Effect of metacognitive interpersonal therapy on brain structural connectivity in borderline personality disorder: Results from the CLIMAMITHE randomized clinical trial

Background: Recently, we showed that Metacognitive Interpersonal Therapy (MIT) is effective in improving clinical symptoms in borderline personality disorder (BPD). Here, we investigated whether the effect of MIT on clinical features is associated to microstructural changes in brain circuits supporting core BPD symptoms. Methods: Forty-seven BPD were randomized to MIT or structured clinical management, and underwent a clinical assessment and diffusion-weighted imaging before and after the intervention. Fractional anisotropy (FA), mean, radial, and axial diffusivities maps were computed using FSL toolbox. Microstructural changes were assessed (i) voxel-wise, with tract based spatial statistics (TBSS) and (ii) ROI-wise, in the triple network system (default mode, salience, and executive control networks). The effect of MIT on brain microstructure was assessed with paired tests using FSL PALM (voxel-wise), Linear Mixed-Effect Models or Generalized Linear Mixed Models (ROI-wise). Associations between microstructural and clinical changes were explored with linear regression (voxel-wise) and correlations (ROI-wise). Results: The voxel-wise analysis showed that MIT was associated with increased FA in the bilateral thalamic radiation and left associative tracts (p < .050, family-wise error rate corrected). At network system level, MIT increased FA and both interventions reduced AD in the executive control network (p = .05, uncorrected). Limitations: The DTI metrics can't clarify the nature of axonal changes. Conclusions: Our results indicate that MIT modulates brain structural connectivity in circuits related to associative and executive control functions. These microstructural changes may denote activity-dependent plasticity, possibly representing a neurobiological mechanism underlying MIT effects. Trial registration: ClinicalTrials.gov NCT02370316 (https://clinicaltrials.gov/study/NCT02370316).