Taken together, recent studies using conditional mutagenesis or viral knock-down or overexpression of CRF system components strongly indicate that the involvement of CRF system components in stress-associated anxiety and depression-like behavior cannot be explained by a universal and brain wide mechanisms, and therefore the earlier proposed dualistic action of CRFR1 and CRFR2 in stress may not hold. The gene discussed is CRHR2; the disease is depressive disorder.