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.