Imaging Blood-Brain Barrier Dysfunction in Schizophrenia Spectrum Disorders: protocol of the longitudinal IMPACT DCE-MRI study

Schizophrenia spectrum disorders (SSDs) are clinically and biologically heterogeneous and lack reliable biomarkers for stratification and outcome prediction. Evidence from postmortem, fluid biomarker, and neuroimaging studies suggests that blood-brain barrier (BBB) dysfunction may contribute to pathophysiology in a biologically defined subgroup. However, findings are inconsistent and often based on cross-sectional or indirect measures. The IMPACT study is a longitudinal, multimodal investigation designed to quantify BBB permeability across disease phases using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and to integrate these measures with deep clinical phenotyping. We recruit inpatients with SSDs and healthy controls (HC). Participants undergo multimodal MRI including DCE-MRI at three time points: acute psychosis (baseline; V1), early treatment (4-6 weeks; V2), and long-term follow-up (2.5 years; V3). Clinical characterization includes standardized measures of psychopathology, functioning and cognition. Blood samples are collected at each visit, while CSF is obtained only when clinically indicated in the SSD group. DCE-MRI-derived voxelwise permeability metrics are then analyzed. Primary objectives are to (i) compare BBB leakage cross-sectionally between SSD and HC and (ii) characterize spatial and temporal leakage profiles across illness phases. Secondary objectives include analyzing associations with psychopathology and biological (e.g., inflammatory) signatures, as well as exploratory identification of subgroups. By providing a longitudinal, BBB-specific neuroimaging framework embedded in a deep phenotyping infrastructure, IMPACT aims to elucidate BBB alterations in SSDs and to support biologically informed stratification approaches in precision psychiatry.