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Psychiatry"],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Early-course psychosis (ECP) exhibits marked heterogeneity in illness trajectories, with a substantial subset of individuals developing progressive symptomatic, cognitive, and functional decline. Although growing evidence implicates blood-brain barrier (BBB) and neurovascular unit (NVU) dysfunction in psychosis spectrum disorders, direct links between longitudinal clinical trajectories and disease-related cellular phenotypes remain insufficiently characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      This protocol describes a standardized stem cell-based framework to model BBB and NVU dysfunction in ECP using induced pluripotent stem cells (iPSCs) derived from peripheral blood mononuclear cells (PBMCs) within a longitudinally characterized clinical cohort. The approach integrates donor-specific\n                      <jats:italic>ex vivo<\/jats:italic>\n                      cellular assays with repeated clinical, cognitive, and functional assessments for up to 5 years. Procedures are detailed for iPSC reprogramming from PBMCs, differentiation of iPSCs to brain microvascular endothelial cells (BMECs) and cortical neurons, and functional assessment of BBB integrity using trans-endothelial electrical resistance (TEER), paracellular permeability, and tight junction protein expression. NVU effects are examined by exposing cortical neurons to BMEC-conditioned media under matched and cross-culture conditions, with quantification of dendritic spine morphology, synaptic puncta, and neuronal activity using micro-electrode arrays. The protocol further incorporates modular mechanistic perturbations, including pharmacological and genetic modulation of matrix metalloproteinase 1 (MMP1), tumor necrosis factor alpha (TNF\u03b1)-related signaling, and evaluation of antipsychotic effects on barrier function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval and informed consent for this study was obtained and the findings will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences.<\/jats:p>\n                  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