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.

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.