A fifth hypothesis that is not supported by our study suggests that chronically high cortisol levels, and consequent alterations in glucocorticoid-responsive transcription contribute to the pathogenesis of MDD.8, 29, 36, 37, 52, 86, 103, 123, 124, 125, 126, 127, 128, 129, 130 We found no significant alterations in GR-mediated gene expression in control versus untreated MDD subjects, either before or after 8 weeks of antidepressant treatment. The gene discussed is NR3C1; the disease is major depressive disorder.