Vitamin C Reverses Depression-Like Behavior in Female Mice via D2 Receptors

Major depressive disorder disproportionately affects women, yet treatment options for female-specific conditions like perinatal depression remain limited by delayed efficacy and adverse side effect profiles. Emerging clinical evidence increasingly links oxidative stress (a cellular imbalance between reactive oxygen species and antioxidant defenses) to the pathophysiology of depression, prompting renewed interest in antioxidant therapies [1, 2]. Ascorbic acid, commonly known as vitamin C, demonstrates neuromodulatory properties that improve mood and alleviate depressive symptoms; for example, a crossover trial of 48 women showed that 150 mg of ascorbic acid combined with 100 mg of oxaloacetate reduced premenstrual depression scores by 54.1% and anxiety by 51.4% [3]. Furthermore, an ongoing randomized controlled trial of 424 patients is exploring whether ascorbic acid can synergize with rapid-acting antidepressants like esketamine to mitigate post-miscarriage psychiatric vulnerabilities [4]. Building on this clinical foundation, a recent preclinical study in female mice demonstrated that a single 200 mg/kg dose of ascorbic acid rapidly reversed stress-induced transcriptional alterations in 104 genes within the medial prefrontal cortex, specifically restoring the dopamine D2 receptor pathway to exert antidepressant effects within 24 hours [5].