The overall phenotype of our female conditional KOs is interesting. The combination of an increase in depression-like behavior but a tendency for reduced responses to anxiogenic stimuli may seem counterintuitive, since some depressed patients show increased anxiety symptoms and depression and anxiety co-occur in some families. However, a few points must be emphasized. First, our results from the anxiety tests in female mice show trends only, and without statistical significance, the findings must be viewed with caution. Second, depression is not a unitary disorder; it is very likely that multiple subtypes exist with distinct etiology and pathophysiology