In conclusion, the identification of p21 as a hub gene interacting with oxidative stress-associated DEGs sheds light on potential therapeutic targets and signaling pathways that could be modulated to mitigate the adverse effects of chronic stress or prolonged CORT exposure (such as in Cushing’s syndrome-endogenous GCs or when using high doses of exogenous GCs) on hippocampus structure and function. Here, CDKN1A is linked to Cushing syndrome.