Clinical Significance and Changes in Levels of Serum BDNF, mBDNF, AQP4, proBDNF, and GSK3β in Individuals Diagnosed With Bipolar Disorder: A Cross-Sectional Study.

BACKGROUND AND AIMS: Bipolar disorder (BD) is a severe mood disorder with unclear pathogenesis and limited diagnostic biomarkers. This study aimed to evaluate serum levels of BDNF, mBDNF, AQP4, proBDNF, and GSK3β between BD patients and healthy controls, and to preliminarily explore their potential clinical significance. METHODS: Thirty-seven patients admitted to the Affiliated Hospital of Hangzhou Normal University with BD from November 2023 to September 2025 were selected as the study subjects, while 36 healthy blood donors from the Affiliated Hospital of Hangzhou Normal University, collected in April 2025, were selected as the control subjects to compare serum biomarkers levels of the two groups. Receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic value of serum biomarkers levels for bipolar disorder. Correlations between serum biomarkers were analyzed between the two groups. RESULTS: The results revealed lower levels of BDNF and AQP4 and higher levels of mBDNF, proBDNF and GSK3β in the BD group compared to the healthy control group. Positive correlations were observed between serum BDNF and proBDNF, mBDNF and AQP4, as well as mBDNF and GSK3β levels in the BD group. Combining the serum biomarkers improved diagnostic accuracy compared to using individual serum biomarkers alone. CONCLUSION: In conclusion, patients with BD exhibit elevated serum levels of proBDNF and GSK3β compared to healthy controls, while the levels of BDNF, mBDNF, and AQP4 are significantly lower. These findings suggest that this serum biomarker panel may hold preliminary potential as a supportive indicator for BD. However, given the study's cross-sectional design and lack of external validation, larger longitudinal cohorts are required to further evaluate its potential clinical significance.