Neurogenesis and depression: what animal models tell us about the link.

There is growing evidence that stress causes a decrease of neurogenesis in the dentate gyrus and antidepressant treatment in turn stimulates the cell proliferation in the dentate gyrus. This has led to the hypothesis that a decreased neurogenesis might be linked to the pathophysiology of major depression. The article reviews the relationship of depressive-like behavior and neurogenesis in three animal models of depression with high validity: learned helplessness, chronic mild stress and chronic psychosocial stress of the tree shrew. All animal models provide evidence that stress which can lead to depressive-like behavior, in parallel causes a decrease of neurogenesis; vice versa, antidepressant treatment is able to revert not only behavioral changes but also to normalize neurogenesis. But the animal models argue against the notion that decreases of neurogenesis are the cause or the consequence of depressive-like behavior since depressive-like behavior can occur without impairments in neurogenesis and decreasing neurogenesis does not neccessarily lead to depressive-like behavior. This suggests that neurogenesis does not directly control affect but is tightly connected to the modulation of affect by stress and antidepressant measures.