Implications of adult hippocampal neurogenesis in antidepressant action.
In the dentate gyrus of the hippocampus, cell birth and maturation into neurons, or neurogenesis, occur throughout the lifetime of animals and humans. Multiple factors have been shown to regulate adult neurogenesis, and a number of findings in this field have had a large impact on basic and clinical research in depression. It has been reported that both physical and psychosocial stress paradigms, as well as some animal models of depression, produce a decrease in hippocampal cell proliferation and neurogenesis. Conversely, long-term, but not short-term, treatment with different classes of antidepressant drug increases cell proliferation and neurogenesis. Patients with depressive disorders or post-traumatic stress disorder have reduced hippocampal volume. Given this interaction of stress, depression and neurogenesis, a current hypothesis is that reduced adult hippocampal cell proliferation or neurogenesis may be involved in the pathophysiology of depression and that reversal or prevention of the decrease in neurogenesis may be one way in which the antidepressant drugs exert their effects. Research from this emerging field will further our understanding of the effects of stress and depression on the brain and the mechanism of action of antidepressant drugs.
Malberg
Jessica E
JE
Wyeth Research, Princeton, NJ 08543, USA. malberj1@wyeth.com
D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002465:Cell Movement / Q000502:physiology; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology
D000928:Antidepressive Agents