Mental Health
The Association between 25-Hydroxyvitamin D Levels and Depression 5 years later: A Longitudinal and Mendelian Randomization Analysis of Canadian Longitudinal Study on Aging data Karen Davison* Karen Davison Davison Davison Davison Davison Davison University of Toronto
Depression is a major global health concern. Although vitamin D is involved in central nervous system functioning, its relationship with depression is unclear. Using data from the Canadian Longitudinal Study on Aging, we examined observational and potential causal associations between serum 25-hydroxyvitamin D (25(OH)D) levels (nmol/L) and depression in a prospective cohort of Caucasian adults aged 45–85 who were not taking vitamin D supplements. The variables included: 1) Depression (outcome) measured using the Center for Epidemiologic Studies Short Depression rating scale (score≥10=depression); 2) Transformed 25(OH)D (to remove seasonal effects, 25(OH)D measures were rescaled using a range from 0-lowest to 1-highest level, and the rescaled values were then square-root transformed to satisfy the normality assumptions required for model fitting); and 3) sociodemographic and health-related variables. The causal association between transformed 25(OH)D and depression were investigated using Two Stage Residual Inclusion methodology.
The prevalence of depression at baseline was 13.8% (n = 9,954). At follow-up 1 (approximately four years after baseline) and in Autumn 2020, the proportions of recurrent or incident depression were 12.3% (n = 9,954) and 19.0% (n = 6,608), respectively. Observational association of transformed 25(OH)D were negatively associated with depression at baseline (OR = 0.35, 95% CI: 0.22–0.54), incident depression at follow-up 1 (OR = 0.28, 95% CI: 0.15–0.52), and incident depression in Autumn 2020 (OR = 0.37, 95% CI: 0.19–0.74). In addition, genetically predicted transformed 25(OH)D were negatively associated with baseline depression (OR = 5.9 × 10⁻⁶, 95% CI: 5.9 × 10⁻¹⁰–1.4 × 10⁻²), incident depression at follow-up 1 (OR = 0.26, 95% CI: 0.13–0.51), and incident depression in Autumn 2020 (OR = 0.43, 95% CI: 0.13–1.40). Three genetic variants, rs2012736 (UGT1A), rs4121823 (LIPG), and rs6013897 (CYP24A1; LD2.1/RP2.2) were found to be related to depression via transformed 25(OH)D.
The findings suggest a potentially causal inverse association between transformed 25(OH)D levels and depression. Future studies could help confirm if vitamin D supplementation may help manage depression in those with genetically low levels of 25(OH)D.