Integrated alterations in inflammation, endothelial function, and extracellular matrix pathways in first-episode drug-naïve schizophrenia

Schizophrenia (Heidelb). 2026 May 14. doi: 10.1038/s41537-026-00766-7. Online ahead of print.

ABSTRACT

Objective peripheral biomarkers for early-stage schizophrenia are needed to improve diagnostic accuracy and treatment planning. To identify potential biomarkers, we compared multiple serum factor concentrations between 90 first-episode drug-naïve patients and healthy matched controls, and further examined associations with symptom severity and cognitive functions among patients. Serum interleukin (IL)-8, vascular cell adhesion molecule (VCAM)-1, matrix metalloproteinase (MMP)-2, and MMP-7 concentrations were quantified by Luminex multiplex immunoassays, and log10-transformed values compared with adjustment for age, sex, years of education, body mass index, and smoking status. Associations with symptoms as assessed by the Positive and Negative Syndrome Scale (PANSS) and cognitive functions as assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were examined by Pearson’s correlation analysis. Multivariable logistic regression models were developed for case-control discrimination by receiver operating characteristic analysis with 10-fold cross-validation and calibration. Serum log10[IL-8] and log10[MMP-7] were higher while serum log10[MMP-2] and log10[VCAM-1] were lower in patients. Serum log10[MMP-2], log10[MMP-7], and log10[VCAM-1] were positively correlated among patients, whereas log10[IL-8] was not associated with this MMP/VCAM-1 axis. There were no stable linear associations with PANSS or RBANS scores. Serum log10[IL-8] demonstrated the highest single-marker discrimination (AUC = 0.742, 95%CI: 0.667-0.817), and the four-biomarker model further improved discrimination (AUC = 0.839, 95%CI: 0.781-0.897; 10-fold cross-validated AUC = 0.804). A Youden-derived threshold of 0.518 yielded 78.9% sensitivity and specificity for distinguishing cases. A serum inflammation-endothelium-extracellular matrix biomarker panel showed good discriminative performance in distinguishing first-episode drug-naïve schizophrenia from controls in a case-control sample; external validation and potential recalibration in real-world cohorts are warranted.

PMID:42135356 | DOI:10.1038/s41537-026-00766-7