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

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.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.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.The study used a cross-sectional approach, so causation cannot be determined.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.