Furthermore, while general anti-inflammatory drugs may indirectly affect the KP by reducing pro-inflammatory cytokines that drive IDO1 expression, our study provides direct evidence that H2S specifically modulates this pathway, potentially through a mechanism that suppresses upstream hippocampal necroptosis, positioning H2S as a unique therapeutic candidate capable of simultaneously targeting the core pathological axis of neuroinflammation and metabolic dysregulation in depression. This evidence concerns the gene IDO1 and major depressive disorder.