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

Abstract

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.

Clinical Severity and Calcium Metabolism in Patients with Bipolar Disorder

“…First, PTH levels can influence the levels of chronic neuroinflammation, which is significantly associated with a higher burden of illness and a more severe clinical presentation of the disorder [ 31 ], leading to an altered neurotransmission [ 32 ] and dysfunctional brain development through a reduced induction of the nerve growth factor [ 33 , 34 ], reduced immunoregulation and anti-inflammatory actions [ 35 , 36 ]. Second, the relationship between high PTH levels and age at onset might be due to a chronic Vit D deficiency, that triggers the neuroinflammation process, ultimately resulting in full-blown disease [ 37 , 38 ]. This finding confirms previous evidence that calcium imbalance is associated with an earlier age at onset and with a worse long-term outcome in terms of symptom severity, social functioning and number of relapses and hospitalizations [ 39 ].…”

Vulnérabilité au Trouble Bipolaire: La Piste de la Vitamine D

“…35 Récemment, Petrov et al ont trouvé des taux de VDBP, qui est la protéine de transport de la vitamine D, significativement plus élevés chez les patients TB d'origine afro-américaine par rapport aux sujets de « race blanche ». 8 Concernant cette protéine, il est établi que le complexe 25OHD-VDBP ne peut pas passer la barrière hémato encéphalique. 36 Cependant, selon une étude récente, 37 en cas de pathologies neuro inflammatoires, la VDBP peut passer au LCR et elle a été proposée comme biomarqueur pronostique de la sclérose en plaque.…”

“…6,7 Dans une étude récente menée par Petrov et al en Amérique du nord, les taux plasmatiques de ces deux marqueurs étaient plus élevés chez des patients suivis pour trouble bipolaire (TB) par rapport à des témoins. 8 Vu que la latitude compte parmi les facteurs qui déterminent le taux de vitamine D, 9 il serait intéressant de reproduire cette étude dans d'autres zones géographiques, notamment la région MENA (Middle East-North Africa: MENA) qui constitue l'une des zones où les taux de vitamine D sont les plus bas. 10 A ce sujet, certains auteurs 11 ont fait remarquer qu'aucun des guidelines disponibles concernant les taux sériques recommandés et la supplémentation de vitamine D ne s'est basé sur une revue systématique rigoureuse dans la région MENA.…”

MNAD Hypothesis Based Protocol Proposed for Treatment of COVID.19: Assessment of Minocycline, N. acetylcysteine, Aspirin & vitamin D (MNad) Theory for treatment of COVID.19 Adults Patients

“…Mediating factors include obesity, inactivity, diabetes or metabolic syndrome, and increased inflammatory factors-all with increased prevalence among BD patients [7]. Bipolar disorder in youth associated with increased levels of vitamin D-binding protein [8] and that means low levels of vitamin D. Also increased risk for pulmonary embolism in patients with bipolar disorder was observed [9]. Catatonia which is one of the bipolar spectrum disorders can lead to pneumonia, obstructive nephropathy, azotemia, deep vein thrombosis (DVT), and ultimately pulmonary embolism (PE) [10].…”