Vitamin D Deficiency Is Associated With Increased Depression Risk in Obese Asthma.

BACKGROUND

Asthma is frequently accompanied by depression, but whether vitamin D deficiency increases the risk of depression remains unclear.

OBJECTIVE

To examine the association between serum 25-hydroxyvitamin D (25[OH]D) and depression in adults with asthma, with particular attention to the role of overweight and obesity, and to explore potential mechanisms using genetic and transcriptomic evidence.

METHODS

Using the National Health and Nutrition Examination Surveys 2007 to 2018 and 2021 to 2023, we applied logistic regression to assess associations between 25(OH)D strata and depression with stratification by body mass index (BMI). Two-sample Mendelian randomization tested causal relationships among 25(OH)D, asthma, depression, and BMI. Transcriptomic differentially expressed genes were integrated with disease-related genes for pathway enrichment.

RESULTS

A total of 4,890 adults with asthma were included. Lower 25(OH)D levels showed a graded association with the risk of depression. Compared with sufficient 25(OH)D (≥75 nmol/L), insufficiency (50-74.9 nmol/L), mild deficiency (25-49.9 nmol/L), and severe deficiency (<25 nmol/L) were associated with approximately 40%, 73%, and 97% higher risks of depression (all P < .05). This association was observed only in the overweight and obese subgroup (odds ratio = 1.46; 95% CI, 1.15-1.86; P interaction = .285). Mendelian randomization analyses did not support a genetic causal effect of 25(OH)D on asthma or depression, whereas BMI showed positive causal effects on both. Transcriptomic analysis identified 69 core candidate genes enriched in the TH17-neutrophil axis.

CONCLUSIONS

Vitamin D deficiency was associated with higher odds of depression in asthma, reaching significance only in the overweight and obese subgroup, although the interaction was not significant. This association may involve the TH17/neutrophil inflammatory axis rather than direct genetic causality, supporting attention to vitamin D status and mental health in patients with asthma who are overweight or obese.