Aydoğan Avşar, PınarAkkuş, Merve2026-01-242026-01-2420250940-1334https://doi.org/10.1007/s00406-025-02097-7https://hdl.handle.net/20.500.12868/4552Bipolar disorder is a mental illness with a complex and multidimensional etiology. The blood-brain barrier (BBB) is a semi-permeable barrier between the central nervous system (CNS) and peripheral circulation that protects the CNS from external threats. The healthy functioning of the BBB is ensured by tight junctions (TJs) between cells. This research aims to investigate the serum levels of TJ proteins occludin and zonula occludens-1 protein (ZO-1) in bipolar disorder to elucidate etiopathogenesis. This study included 40 BD patients (20 manic episodes, 20 euthymic episodes) and 40 healthy controls. Serum occludin and ZO-1 values were obtained and compared between the two groups. The serum occludin and ZO-1 levels were significantly higher in the bipolar disorder patients. The analysis of covariance (ANCOVA) revealed a significant main effect of groups in the serum occludin and ZO-1 levels and an effect that was independent of age, gender, BMI, and smoking.BBB disruption and neuroinflammation may play a role in bipolar disorder etiopathogenesis. Occludin and ZO-1 may serve as potential biomarkers for BBB leakage in bipolar disorder. Further research may lead to additional pharmacological therapies targeting BBB for drug-resistant bipolar disorder patients. © Springer-Verlag GmbH Germany, part of Springer Nature 2025.eninfo:eu-repo/semantics/closedAccessBBBBipolar disorderBrain-blood-barrierOccludinTight junction proteinsZO-1Article10.1007/s00406-025-02097-72-s2.0-105014886793Q1