Background/Objective: Depression is a widespread and complex disorder, constituting a major public health concern due to its significant impact on mental health. Because of the limitations of major depressive disorder (MDD) treatment, recent research on depression management has focused on identifying new therapeutic strategies. The effects of vitamin D on the brain, mediated through various mechanisms, suggest the potential implication of vitamin D in the pathophysiology of depression. In this systematic review, our objective was to evaluate the correlation between serum levels of 25-hydroxyvitamin D (25(OH)D) and depression based on evidence from cross-sectional and cohort studies. Furthermore, we also assessed the effect of vitamin D supplementation in relation to depressive symptoms, using data from randomised controlled trials (RCTs). Methods: To achieve the proposed objective, we have compiled a report that includes a selection of empirical evidence necessary to review the relationship between vitamin D and depression. In this regard, relevant articles were searched on platforms such as PubMed, MDPI, ResearchGate, Springer Link, Springer Open, and ScienceDirect. A total of 13,976 records, published between 2008 and 2024, were initially identified through database searches. After the study selection process, performed according to the PRISMA guidelines, 70 articles were included in the systematic review. Results: According to most cross-sectional and cohort studies, the results highlight an inverse relationship between serum 25(OH)D levels and the risk of depression, as well as the severity of depressive symptoms. An increase in serum 25(OH)D concentration is associated with an improvement in depression test scores, with vitamin D supplementation exerting a beneficial effect on both the incidence and the prognosis of depression. Conclusions: Based on current evidence which indicates the implications of vitamin D in the neurobiological mechanisms associated with depression, and the results obtained in most of the studies, which demonstrate an inverse relationship between serum 25(OH)D levels and the beneficial effect of vitamin D supplementation on depressive symptoms, vitamin D could represent an adjunctive therapy in the management of MDD. More rigorous studies, without methodological errors, are needed to correctly and definitively assess the impact of vitamin D in relation to depression.

The implication of vitamin D in the pathophysiology of depression has generated interest regarding its role as a biomarker in the context of mental health. Given the limited data on this association in the Romanian population, the present study aimed to evaluate the correlation between vitamin D status and the severity of depressive symptomatology in a sample of adult patients from Romania. This cross-sectional study was conducted on 90 patients diagnosed with major depressive disorder who were admitted to the Department of Psychiatry at the County Clinical Emergency Hospital of Bihor during the period of 2024–2025. Serum vitamin D concentrations were determined by measuring the 25-hydroxyvitamin D metabolite in blood using the chemiluminescence microparticle immunoassay method. The severity of depressive symptomatology was quantified using two validated scales: the Beck Depression Inventory-II (BDI-II) and the Hamilton Depression Rating Scale 17 (HAM-D17). Multivariable linear regression and ordered probit regression were used to assess the relationship between vitamin D status and depression severity, with adjustments for relevant covariates. A statistically significant negative association was identified for the BDI-II scale (B = −0.3170444, β = −0.2621328, p = 0.007) and the HAM-D17 scale (B = −0.1495026, β = −0.2829461, p = 0.002), which remained robust after adjustment for covariates (BDI-II: B = −0.2110473, β = −0.1744942, p = 0.050; HAMD17: B = −0.1153659, β = −0.2183397, p = 0.018). In comparison with subjects with vitamin D deficiency, those with sufficient levels presented a significantly lower probability of belonging to higher severity categories of depression for both scales (BDI-II: coefficient = −0.6855429, p = 0.004; HAM-D17: coefficient = −0.7029572, p = 0.005). The study highlighted a statistically significant negative correlation between vitamin D status and depression severity, which remained after adjustment for covariates. Sufficient vitamin D levels were associated with a significantly lower probability of belonging to a higher depression severity category compared with deficiency.