Independent Associations of Serum 25-hydroxyvitamin D3 and D2 with Depressive Symptoms in Females

Background: The role of vitamin D in depression has been gaining increased research interest. However, little is known about the independent associations of serum 25-hydroxyvitamin D3 (25(OH)D3) and D2 (25(OH)D2) with depressive symptoms. The goal of this study was to examine the metabolites of vitamin D and their associations with depression. Methods: This study was conducted in US females using data from the National Health and Nutrition Examination Survey 2011-2014. Depressive symptoms were assessed using a nine-item Patient Health Questionnaire, and serum 25(OH)D3 and 25(OH)D2 levels were measured using liquid chromatography-tandem mass spectrometry. Linear regression and generalized additive models were applied to evaluate the associations between 25(OH)D3, 25(OH)D2 and depression. Results: A negative association between serum 25(OH)D3 and depressive symptoms was observed in the fully adjusted model. This association was also found among widowed, divorced, separated, and never-married individuals. The association between 25(OH)D2 and depressive symptoms was not statistically significant, but the dose-response analysis revealed an inverted U-shaped relationship between them with an inflection point at 56.2 nmol/L. To the left of the inflection point, we detected a positive association between 25(OH)D2 and depressive symptoms, whereas a negative association was observed to the right of the inflection point. Limitations: The study used a cross-sectional approach, so causation cannot be determined. Conclusions: Our study shows an inverse linear association between serum 25(OH)D3 and depressive symptoms in US females. The association between 25(OH)D2 and depression follows an inverted U-shaped curve with the inflection point at 56.2 nmol/L.