Vitamin D Deficiency and Mood Disorders among Female Patients with Systemic Lupus Erythematosus: An Electronic Health Record Study

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with multisystem involvement and significant psychiatric comorbidity, including anxiety and depression. Vitamin D, beyond its role in calcium homeostasis, has immunomodulatory and neuropsychiatric effects. Prior research suggests a potential link between vitamin D deficiency and mood disorders, particularly in chronic inflammatory conditions such as SLE. This study investigates the association between vitamin D deficiency and the development of anxiety and depression in female patients with SLE.

Using the TriNetX platform, a multi-institutional electronic health record database, we identified female SLE patients aged 18–52 with and without vitamin D deficiency. Individuals with prior diagnoses of anxiety or depression before SLE onset were excluded. Cohorts were propensity score–matched by age, race, and ethnicity (n = 6,823). The primary outcomes were incident diagnoses of anxiety-related disorders and depressive episodes following SLE diagnosis. Statistical analyses included logistic regression to estimate odds ratios (ORs) and Cox proportional hazards models to calculate hazard ratios (HRs). Scaled Schoenfeld residuals were used to evaluate the proportional hazards assumption.

Each cohort included 6,823 patients. Demographics were well-balanced across cohorts. Patients with vitamin D deficiency had significantly higher odds of anxiety (OR 0.464; 95% CI, 0.411–0.523) and depression (OR 0.517; 95% CI, 0.446–0.599) compared to those without deficiency. Time-to-event analysis showed reduced risk of developing anxiety (HR 0.605; 95% CI, 0.539-0.679) and depression (HR 0.592; 95% CI, 0.513-0.684) in the vitamin D sufficient group.

Our findings demonstrate that vitamin D deficiency is associated with a significantly higher prevalence of anxiety and depression in women with SLE. The biological plausibility for this relationship is supported by vitamin D’s immunomodulatory and neuroprotective effects, including its role in suppressing pro-inflammatory cytokines such as IL-6 and TNF-α, modulating microglial activity, and enhancing serotonergic function. These mechanisms may be especially relevant in SLE, a condition already marked by chronic systemic inflammation and cytokine dysregulation.

Vitamin D deficiency appears to be significantly associated with increased odds and the time to development of anxiety and depression in SLE patients. However, its predictive role over time remains uncertain. These findings highlight the potential value of vitamin D as a modifiable factor in the mental health management of autoimmune diseases. Future prospective studies and randomized controlled trials are warranted to evaluate causality and the therapeutic benefit of vitamin D supplementation in this population.