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. • Preclinical evidence supports antidepressant-like effects of vitamin D signaling. • Vitamin D signaling mediates antidepressant-like effects via antioxidant, anti-inflammatory, pro-neuroplastic, and monoaminergic pathways. • Vitamin D signaling mechanisms occur in mood-regulating brain regions.
Camargo et al. (Sun,) studied this question.