adults (Mage = 43.19 years) included in the study, 50% were female. Results showed high prevalence of PTSD (17.0%), depression (27.8%), anxiety (25.4%) and suicidality (15.1%) following exposure to conflict-related traumatic events since 2002. Latent Class Analysis identified three distinct classes of trauma exposure: Class 1 “low-trauma-exposure” (51.4%, n = 514) was characterized by the lowest probabilities of trauma exposure. Class 2 “non-physical-trauma” (39.1%, n = 391) consisted of individuals with a high probability for exposure to non-physical trauma types only. Class 3 “interpersonal-trauma” (9.5%, n = 95) had the overall highest probability of exposure to traumatic events and was the only class affected by interpersonal-trauma types. Class membership was related to gender, age and place of living. Vulnerability to mental health problems increased from low-trauma-exposure to non-physical-trauma to interpersonal-trauma class. Our findings indicate that the exposure to traumatic events in conflict-affected populations underlies distinct patterns, with interpersonal trauma as a distinguishing marker. Vulnerability to psychopathology varies with trauma patterns, revealing patterns that include both non-physical and interpersonal traumata as most detrimental for mental health. Identification of underlying trauma patterns and their effects may improve mental health care in war-affected populations. Show less
Blase, K.; Vermetten, E.; Lehrer, P.; Gevirtz, R. 2021
Background: Heart Rate Variability Biofeedback (HRVB) is a treatment in which patients learn self-regulation of a physiological dysregulated vagal nerve function. While the therapeutic approach of... Show moreBackground: Heart Rate Variability Biofeedback (HRVB) is a treatment in which patients learn self-regulation of a physiological dysregulated vagal nerve function. While the therapeutic approach of HRVB is promising for a variety of disorders, it has not yet been regularly offered in a mental health treatment setting. Aim: To provide a systematic review about the efficacy of HRV-Biofeedback in treatment of anxiety, depression, and stress related disorders. Method: Systematic review in PubMed and Web of Science in 2020 with terms HRV, biofeedback, Post-Traumatic Stress Disorder (PTSD), depression, panic disorder, and anxiety disorder. Selection, critical appraisal, and description of the Random Controlled Trials (RCT) studies. Combined with recent meta-analyses. Results: The search resulted in a total of 881 studies. After critical appraisal, nine RCTs have been selected as well as two other relevant studies. The RCTs with control groups treatment as usual, muscle relaxation training and a "placebo"-biofeedback instrument revealed significant clinical efficacy and better results compared with control conditions, mostly significant. In the depression studies average reduction at the Beck Depression Inventory (BDI) scale was 64% (HRVB plus Treatment as Usual (TAU) versus 25% (control group with TAU) and 30% reduction (HRVB) at the PSQ scale versus 7% (control group with TAU). In the PTSD studies average reduction at the BDI-scale was 53% (HRV plus TAU) versus 24% (control group with TAU) and 22% (HRVB) versus 10% (TAU) with the PTSD Checklist (PCL). In other systematic reviews significant effects have been shown for HRV-Biofeedback in treatment of asthma, coronary artery disease, sleeping disorders, postpartum depression and stress and anxiety. Conclusion: This systematic review shows significant improvement of the non-invasive HRVB training in stress related disorders like PTSD, depression, and panic disorder, in particular when combined with cognitive behavioral therapy or different TAU. Effects were visible after four weeks of training, but clinical practice in a longer daily self-treatment of eight weeks is more promising. More research to integrate HRVB in treatment of stress related disorders in psychiatry is warranted, as well as research focused on the neurophysiological mechanisms. Show less
Houtert, E.A.E. van; Endenburg, N.; Rodenburg, T.B.; Vermetten, E. 2021
Simple SummaryA growing number of people are supported by specialized service dogs. These dogs are highly trained to improve human welfare, yet not much is known about their own welfare. One of the... Show moreSimple SummaryA growing number of people are supported by specialized service dogs. These dogs are highly trained to improve human welfare, yet not much is known about their own welfare. One of the ways in which welfare can be measured is through the expression of stress via the hormone cortisol. In this study, we investigated the level of cortisol in saliva, a measure for physiological stress, in 19 service dogs. We measured cortisol in the dogs' saliva 15 min after arrival at a training ground, before partaking in a training session for service dogs, after participation in the training session, and after a 45-min free play period. We found no elevated levels of cortisol after the training session. Instead, we found that cortisol had lowered when compared to before the training. Additionally, we found that cortisol was highest 15 min after arriving at the training round and after 45 min of free play. This led to the conclusion that dogs in our study did not seem to have a stress response in response to participation in the training.Only a few studies have investigated the welfare of animals participating in animal-assisted interventions (AAIs). Most of these studies focus on dogs in therapeutic settings. There are, however, also dogs-service dogs-that are employed to continuously support a single human. Because the welfare of these service dogs is important for the sustainability of their role, the aim of this study was to investigate their stress response to service dog training sessions. To do this, we took repeated salivary cortisol samples from dogs who participated in a training session (n = 19). Samples were taken just after arrival at the training ground, before training, after training, and after a period of free play. Our results showed that mean cortisol levels in all samples were relatively low (between 1.55 +/- 1.10 and 2.73 +/- 1.47 nmol/L) compared to similar studies. Analysis further showed that samples taken before and after participation in the training's session did not differ from one another. Mean cortisol levels in both situations were additionally lower than those upon arrival at the training site and after a period of free play. This led to the conclusion that the dogs in our study did not seem to experience training as stressful. Show less
Posttraumatic stress disorder (PTSD) is an often chronic condition for which currently available medications have limited efficacy. Medical cannabis is increasingly used to treat patients with PTSD... Show morePosttraumatic stress disorder (PTSD) is an often chronic condition for which currently available medications have limited efficacy. Medical cannabis is increasingly used to treat patients with PTSD; however, evidence for the efficacy and safety of cannabinoids is scarce. To learn more about patients' opinions on and experiences with medical cannabis, we organized a focus group discussion among military veterans (N = 7) with chronic PTSD who were treated with medical cannabis. Afterwards, some of their partners (N = 4) joined the group for an evaluation, during which they shared their perspective on their partner's use of medical cannabis. Both sessions were audio-recorded, transcribed verbatim, and analyzed by means of qualitative content analysis. Five overarching themes were identified. The first four themes related to the different phases of medical cannabis use - namely, 1) Consideration; 2) Initiation; 3) Usage; and 4) Discontinuation. The fifth theme related to several general aspects of medical cannabis use. Patients used medical cannabis to manage their symptoms and did not experience an urge to "get high." They used a variety of different cannabis strains and dosages and reported several therapeutic effects, including an increased quality of sleep. Furthermore, discussions about the experienced stigma surrounding cannabis generated insights with implications for the initiation of medical cannabis use. These results underscore the value of qualitative research in this field and are relevant for the design of future clinical trials on the use of medical cannabis for the treatment of PTSD. (c) 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/) Show less
Bisson, J.I.; Deursen, R. van; Hannigan, B.; Kitchiner, N.; Barawi, K.; Jones, K.; ... ; Vermetten, E. 2020
Objective To explore the potential efficacy of multi-modular motion-assisted memory desensitization and reprocessing (3MDR) in British military veterans with treatment-resistant service-related... Show moreObjective To explore the potential efficacy of multi-modular motion-assisted memory desensitization and reprocessing (3MDR) in British military veterans with treatment-resistant service-related PTSD. Methods Exploratory single-blind, randomized, parallel arm, cross-over controlled trial with nested process evaluation to assess fidelity, adherence and factors that influence outcome. Results A total of 42 participants (all male) were randomized with 83% retention at 12 weeks and 86% at 26 weeks. The difference in mean Clinician-Administered PTSD Scale for DSM-5 scores between the immediate and delayed 3MDR arms was -9.38 (95% CI -17.33 to -1.44,P = 0.021) at 12 weeks and -3.59 (-14.39 to 7.20,P = 0.513) at 26 weeks when both groups had received 3MDR. The likely effect size of 3MDR was found to be 0.65. Improvements were maintained at 26-week follow-up. 3MDR was found to be acceptable to most, but not all, participants. Several factors that may impact efficacy and acceptability of 3MDR were identified. Conclusion 3MDR is a promising new intervention for treatment-resistant PTSD with emerging evidence of effect. Show less
Krediet, E.; Bostoen, T.; Breeksema, J.; Schagen, A. van; Passie, T.; Vermetten, E. 2020
There are few medications with demonstrated efficacy for the treatment of posttraumatic stress disorder (PTSD). Treatment guidelines have unequivocally designated psychotherapy as a first line... Show moreThere are few medications with demonstrated efficacy for the treatment of posttraumatic stress disorder (PTSD). Treatment guidelines have unequivocally designated psychotherapy as a first line treatment for PTSD. Yet, even after psychotherapy, PTSD often remains a chronic illness, with high rates of psychiatric and medical comorbidity. Meanwhile, the search for and development of drugs with new mechanisms of action has stalled. Therefore, there is an urgent need to explore not just novel compounds but novel approaches for the treatment of PTSD. A promising new approach involves the use of psychedelic drugs. Within the past few years, 2 psychedelics have received breakthrough designations for psychiatric indications from the US Food and Drug Administration, and several psychedelics are currently being investigated for the treatment of PTSD. This review discusses 4 types of compounds: 3,4-methylenedioxymethamphetamine, ketamine, classical psychedelics (e.g., psilocybin and lysergic acid diethylamide), and cannabinoids. We describe the therapeutic rationale, the setting in which they are being administered, and their current state of evidence in the treatment of PTSD. Each compound provides unique qualities for the treatment of PTSD, from their use to rapidly target symptoms to their use as adjuncts to facilitate psychotherapeutic treatments. Several questions are formulated that outline an agenda for future research. Show less
Background Epigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450... Show moreBackground Epigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450 BeadChip) collected prior to and following combat exposure in three cohorts of male military members were analyzed to assess whether DNA methylation profiles are associated with the development of PTSD. A total of 123 PTSD cases and 143 trauma-exposed controls were included in the analyses. The Psychiatric Genomics Consortium (PGC) PTSD EWAS QC pipeline was used on all cohorts, and results were combined using a sample size weighted meta-analysis in a two-stage design. In stage one, we jointly analyzed data of two new cohorts (N = 126 and 78) for gene discovery, and sought to replicate significant findings in a third, previously published cohort (N = 62) to assess the robustness of our results. In stage 2, we aimed at maximizing power for gene discovery by combining all three cohorts in a meta-analysis. Results Stage 1 analyses identified four CpG sites in which, conditional on pre-deployment DNA methylation, post-deployment DNA methylation was significantly associated with PTSD status after epigenome-wide adjustment for multiple comparisons. The most significant (intergenic) CpG cg05656210 (p = 1.0 x 10(-08)) was located on 5q31 and significantly replicated in the third cohort. In addition, 19 differentially methylated regions (DMRs) were identified, but failed replication. Stage 2 analyses identified three epigenome-wide significant CpGs, the intergenic CpG cg05656210 and two additional CpGs located in MAD1L1 (cg12169700) and HEXDC (cg20756026). Interestingly, cg12169700 had an underlying single nucleotide polymorphism (SNP) which was located within the same LD block as a recently identified PTSD-associated SNP in MAD1L1. Stage 2 analyses further identified 12 significant differential methylated regions (DMRs), 1 of which was located in MAD1L1 and 4 were situated in the human leukocyte antigen (HLA) region. Conclusions This study suggests that the development of combat-related PTSD is associated with distinct methylation patterns in several genomic positions and regions. Our most prominent findings suggest the involvement of the immune system through the HLA region and HEXDC, and MAD1L1 which was previously associated with PTSD. Show less
Gelderen, M.J. van; Nijdam, M.J.; Dubbink, G.E.; Sleijpen, M.; Vermetten, E. 2020
Background: A novel intervention, Multi-modular motion-assisted memory desensitization and reconsolidation (3MDR), aims to reduce avoidance and improve engagement for patients with posttraumatic... Show moreBackground: A novel intervention, Multi-modular motion-assisted memory desensitization and reconsolidation (3MDR), aims to reduce avoidance and improve engagement for patients with posttraumatic stress disorder (PTSD) who did not sufficiently respond to previous treatments. It has been found to effectively reduce PTSD symptoms for veterans with treatment-resistant PTSD. Symptomatic measures alone might not capture all treatment effects, and addition of qualitative outcomes may provide deeper understanding of treatment processes and treatment-induced changes.Objective: To study the perspectives of veterans with treatment-resistant PTSD on 3MDR treatment processes and effects and explore the relation of their experiences to PTSD symptom improvement.Method: A convergent parallel mixed methods design was applied. For the qualitative part, open-ended question interviews were conducted until data saturation was reached (N = 10). Thematic analysis, rooted in grounded theory, was performed. Quantitative data included pre- to posttreatment responder status based on a structured clinical interview for PTSD.Results: Treatment processes endorsed by the veterans were engaging, regulating distress, feeling supported, facing traumatic memories, allowing emotions, associating, and disengaging from trauma. In terms of effects, veterans reported positive changes following 3MDR, including openness, new learning, self-understanding, closure, and reintegration. High comparability across themes was observed for responders and non-responders, except for the themes closure and reintegration, which were reported more often or more in depth by responders.Conclusions: Veterans indicated 3MDR treatment processes that complied with its aims of breaking through avoidance and increasing engagement, thereby facilitating traumatic memory retrieval and processing. However, this did not necessarily translate into PTSD symptom improvement for all veterans. Walking towards trauma-related pictures was highlighted as unique component of 3MDR and connected to specific treatment processes and effects. Positive changes following 3MDR were experienced outside the domain of PTSD symptom improvement, implicating that 3MDR may beneficially impact veterans beyond symptom changes alone. Show less
Background: Stressors activate a wide spectrum of interacting hormonal and neuronal systems resulting in behavioral and physiological responses, with consequences for the development of... Show moreBackground: Stressors activate a wide spectrum of interacting hormonal and neuronal systems resulting in behavioral and physiological responses, with consequences for the development of psychopathology. Several recent studies demonstrated that treatment with the glucocorticoid receptor (GR) antagonist RU486 during adulthood normalized effects of early life stress. We aimed to evaluate the potential of RU486 to reverse stress-induced changes in an animal model of adult stress.Method: We employed the single-prolonged stress (SPS) model as a multimodal stress exposure protocol in male rats. SPS rats and unstressed controls were treated with RU486 on days 8, 9, 10 after stress exposure and the effects of treatment were evaluated after another 4 days. We determined body weight gain, corticosterone levels, behavioral reactivity in anxiety tests, and brain gene expression of c-fos, corticosteroid receptors, drivers of the stress response and genes (epi-)genitally linked to PTSD.Results: RU486 affected body weight gain, corticosterone levels and open field behavior only in SPS rats. RU486 had history-independent effects in reducing fear in the elevated plus maze and fear conditioning behavior. Gene expression analysis showed a diversity of in- and interdependent effects of stress and RU486.Conclusion: The effects of RU486 applied 1 week after stress and measured 4 days after treatment demonstrate that in the state of post-SPS the GR-dependence of homeostatic processes has changed. This suggests that GR-mediated processes are part of allostatic regulation after adult stress. The normalization of a number of SPS-effects after RU486 treatment reinforces the potential of targeting GR for treatment of stress-related psychopathologies. Show less
