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

Abstract

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.

Keywords: 25-hydroxyvitamin D(2); 25-hydroxyvitamin D(3); Depressive symptoms; Females; NHANES.