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

• Vitamin d is known to play a pivotal role in depression. However the two independent metabolites, 25(OH)D 3 and 25(OH)D 2 have totally different associations with depression. • Serum 25(OH)D 3 level has an inverse linear association with depressive symptoms in US females. • The association between 25(OH)D 2 and depression follows an inverted U-shaped curve. 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 D 3 (25(OH)D 3) and D 2 (25(OH)D 2) 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)D 3 and 25(OH)D 2 levels were measured using liquid chromatography-tandem mass spectrometry. Linear regression and generalized additive models were applied to evaluate the associations between 25(OH)D 3 , 25(OH)D 2 and depression. A negative association between serum 25(OH)D 3 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)D 2 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)D 2 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)D 3 and depressive symptoms in US females. The association between 25(OH)D 2 and depression follows an inverted U-shaped curve with the inflection point at 56.2 nmol/L. [ABSTRACT FROM AUTHOR]