Treatment-resistant and drug-free depressed patients had both increased inflammasome activation (higher P2RX7 and proinflammatory cytokines/chemokines mRNAs expression) and glucocorticoid resistance (lower GR and higher FKBP5 mRNAs expression), while responsive patients had an intermediate phenotype with lower CXCL12. Six mRNAs (P2RX7, IL-1-beta, IL-6, TNFα, CXCL12, and GR) distinguished treatment-resistant from responsive patients, even after adjusting for other variables that were different between groups. Here, NR3C1 is linked to glucocorticoid resistance.