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Evidence from postmortem, fluid biomarker, and neuroimaging studies suggests that changes in the blood\u2013brain 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\u20136 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. 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Figure\n                      \n                      was created with Biorender.com. During the preparation of this work the author(s) used the GPT \u2013 4 model developed by OpenAI in order to improve readability and language of the manuscript. After using this tool, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication. The authors declare that they have no biomedical financial interests or potential conflicts of interest regarding the content of this report. AH received paid speakership by Janssen, Otsuka, Lundbeck, and Recordati and was member of advisory boards of these companies and Rovi. PF received paid speakership by Boehringer-Ingelheim, Janssen, Otsuka, Lundbeck, Recordati, and Richter and was member of advisory boards of these companies and Rovi. EW was invited to advisory boards from Recordati, Teva and Boehringer-Ingelheim. IM has received paid speakership by Boehringer-Ingelheim. BS has received speaker honoraria by Novartis and Chiesi. All other authors report no biomedical financial interests or potential conflicts of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}