Hypothesis – Bipolar disorder diagnose based on results of vitamin D-binding protein test – March 2018

Bipolar disorder in youth is associated with increased levels of vitamin D-binding protein

Transl Psychiatry. 2018; 8: 61, online 2018 Mar 13. doi: 10.1038/s41398-018-0109-7
PMCID: PMC5847532. PMID: 29531242
Brawnie Petrov,1 Ayat Aldoori,1 Cindy James,2 Kefeng Yang,1,3 Guillermo Perez Algorta,4 Aejin Lee,1 Liwen Zhang,2 Tao Lin,5 Reem Al Awadhi,6 Jonathan R. Parquette,5 Arpad Samogyi,2 L. Eugene Arnold,7 Mary A. Fristad,#7 Barbara Gracious,#7,8 and Ouliana Ziouzenkova

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Genetic, dietary, and inflammatory factors contribute to the etiology of major mood disorders (MMD), thus impeding the identification of specific biomarkers to assist in diagnosis and treatment. We tested association of vitamin D and inflammatory markers in 36 adolescents with bipolar disorder (BD) and major depressive disorder (MDD) forms of MMD and without MMD (non-mood control). We also assessed the overall level of inflammation using a cell-based reporter assay for nuclear factor kappa-B (NFκB) activation and measuring antibodies to oxidized LDL. We found that these factors were similar between non-mood and MMD youth. To identify potential biomarkers, we developed a screening immunoprecipitation-sequencing approach based on inflammatory brain glia maturation factor beta (GMFβ). We discovered that a homolog of GMFβ in human plasma is vitamin D-binding protein (DBP) and validated this finding using immunoprecipitation with anti-DBP antibodies and mass spectrometry/sequencing analysis. We quantified DBP levels in participants by western blot.
DBP levels in BD participants were significantly higher (136%) than in participants without MMD (100%).
The increase in DBP levels in MDD participants (121.1%) was not statistically different from these groups. The DBP responds early to cellular damage by binding of structural proteins and activating inflammatory cells. A product of enzymatic cleavage of DBP has been described as macrophage-activating factor. Circulating DBP is comprised of heterogenous high and low molecular fractions that are only partially recognized by mono- and polyclonal ELISA and are not suitable for the quantitative comparison of DBP in non-mood and MDD participants. Our data suggest DBP as a marker candidate of BD warranting its validation in a larger cohort of adolescent and adult MMD patients.