Investigating changes in the blood-brain barrier in schizophrenia spectrum disorders: design and methodology of a...

Schizophrenia spectrum disorders (SSDs) are clinically and biologically heterogeneous and lack reliable biomarkers for stratification, treatment response and course prediction. Evidence from postmortem, fluid biomarker, and neuroimaging studies suggests that changes in the blood-brain barrier (BBB) may contribute to pathophysiology in a biologically defined subgroup. However, findings in this context are inconsistent and often based on cross-sectional or indirect measures. This 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 at V1. DCE-MRI-derived voxel-wise permeability metrics are then analyzed. Primary objectives are to compare BBB leakage cross-sectionally between SSD and HC. Secondary objectives include (i) characterizing spatial and temporal leakage profiles across illness phases, (ii) 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, the IMPACT study aims to elucidate BBB alterations in SSDs and to support stratification approaches in precision psychiatry.