Adult hippocampal neurogenesis in depression: behavioral implications and regulation by the stress system

Adult hippocampal neurogenesis, the birth of new neurons in the dentate gyrus of the adult brain, can be regulated by stress and antidepressant treatment, and has consistently been implicated in the behavioral neurobiology of stress-related disorders, especially depression and anxiety. A reciprocal relationship between hippocampal neurogenesis and the hypothalamus-pituitary-adrenal (HPA) axis has recently been suggested, which may play a crucial role in the development and in the resolution of depressive symptoms. This chapter will review some of the existing evidence for stress- and antidepressant-induced changes in adult hippocampal neurogenesis, and critically evaluate the behavioral effects of these changes for depression and anxiety. The potential role of neurogenesis as a neurobiological mechanism for sustained remission from depressive symptoms will be discussed, integrating existing data from clinical studies, animal work, and cellular models. The effect of glucocorticoid hormones and the glucocorticoid receptor (GR) will thereby be evaluated as a central mechanism by which stress and antidepressant may exert their opposing effects on neurogenesis, and ultimately, on mood and behavior.