Hu et al. reported that chronic variable mild stress (CVMS) induced anxiety- and depression-like behaviors and increased neuronal excitability of ovBNSTCRF neurons and that intra-ovBNST injection of R121919, a CRFR1-selective antagonist, ameliorated the CVMS-induced anxiety- and depression-like behaviors [9]. This evidence concerns the gene CRHR1 and major depressive disorder.