Abstract
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.