Vitamin D in major depressive disorder: Current evidence, possible molecular mechanisms, and future prospects

Vitamin D signaling has emerged as a significant modulator of neurobiological processes implicated in major depressive disorder (MDD). Beyond its classical functions in calcium homeostasis and bone health, accumulating evidence highlights antioxidant, neurotrophic, and anti-inflammatory effects mediated by vitamin D-dependent pathways in the central nervous system. By influencing neurotransmitter synthesis, neuroinflammatory and redox pathways, as well as neuroplasticity, vitamin D signaling may contribute to mechanisms underlying depressive symptoms. Therefore, this review aims to provide a comprehensive overview of preclinical studies examining the association between vitamin D status or vitamin D-related interventions and antidepressant-like effects in rodent models, exploring the molecular mechanisms potentially involved, and highlighting the role of vitamin D-dependent signaling pathways in modulating key neurobiological targets implicated in MDD. It may contribute to establishing the relevance of vitamin D-related mechanisms to MDD pathophysiology and identifying promising targets for future translational studies.