Exploring the interaction between vitamin D pathway gene polymorphisms, vitamin D status, and depression: A population-based study.

Background: The association between vitamin D and depression is controversial, mainly because of genetic differences and confounding factors.

Objective: To evaluate the association between vitamin D and depressive symptoms, considering the influence of genetic variations, skin color, and lifestyle.

Methods: This population-based cross-sectional study was conducted during the COVID-19 pandemic. Depressive symptoms were assessed using the Patient Health Questionnaire-9. Vitamin D deficiency was defined as levels of <20 ng/mL in healthy individuals or <30 ng/mL in at-risk groups. A genetic risk score for vitamin D deficiency was developed based on gene polymorphisms involved in vitamin D metabolism (DHCR7, GC, and VDR), and this score was categorized into tertiles.

Results: Among 1637 participants, 50.9% were women, with a mean age of 42.9 years (95% CI: 41.62-44.26). No association was found between vitamin D deficiency and depressive symptoms. However, the interaction analysis between vitamin D deficiency and the genetic risk score in the subgroups revealed disparities. Individuals with non-white skin color and vitamin D deficiency in the third tertile, supplement non-users with vitamin D deficiency in the second and third tertiles, and participants with insufficient sun exposure and vitamin D deficiency in the second and third tertiles had a higher prevalence of depressive symptoms.

Conclusion: Vitamin D deficiency is linked to a higher prevalence of depressive symptoms in genetically predisposed Brazilians with non-white skin, no vitamin D supplementation, and insufficient sun exposure. Mental health guidelines should aim to promote lifestyle modifications among individuals who are predisposed to depressive symptoms.