NR3C1 and major depressive disorder: While neuron-specific GR deletion results in mild HPA axis dysregulation, anxiety, and depression-like symptoms (149–151), GR deficiency in both the brain and pituitary gland results in hypercortisolemia, HPA axis dysregulation, growth restriction, and neonatal death within 1–2 weeks after birth (175), highlighting the vital role of glucocorticoids in HPA axis development and regulation.