NR3C1 and major depressive disorder: The underlying mechanism of depression was suggested to be mediated by chronic hypercortisolemia, which results in excessive release of reactive oxygen species (ROS), increased NF-B transcriptional activity, and decreased synthesis of neurotrophic factors in many glucocorticoid receptor rich brain areas, such as the prefrontal cortex, amygdala, and hippocampus, with subsequent induction of structural and functional deficits.