Improvement of Depressive Symptoms upon Correction of Vitamin D Deficiency in Women with Chronic Liver Disease

Introduction: Patients with chronic liver diseases (CLD) frequently suffer from both vitamin D deficiency and depression. A recent meta-analysis reported an inverse correlation between depression and vitamin D levels. Indeed, vitamin D receptor (VDR) is present and genomic and nongenomic VDR-mediated signalling has been identified in brain. As depression is known to occur more frequently in women than in men, this intervention study investigates the differential effects of vitamin D substitution on depressive symptoms in patients with CLD and depression.

Methods: Vitamin D insufficiency (as defined by serum concentrations < 30 ng/ml) was present in 77 (79%) of patients with CLD recruited in the overall study. From these, 31% had depressive symptoms as assessed using the BDI-II instrument (score ≥ 14 indicating depression) and were included in the sensitivity analyses herein. Serum 25-hydroxyvitamin D concentrations were determined by chemiluminescence immunoassays. All patients received 20,000 IU vitamin D/week for 6 months. We assessed liver function tests (LFT), vitamin D status and depression after 3, 6, and 12 months during follow-up.

Results: The median age of the patients with CLD and depressive symptoms was 56 years, 60% were women, and 42% had chronic hepatitis C virus (HCV) infection. Men and women with depression and vitamin D insufficiency did not differ (all P > 0.05) with respect to age, body mass index, LFT, 25-hydroxyvitamin D levels (14 vs.17 ng/ml) and BDI-II scores (18 vs. 21 points) at baseline. A significant inverse linear correlation between vitamin D level and depression severity existed in women only (rs=-0.55, P= 0.026). Vitamin D levels significantly (P < 0.001) increased to normal after 3 and 6 months of supplementation in all CLD patients, but higher median 25-hydroxyvitamin D levels were consistently displayed in women. Interestingly, during the intervention period, a distinct response was observed in women with BDI-II scores returning to normal levels at 3 and 6 months (13 and 11 points, respectively; both P= 0.002), whereas no change in depression scores was observed in men (18 and 19 points, respectively). LFT remained unchanged with vitamin D supplementation.

Conclusions: In patients with CLD, marked gender disparities are observed with regards the association between vitamin D and depressive symptoms herein, with only women showing an inverse relationship between vitamin D levels and depressive symptoms. Moreover, vitamin D therapy significantly improved depressive symptoms to normal levels in women as compared to men with CLD and vitamin D insufficiency. The functional mechanisms underlying these gender disparities in response to vitamin D substitution in CLD warrant further investigation.

Corresponding author: Stokes, Caroline S

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