2021). As nicorandil has well‐documented antioxidant property, we hypothesized that it may mitigate depression after TBI by attenuating hippocampal ferroptosis. A key mechanism in preventing ferroptosis involves the SLC7A11/glutathione peroxidase 4 (GPX4) (Chen, Li, et al. 2021), which enhances cystine uptake and promotes glutathione (GSH) synthesis, enabling GPX4 to inhibit lipid peroxidation and inhibit ferroptosis (Chen, Yu, et al. 2021). This evidence concerns the gene GPX4 and major depressive disorder.