Agnes van Minnen

Background: Evidence indicates the potential efficacy of trauma-focused therapies for post-traumatic stress disorder (PTSD) in psychosis. This is the first randomized controlled trial to evaluate the superiority of Prolonged Exposure (PE), Eye Movement Desensitization and Reprocessing therapy (EMDR), and Cognitive Restructuring (CR) plus treatment as usual, compared to a waiting-list (WL) plus treatment as usual control group. Methods: We conducted a multicenter, assessor-masked, randomized controlled trial in patients with a lifetime schizophrenia spectrum psychotic disorder and PTSD. Participants ( N = 162) were randomized (1:1:1:1) to PE, EMDR, CR, or WL and followed up until 6 months post-randomization. Therapy conditions had a maximum of 16 twice-weekly sessions. Primary outcome was researcher-rated PTSD symptom severity (Clinician-Administered PTSD Scale for DSM-5; CAPS-5). Results: PE, EMDR, and CR significantly reduced PTSD severity compared to WL over time from baseline to 6-month follow-up. At 6-months, adjusted differences and between-group effect sizes on the CAPS-5 were −9.76 (95% CI −16.13,−3.38; p = 0.0029) with d = −0.90 (95% CI −1.36,−0.44) for PE, −11.74 (95% CI −18.04,−5.44; p = 0.0003) with d = −1.04 (95% CI −1.50,−0.58) for EMDR, and −12.72 (95% CI −18.89,−6.55; p = 0.0001) with d = −1.00 (95% CI −1.46,−0.54) for CR. Significant therapy effects were also found for secondary PTSD (-related) outcomes, but not for psychosis. Conclusions: In comparison to WL, PE, EMDR, and CR were effective in reducing PTSD symptoms in individuals with PTSD and psychosis, with large effects. Replication in larger samples is needed, although these results support expanding access to trauma therapies in this underserved population.

Exposure therapy is an effective treatment for disorders characterized by fear and anxiety, but not all patients achieve symptom relief and many relapse outside of the original therapeutic context. Alterations in fear extinction – widely considered the central mechanism of exposure therapy – are observed in clinical populations, and have been linked to exposure treatment outcomes. However, extinction learning deficits alone cannot explain why fear returns when contextual conditions change. It is therefore pivotal to investigate the predictive value of contextual modulation of extinction learning for long-term exposure success. In this study, we examined whether contextual modulation of fear and safety learning in a Pavlovian fear-conditioning paradigm predicted intensive exposure treatment outcomes in patients with PTSD, OCD, and panic disorder (n = 109). We hypothesised that better contextual modulation would predict more favourable treatment outcomes across patient groups. Before treatment, participants completed fear acquisition and extinction in two different contexts, and three test phases assessing conditioned responses in the extinction and acquisition context, and a novel context. Fear responses were indexed by US expectancies and distress ratings. Symptom improvements were assessed using disorder-specific clinician-rated and self-report measures, as well as a transdiagnostic index of symptom distress. Our findings show that greater extinction context retention predicted more symptom reduction post-treatment, although effects were not consistent across outcome measures. These findings offer new insights into mechanisms that may underlie exposure success and highlight the translational value of contextual retention of extinction learning in fear-conditioning paradigms.

Background: A conversation between a victim and a perpetrator of sexual abuse has the potential to reduce posttraumatic stress disorder (PTSD) symptoms in the victim. However, an actual conversation may not always be possible or feasible. Deepfake technology may offer a way to simulate a conversation in a clinical context. Therefore, a feasible, acceptable and potentially effective intervention protocol is required.Objective: We aimed to develop an intervention protocol for a deepfake victim-perpetrator conversation to be used in the treatment of patients with sexual abuse-related PTSD, that would be technologically, legally, ethically, and clinically feasible as well as acceptable. In addition, we aimed to design a single-case experimental design (SCED) multiple baseline study to evaluate its efficacy.Method: The intervention protocol was developed through an iterative multidisciplinary process following established guidelines for complex intervention development. Based on a literature review and interviews with 15 experts and patient representatives, a draft intervention protocol was created and subsequently evaluated, piloted and refined. A consequent study protocol was then designed in accordance with the SPIRIT guidelines.Results: The development process resulted in an intervention protocol for a half-day perpetrator conversation using deepfake technology. The intervention is grounded in cognitive-behavioural therapy and emotional processing theory, and consists of a preparatory session, a deepfake session, and a debriefing session, to be conducted by two therapists. The intervention is tested in a SCED multiple baseline study of 10 patients with sexual abuse-related PTSD who are randomly assigned to a baseline period of 10, 15 or 20 days. Outcomes (changes in negative cognitions, PTSD, guilt and shame, forgiveness, and empowerment) are assessed through 20-30 daily measurements and four main assessments, and analysed using Bayesian statistics.Conclusion: A feasible and acceptable intervention protocol for a deepfake intervention was developed. Its efficacy is tested in a multiple-baseline study.

Trauma and post‐traumatic stress are involved in the aetiology and maintenance of voice‐hearing. It has been proposed that trauma‐focused therapy (TFT) might affect voice‐hearing, but previous studies are limited and remain undecided. Objectives: We aimed to investigate the effect of TFT on voice‐hearing in people with PTSD and psychosis using experience sampling method (ESM). A secondary aim was to explore how changes in voice‐hearing are related to changes in PTSD. Design: This is an adjunct longitudinal ESM study of a sub‐group of participants ( N = 39) from a randomised controlled trial that compared TFT to a waiting‐list control group. Methods: Voice‐hearing participants filled in 10 daily voice‐hearing‐related questionnaires for six consecutive days at baseline and post‐treatment at pseudo‐random times during the day. PTSD symptom severity was assessed at baseline and post‐treatment. Multilevel linear regression was used to test the effect of TFT on voice‐hearing and to analyse the relationship between changes in voice‐hearing and changes in PTSD. Results: The intention‐to‐treat analysis showed a significant interaction effect between time and treatment condition ( p < .00001) with a small effect size ( dppc2 = −0.27), indicating a larger decrease in voice‐hearing in the TFT group than in the waiting‐list control group. Also, a significant association was observed between changes in PTSD symptoms and changes in voice‐hearing ( p < .00001). Conclusions: Our findings tentatively suggest that, even when voices are not targeted directly, TFT for PTSD can alleviate distressing voices.

Despite the availability of various treatment approaches for patients with posttraumatic stress disorder (PTSD), some patients do not respond to these therapies, and novel treatment approaches are needed. This study investigated the efficacy of mifepristone, a glucocorticoid receptor antagonist, in treatment-resistant PTSD patients. Three patients with PTSD who were resistant to standard psychological and pharmacological treatments were prescribed mifepristone (6001,200mg/day) for 1 week. A baseline-controlled single-case design was used, involving a 2-week baseline phase (no intervention), a 1-week intervention phase (mifepristone), and a 2-week postintervention phase. The primary outcome measure, self-reported PTSD symptom severity (PCL-5), was assessed daily, with participants providing their own control condition. Two of the three patients experienced a significant reduction in PTSD symptom severity after the intervention phase and no longer met the diagnostic criteria for PTSD. These positive results were maintained during long-term follow-up. These findings support the potential effectiveness of mifepristone in the treatment of patients with treatment-resistant PTSD. However, our findings must be interpreted with caution, and further studies with larger sample sizes and more rigorous designs are necessary to confirm the promising results.

Recent studies indicated that Prolonged Exposure (PE) is safe and effective for posttraumatic stress disorder (PTSD). It is unclear whether PE also leads to a reduction in comorbid diagnoses. Data from a large randomized controlled trial (N = 149) on the effects of three variants of PE for PTSD were used. We examined the treatment effects on co-morbid diagnoses of depressive, anxiety, obsessive compulsive, substance abuse, psychotic, eating and personality disorders in a sample of patients with PTSD related to childhood abuse. Outcomes were assessed with clinical interviews at baseline, post-treatment and at 6- and 12-month follow-up. All variants of PE led to a decrease from baseline to post-treatment in diagnoses of depressive, anxiety, substance use and personality disorders. Improvements were sustained during follow-up. We found an additional decrease in the number of patients that fulfilled the diagnostic criteria of a depressive disorder between 6- and 12-month follow-up. No significant changes were observed for the presence of OCD, psychotic and eating disorders. Findings suggest that it is effective to treat PTSD related to childhood abuse with trauma-focused treatments since our 14-to-16 weeks PE for PTSD resulted in reductions in comorbid diagnoses of depressive, anxiety, substance use and personality disorders.

Dysfunctional cognitions play a central role in the development of post-traumatic stress disorder (PTSD). However the role of specific dissociation-related beliefs about memory has not been previously investigated. This study aimed to investigate the role of dissociation-related beliefs about memory in trauma-focused treatment. It was hypothesized that patients with the dissociative subtype of PTSD would show higher levels of dissociation-related beliefs, dissociation-related beliefs about memory would decrease after trauma-focused treatment, and higher pre-treatment dissociation-related beliefs would be associated with fewer changes in PTSD symptoms. Post-traumatic symptoms, dissociative symptoms, and dissociation-related beliefs about memory were assessed in a sample of patients diagnosed with PTSD (n = 111) or the dissociative subtype of PTSD (n = 61). They underwent intensive trauma-focused treatment consisting of four or eight consecutive treatment days. On each treatment day, patients received 90 min of individual prolonged exposure (PE) in the morning and 90 min of individual eye movement desensitization and reprocessing (EMDR) therapy in the afternoon. The relationship between dissociation-related beliefs about memory and the effects of trauma-focused treatment was investigated. Dissociation-related beliefs about memory were significantly associated with PTSD and its dissociative symptoms. In addition, consistent with our hypothesis, patients with the dissociative subtype of PTSD scored significantly higher on dissociation-related beliefs about memory pre-treatment than those without the dissociative subtype. Additionally, the severity of these beliefs decreased significantly after trauma-related treatment. Contrary to our hypothesis, elevated dissociation-related beliefs did not negatively influence treatment outcome. The results of the current study suggest that dissociation-related beliefs do not influence the outcome of trauma-focused treatment, and that trauma-focused treatment does not need to be altered specifically for patients experiencing more dissociation-related beliefs about memory because these beliefs decrease in association with treatment.

The extent to which intensive trauma-focused treatment for individuals with post-traumatic stress disorder (PTSD) is also effective in treating comorbid major depressive disorder (MDD) remains unclear. The purpose of the present study was to test the hypothesis that brief intensive trauma-focused therapy for PTSD is associated with significant reductions in depressive symptoms and loss of diagnostic status of MDD. A total of 334 adult patients with PTSD (189 patients who were also diagnosed with MDD) underwent a brief intensive trauma-focused treatment programme consisting of EMDR therapy, prolonged exposure, physical activity, and psychoeducation. At pre-treatment, post-treatment and 6-month follow-up, severity and diagnostic status of PTSD and MDD were assessed. A linear mixed model was used to analyze changes in the severity of PTSD and depressive symptoms, whereas a generalized linear mixed model was used to determine changes in the MDD diagnostic status. Treatment resulted in a significant and strong decrease of PTSD and MDD symptoms at post-treatment (d = 2.34 and 1.22, respectively), and at 6-month follow-up (d = 1.67 and 0.73, respectively). The proportion of patients fulfilling the diagnostic status of MDD changed from 57% at pre-treatment to 33% at the 6-month follow-up. Although the initial response to treatment did not differ between patients with and without comorbid MDD, for both groups a significant relapse in depressive symptoms was found after six months, which could be explained almost entirely by the presence of CPTSD at baseline. The results support the notion that brief, intensive trauma-focused treatment is highly effective for individuals with PTSD and comorbid MDD. Because patients with CPTSD are vulnerable to relapse in depressive symptoms, this target group may require additional treatment.

Concern for symptom exacerbation and treatment drop‐out is an important barrier to the implementation of trauma‐focused therapy (TFT), especially in people with a psychotic disorder. This study, which was part of a multicenter randomized controlled trial, investigated posttraumatic stress disorder (PTSD) symptom exacerbation during eye movement desensitization reprocessing (EMDR) therapy and prolonged exposure (PE) in a sample of 99 participants with PTSD and psychosis. Symptom exacerbations during the first four sessions (early exacerbation) and between‐session exacerbations over the course of therapy were monitored using the PTSD Symptom Scale–Self Report. Analyses of covariance and chi‐square tests were conducted to investigate exacerbation rates and their associations with treatment response and drop‐out. Both early exacerbation and between‐session exacerbation were relatively common (32.3% and 46.5%, respectively) but were unrelated to poor treatment response or an increased likelihood of treatment drop‐out. Both clinicians and patients need to be aware that symptom exacerbation during TFT is common and not related to poor outcomes. Symptom exacerbation can be part of the therapeutic process, should be acknowledged and guided, and should not be a barrier to the implementation of TFT in people with psychosis.