Claudin-5 and occludin levels in patients with psychiatric disorders - A systematic review

Background: Recent research has underscored the critical role of blood-brain barrier (BBB) integrity in psychiatric disorders, highlighting disruptions in tight junction (TJ) proteins, specifically claudin-5 and occludin. These proteins are pivotal in maintaining the BBB's selective permeability, which is essential forbrain homeostasis. Altered levels of the TJ proteins have been observed in various psychiatric conditions, suggesting potential as biomarkers for the pathophysiology of these disorders. This systematic review synthesizes existing research on the alterations of claudin-5 and occludin levels in the serum of individuals with psychiatric disorders, evaluating their correlation with BBB dysfunction and psychiatric pathophysiology.

Methods: In adherence to the PRISMA guidelines, a comprehensive search strategy was employed, utilizing databases such as PubMed, Google Scholar, Web of Science, and Scopus. The review encompassed studies published between 2000 and 2024 that measured serum claudin-5 and occludin levels of psychiatric patients. Thorough data extraction and synthesis were conducted.

Results: Seventeen studies met the inclusion criteria. Key findings include indications for increased claudin-5 levels in Schizophrenia, Bipolar Disorder, Depression, and Specific learning disorder, and increased occludin levels in ADHD and Autism Spectrum Disorder patients. No significant differences were found in studies of patients with Alcohol Use and Insomnia Disorder.

Conclusions: The review underscores the potential association between altered serum levels of claudin-5 and occludin and psychiatric disorders, supporting their utility as biomarkers for BBB integrity and psychiatric pathophysiology. Further research is essential to elucidate the mechanisms linking TJ protein alterations with pathophysiology and, potentially, neuroprogression in psychiatric disorders, which could lead to novel diagnostic and therapeutic strategies.