NLRP3 and major depressive disorder: The therapeutic mechanism likely involves dual modulation of the neuro-immune axis (e.g., NLRP3 inflammasome suppression) and achievement of a threshold serum 25(OH)D level (>30 ng/mL).For clinical practice, we propose an individualized regimen targeting treatment-resistant depression: Dosage: 50,000 IU/week for ≥1 year (target serum 25(OH)D >40 ng/mL).High-priority populations: Patients with metabolic syndrome, seasonal affective disorder, or autoimmune diseases.