DBP-L is 8 times higher with Bipolar Disorder, but might be invisible to most tests – April 2017

Bipolar Disorder in Youth is Associated with Increased Low Molecular Weight Fraction of Vitamin D Binding Protein

The FASEB Journal, April 2017, vol. 31 no. 1 Supplement 636.2

Brawnie Petrov1, Ayat Aldoori1, Cindy James2, Kefeng Yang1, Guillermo Perez Algorta4, Arpad Samogyi2, Reem Al Awadhi5, Eugene Arnold3, Mary Fristad3, Barbara Gracious3,6 and Ouliana Ziouzenkova1
1 Human Sciences, The Ohio State University, Columbus, OH
2 Mass Spectometry and Proteomics Facility, The Ohio State University, Columbus, OH
3 Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH
4 Division of Health Research, Lancaster University, Lancaster, United Kingdom
5 Department of Medicine and Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland
6 Department of Child and Adolescent Psychiatry and Behavioral Health, Nationwide Children’s Hospital, Columbus, OH

The following text and several charts are online

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 (NFkB) 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 homologue of GMFβ in human plasma is low molecular weight vitamin D binding protein (DBP-L). DBP-L was 8 times more abundant in plasma of BD compared to control participants. DBP-L is a product of enzymatic cleavage, transforming DBP into a macrophage-activating factor.
DBP levels in participants’ plasma were validated using western blot, whereas mono- and polyclonal ELISA did not recognize DBP-L. We found significantly increased levels of total DBP and DBP-L in BD compared to control participants. The DBP responds early to cellular damage by scavenging actin and activating inflammatory cells.
Our data suggest DBP and DBP-L as marker candidates of BD warranting their validation in a larger cohort of adolescent and adult MMD patients.

Figure 4 Increased DBP-L levels in participants with BD

(A, B ) DBP-L (A) and total DBP(B) protein expression levels were quantified based on western blot analysis in serum obtained from participants in control, MMD, and BD groups. Lines represent the values obtained from individual patients. Red line shows the mean value in each group. Group comparison was measured using ANOVA one-way analysis.

Support or Funding Information
The project was supported by NIH grants R01 MH073801 (M.F., L.E.A.), R21OD017244 (O.Z., B.P., X.L.), the National Center for Research Resources UL1RR025755, UL1TR001070, and NCI P30CA16058 (OSUCCC), and the NIH Roadmap for Medical Research. Dr. Gracious’ time and costs of the blood draw, supplies, and vitamin D assays were funded by the NCH/OSU Dept. of Psychiatry and Behavioral Health Jeffrey Research Fellowship and The Research Institute at Nationwide Children’s Hospital, respectively. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.