Predictors of treatment attendance in patients with posttraumatic stress disorder and comorbid personality disorders.

INTRODUCTION: High dropout and low treatment attendance rates among patients with posttraumatic stress disorder (PTSD) and personality disorders (PDs) continue to pose a significant challenge. Despite numerous studies focusing on enhancing treatment attendance, the identification of consistent and reliable predictors in patients with PTSD and comorbid PDs remains limited. OBJECTIVES: This study aims to investigate a wide range of potential predictors of treatment attendance, encompassing demographic, patient-severity, treatment, and therapist-related variables in patients with PTSD and comorbid borderline and/or cluster C PDs. METHODS: Utilizing data from 255 patients participating in two randomized controlled trials comparing trauma-focused treatment with or without concurrent PD treatment, candidate predictors were individually analyzed in univariate regression models. Significant predictors were then combined in a multiple ordinal regression model. RESULTS: In total, 40% of patients attended fewer trauma-focused treatment sessions than the minimum recommended in treatment guidelines. Out of the 38 candidate predictors examined, five significant, independent predictors of treatment attendance emerged in a multiple ordinal regression model. Higher baseline PTSD severity (OR = 1.04, p = .036), higher education level (OR = 1.22, p = .009) and a stronger patient-rated working alliance (OR = 1.72, p = .047) with the therapist predicted higher treatment attendance. Conversely, inadequate social support from friends (OR = 0.90, p = .042) and concurrent PD treatment and trauma-focused treatment (OR = 0.52, p = .022) were associated with lower treatment attendance. CONCLUSIONS: In conclusion, this constitutes the first study investigating predictors of treatment attendance in patients with PTSD and comorbid PDs. The results highlight the complexity of pinpointing reliable predictors. Nevertheless, the identification of five predictors provides valuable insights, aiding clinicians in customizing treatment strategies for individual patients and enhancing overall treatment attendance.

A randomized controlled trial comparing the clinical efficacy and cost-effectiveness of eye movement desensitization and reprocessing (EMDR) and integrated EMDR-Dialectical Behavioural Therapy (DBT) in the treatment of patients with post-traumatic stress disorder and comorbid (Sub)clinical borderline personality disorder: study design.

BACKGROUND: Comorbidity between Posttraumatic Stress Disorder (PTSD) and Borderline Personality Disorder (BPD) is high. There is growing motivation among clinicians to offer PTSD treatments - such as Eye Movement Desensitization and Reprocessing (EMDR) - to patients with PTSD and comorbid BPD. However, a large subgroup with comorbid BPD does not sufficiently respond to PTSD treatment and is more likely to be excluded or to dropout from treatment. Dialectical Behaviour Therapy (DBT) for BPD is well established and although there is some evidence that DBT combined with DBT Prolonged Exposure (DBT + DBT PE) is twice as effective in reducing PTSD symptoms than DBT alone, the comparative efficacy of integrated PTSD-DBT and PTSD-only treatment has not been investigated yet. The current study will therefore evaluate the comparative clinical efficacy and cost-effectiveness of EMDR-DBT and EMDR-only in patients with PTSD and comorbid (sub)clinical BPD. Moreover, it is not clear yet what treatment works best for which individual patient. The current study will therefore evaluate neurobiological predictors and mediators of the individual response to treatment. METHOD: A randomized controlled trial comparing the clinical efficacy and cost-effectiveness of integrated EMDR-DBT (n = 63) and EMDR-only (n = 63) in treatment-seeking adult patients with PTSD and comorbid (sub)clinical BPD. In addition, neurobiological predictors and mediators of treatment outcome, such as hair cortisol, FKBP5 and BDNF protein levels and FKBP5 and BDNF methylation status, are measured through hair and blood samples. DISCUSSION: This is the first study to compare the clinical efficacy and cost-effectiveness of integrated EMDR-DBT and EMDR-only in patients with PTSD and comorbid (sub)clinical BPD, while simultaneously identifying individual predictors and mediators of treatment response. Results will reveal which treatment works best for which individual patient, thereby guiding individual treatment choices and personalizing psychiatry. TRIAL REGISTRATION: Clinical Trials, NCT03833453 . Retrospectively registered, 15 March 2019.

Brain activation during an emotional task in participants with PTSD and borderline and/or cluster C personality disorders.

INTRODUCTION: Although comorbidity of post-traumatic stress disorder (PTSD) with borderline personality disorder (BPD) and/or cluster C personality disorders (CPD) is common, neural correlates of this comorbidity are unknown. METHODS: We acquired functional MRI scans during an emotional face task in participants with PTSD + CPD (n = 34), PTSD + BPD (n = 24), PTSD + BPD + CPD (n = 18) and controls (n = 30). We used ANCOVAs and Bayesian analyses on specific ROIs in a fearful vs. scrambled faces contrast. We also investigated associations with clinical measures. RESULTS: There were no robust differences in brain activation between the groups with ANCOVAs. Transdiagnostically, we found a negative association between severity of dissociation and right insula and right dmPFC activation, and emotion regulation problems with right dmPFC activation. Bayesian analyses showed credible evidence for higher activation in all ROIs in the PTSD + BPD + CPD group compared to PTSD + BPD and PTSD + CPD. DISCUSSION: Our Bayesian and correlation analyses support new dimensional conceptualizations of personality disorders.

Trauma-focused and personality disorder treatment for posttraumatic stress disorder and comorbid cluster C personality disorder: a randomized clinical trial.

Background: Posttraumatic stress disorder (PTSD) is associated with high rates of cluster C personality disorders (PD), which may negatively affect PTSD treatment. It is unknown whether concurrent treatment for PTSD and comorbid PD leads to superior treatment effects, compared to standard trauma-focused treatment.Objective: The objective was to test the efficacy of adding personality disorder treatment (group schema therapy; GST) to individual trauma-focused treatment (imagery rescripting; ImRs).Method: A two-arm randomized clinical trial (1:1 allocation ratio) was conducted between 2018 and 2023 at two sites of a mental health institution in the Netherlands. Raters were blind to treatment allocation. Adult outpatients with PTSD and comorbid cluster C personality disorders were randomized to receive either ImRs (12-18 sessions) or ImRs + GST (12-18 ImRs + 52-58 GST). The main outcome was PTSD severity one year after start of treatment measured with the Clinician-Administered PTSD Scale for DSM-5.Results: Of 130 patients (mean [SD] age = 40.6 [11.2], 110 [85%] females), 66 were assigned to ImRs and 64 to ImRs + GST. At 12 months, there were large decreases in PTSD severity (dImRs = 2.42, 95%CI = 1.97-2.87; dImRs + GST = 2.44, 95%CI = 1.99-2.90), but there was no significant difference between conditions (d = 0.02, 95%CI = -0.33-0.36, p = .944). Reductions in personality disorder symptoms and all other secondary outcomes were observed in both conditions. There were no significant differences between conditions on any of the secondary outcomes at 12 months.Conclusion: The more intensive concurrent trauma-focused and personality disorder treatment (ImRs + GST) was not superior to trauma-focused treatment alone (ImRs) for patients with PTSD and comorbid CPD. This suggests that trauma-focused treatment is the preferred primary treatment in patients presenting with both internalizing personality disorder and PTSD, reserving the stepping up to more intensive psychotherapy aimed at the personality disorder as a second line of treatment.Trial registration: ClinicalTrials.gov identifier: NCT03833531.

Concurrent trauma-focused and personality disorder treatment was not superior to only trauma-focused treatment for patients with posttraumatic stress disorder (PTSD) and comorbid cluster C personality disorders.Large reductions in PTSD severity and medium-to-large reductions in all secondary outcomes, including personality disorder symptoms, were observed in both treatment arms.These findings are remarkable, given the higher therapy dosage and specialized treatment for personality disorder comorbidity in the combined treatment arm.

Effects of psychotherapy on brain activation during negative emotional processing in patients with posttraumatic stress disorder: a systematic review and meta-analysis.

Post-traumatic stress disorder (PTSD) is a debilitating condition which has been related to problems in emotional regulation, memory and cognitive control. Psychotherapy has a non-response rate of around 50% and understanding the neurobiological working mechanisms might help improve treatment. To integrate findings from multiple smaller studies, we performed the first meta-analysis of changes in brain activation with a specific focus on emotional processing after psychotherapy in PTSD patients. We performed a meta-analysis of brain activation changes after treatment during emotional processing for PTSD with seed-based d mapping using a pre-registered protocol (PROSPERO CRD42020211039). We analyzed twelve studies with 191 PTSD patients after screening 3700 studies. We performed systematic quality assessment both for the therapeutic interventions and neuroimaging methods. Analyses were done in the full sample and in a subset of studies that reported whole-brain results. We found decreased activation after psychotherapy in the left amygdala, (para)hippocampus, medial temporal lobe, inferior frontal gyrus, ventrolateral prefrontal cortex, right pallidum, anterior cingulate cortex, bilateral putamen, and insula. Decreased activation in the left amygdala and left ventrolateral PFC was also found in eight studies that reported whole-brain findings. Results did not survive correction for multiple comparisons. There is tentative support for decreased activation in the fear and cognitive control networks during emotional processing after psychotherapy for PTSD. Future studies would benefit from adopting a larger sample size, using designs that control for confounding variables, and investigating heterogeneity in symptom profiles and treatment response.

Clinical Efficacy and Cost-Effectiveness of Imagery Rescripting Only Compared to Imagery Rescripting and Schema Therapy in Adult Patients With PTSD and Comorbid Cluster C Personality Disorder: Study Design of a Randomized Controlled Trial.

Background: Posttraumatic stress disorder (PTSD) is a serious and relatively common mental disorder causing a high burden of suffering. Whereas evidence-based treatments are available, dropout and non-response rates remain high. PTSD and Cluster C personality disorders (avoidant, dependent or obsessive-compulsive personality disorder; CPD) are highly comorbid and there is evidence for suboptimal treatment effects in this subgroup of patients. An integrated PTSD and CPD treatment may be needed to increase treatment efficacy. However, no studies directly comparing the efficacy of regular PTSD treatment and treatment tailored to PTSD and comorbid CPD are available. Whether integrated treatment is more effective than treatment focused on PTSD alone is important, since (1) no evidence-based guideline for PTSD and comorbid CPD treatment exists, and (2) treatment approaches to CPD are costly and time consuming. Present study design describes a randomized controlled trial (RCT) directly comparing trauma focused treatment with integrated trauma focused and personality focused treatment. Methods: An RCT with two parallel groups design will be used to compare the clinical efficacy and cost-effectiveness of "standalone" imagery rescripting (n = 63) with integrated imagery rescripting and schema therapy (n = 63). This trial is part of a larger research project on PTSD and personality disorders. Predictors, mediators and outcome variables are measured at regular intervals over the course of 18 months. The main outcome is PTSD severity at 12 months. Additionally, machine-learning techniques will be used to predict treatment outcome using biopsychosocial variables. Discussion: This study protocol outlines the first RCT aimed at directly comparing the clinical efficacy and cost-effectiveness of imagery rescripting and integrated imagery rescripting and schema therapy for treatment seeking adult patients with PTSD and comorbid cluster C personality pathology. Additionally, biopsychosocial variables will be used to predict treatment outcome. As such, the trial adds to the development of an empirically informed and individualized treatment indication process. Clinical Trial registration: ClinicalTrials.gov, NCT03833531.

Neural correlates of treatment effect and prediction of treatment outcome in patients with PTSD and comorbid personality disorder: study design.

BACKGROUND: Neural alterations related to treatment outcome in patients with both post-traumatic stress disorder (PTSD) and comorbid personality disorder are unknown. Here we describe the protocol for a neuroimaging study of treatment of patients with PTSD and comorbid borderline (BPD) or cluster C (CPD) personality disorder traits. Our specific aims are to 1) investigate treatment-induced neural alterations, 2) predict treatment outcome using structural and functional magnetic resonance imaging (MRI) and 3) study neural alterations associated with BPD and CPD in PTSD patients. We hypothesize that 1) all treatment conditions are associated with normalization of limbic and prefrontal brain activity and hyperconnectivity in resting-state brain networks, with additional normalization of task-related activation in emotion regulation brain areas in the patients who receive trauma-focused therapy and personality disorder treatment; 2) Baseline task-related activation, together with structural brain measures and clinical variables predict treatment outcome; 3) dysfunction in task-related activation and resting-state connectivity of emotion regulation areas is comparable in PTSD patients with BPD or CPD, with a hypoconnected central executive network in patients with PTSD+BPD. METHODS: We aim to include pre- and post-treatment 3 T-MRI scans in 40 patients with PTSD and (sub) clinical comorbid BPD or CPD. With an expected attrition rate of 50%, at least 80 patients will be scanned before treatment. MRI scans for 30 matched healthy controls will additionally be acquired. Patients with PTSD and BPD were randomized to either EMDR-only or EMDR combined with Dialectical Behaviour Therapy. Patients with PTSD and CPD were randomized to Imaginary Rescripting (ImRs) or to ImRs combined with Schema Focused Therapy. The scan protocol consists of a T1-weighted structural scan, resting state fMRI, task-based fMRI during an emotional face task and multi-shell diffusion weighted images. For data analysis, multivariate mixed-models, regression analyses and machine learning models will be used. DISCUSSION: This study is one of the first to use neuroimaging measures to predict and better understand treatment response in patients with PTSD and comorbid personality disorders. A heterogeneous, naturalistic sample will be included, ensuring generalizability to a broad group of treatment seeking PTSD patients. TRIAL REGISTRATION: Clinical Trials, NCT03833453 & NCT03833531 . Retrospectively registered, February 2019.