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Serum levels of coagulation factor IX (F9) and complement factor H (CFH) are significantly elevated in patients with bipolar disorder when measured by targeted multiple reaction monitoring, though their clinical utility as biomarkers remains unproven. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

June 28, 2026Open Access

Targeted Quantification of Complement–Coagulation Proteins in Bipolar Disorder: Comparison of Multiple Reaction Monitoring and Enzyme-linked Immunosorbent Assay

Key Points

This research aims to quantify complement-coagulation proteins in bipolar disorder to identify potential biomarkers.
Measured serum levels of F9, CFH, and VTDB in bipolar disorder patients (n=8) and healthy controls (n=19) using MRM and ELISA.
Employed Spearman correlation analysis and linear regression, adjusting for age and body mass index using Quade's analysis of covariance.
Conducted comparison of results from targeted MRM and ELISA methods.
MRM revealed significantly higher levels of F9 and CFH in bipolar disorder patients (p<0.05 for F9 and CFH).
ELISA showed similar trends for F9 and CFH, but differences were not statistically significant.
No significant adjusted group effects were observed for ELISA measurements.

Abstract

Bipolar disorder (BD) remains difficult to diagnose accurately using symptom-based criteria alone, underscoring the need for objective biomarkers.Proteomics studies repeatedly implicate immune-related pathways, particularly the complement-coagulation axis, but targeted verification and orthogonal cross-platform validation remain limited.The levels of three candidate serum proteins-coagulation factor IX (F9), complement factor H (CFH), and vitamin D-binding protein (VTDB)-in BD patients (n=8) and healthy controls (n=19) were quantified using targeted multiple reaction monitoring (MRM) and enzyme-linked immunosorbent assay (ELISA).Group comparisons, Spearman correlation analysis, and linear regression were performed.Demographic imbalances were addressed by applying Quade's nonparametric analysis of covariance with age and body mass index as covariates.MRM measurements revealed significantly higher levels of F9, CFH, and VTDB in BD, whereas ELISA showed changes in the same direction that did not reach statistical significance.After covariate adjustment, MRM-based group effects remained significant for F9 and CFH but not VTDB, while no adjusted group effects were observed for ELISA.Strong positive correlations were observed among MRM measures, and F9 (MRM) was inversely associated with age.These findings suggest MRM-associated alterations in F9 and CFH in BD, but their utility as biomarkers remains unproven.

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