Image: The Synergy H1 Hybrid Multi-Mode Microplate Reader (Photo courtesy of BioTek).
Major mood disorders (MMD), specifically bipolar disorder (BD) and major depressive disorder (MDD), are some of the most prevalent albeit under-diagnosed health problems in children and adolescents. Worldwide among adolescents, MDD and BD are the first and fourth most disabling conditions, respectively.
A blood test may have the potential to speed accurate diagnosis and proper treatment of bipolar disorder in children. It has been reported that children with bipolar disorder had higher blood levels of a protein associated with vitamin D compared to children without mood disorders. A blood test to confirm bipolar disorder could improve care and cut the current 10-year average lag time between onset and diagnosis.
Scientists from the Ohio State University (Columbus, OH, USA) collected plasma samples from 36 participants in a study that were grouped into three categories: 13 non-mood controls, 12 bipolar (BD) and 11 major mood disorders (MDD). Concentrations of inflammatory cytokine interleukin-6 (IL-6), autoantibodies to oxidized low-density lipoprotein (oxLDL), and vitamin D in serum as well as serum nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activity were measured and analyzed in conjunction with metabolic characteristics (body mass index (BMI)).
Vitamin D (25-hydroxycalciferol and 25-hydroxyergocalciferol) analysis on serum was performed by high-pressure liquid chromatography (HPLC) coupled with mass spectrometry (MS) detection. The cumulative NFκB activation potential of plasma was measured using NF-κB/green fluorescence protein biosensor assay on a Synergy H1 Hybrid Multi-Mode Microplate Reader. IL-6 serum concentrations were analyzed using Immulite 1000 IL-6 assay. Human IgG autoantibodies to oxidized low-density lipoproteins (oxLDL) in serum were measured using an Anti-Oxidized LDL (oLAB) ELISA Kit.
To identify potential biomarkers, the team developed a screening immunoprecipitation-sequencing approach based on inflammatory brain glia maturation factor beta (GMFβ). They 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. They quantified DBP levels in participants by western blot. DBP levels in BD participants were significantly higher than in participants without MMD. DBP measured by monoclonal ELISA also showed no correlation with vitamin D concentration in serum in non-mood control. However, in MDD participants, but not in BD participants DBP levels recognized by polyclonal ELISA were inversely associated with vitamin D levels.
The authors concluded that DBP holds promise as a diagnostic biomarker changing in response to all major factors contributing to pathogenesis of BD, and may shed light on BD pathophysiologic mechanisms. Barbara L. Gracious, MD, associate professor of clinical psychiatry and nutrition and a lead study co-author, said, “Childhood bipolar disorder can be very difficult to distinguish from other disorders, especially in youth with certain types of depression. Prompt diagnosis and appropriate treatment alleviates the suffering of the child and family, and can potentially lessen the risk for suicide.” The study was published on March 13, 2018, in the journal Translational Psychiatry.
Ohio State University