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

Abstract

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.

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

“…Other psychotropic medication needed to be stable for at least three weeks prior to study participation. In this study, we used a subset of data of participants from the PROSPER-trials that agreed to the scanning sessions, see Aarts et al (2021) . We recruited 88 participants with PTSD for the current study.…”

“…We screened participants for the PROSPER trial with the Structured Clinical Interview for DSM-5 Personality Disorders (SCID-5-PD), a semi-structured interview to assess personality disorders ( Arntz et al, 2017 , First et al, 2016 ). Based on the SCID-5-PD, we included participants in the PTSD + BPD trial or the PTSD + CPD trial, see Aarts et al (2021) . For the current study, we classified participants who fulfilled full criteria for both BPD and CPD in the PTSD + BPD + CPD group.…”

“…Prior to the scanning session, participants filled out a medication list to assess medication use in the previous 24 h. In a separate appointment, there was a clinical interview to assess PTSD symptoms and participants filled out questionnaires online. The full scanning protocol can be found in Aarts et al (2021) . Control participants came to the location once for the MRI scan and two neuropsychological tests.…”

“…Our main contrast of interest was the fearful faces vs scrambled faces, secondary contrasts are angry vs scrambled and neutral vs scrambled. See Aarts et al (2021) for more details. Task performance was calculated as proportion of correct responses.…”

Improving treatment outcomes for borderline personality disorder: what can we learn from biomarker studies of psychotherapy?

“…DBT remains the most commonly studied psychotherapy ( n = 15), represented in nearly 70% of studies. Future planned studies incorporating neurobiological measures [43 ▪ ,44,45 ▪ ] and psychotherapies beyond the usual DBT [46] offer promise. Future work along these lines has the potential to contribute a neurobiological perspective to the question of whether psychotherapy outcomes in BPD relate to common factors vs. specific mechanisms across different theoretical approaches [47,48].…”