Depression, Antidepressants, and Neurogenesis: A Critical Reappraisal
Neuropsychopharmacology (2011) 36, 2589–2602
The neurogenesis hypothesis of depression posits (1) that neurogenesis in the subgranular zone of the dentate gyrus is regulated negatively by stressful experiences and positively by treatment with antidepressant drugs and (2) that alterations in the rate of neurogenesis play a fundamental role in the pathology and treatment of major depression. This hypothesis is supported by important experimental observations, but is challenged by equally compelling contradictory reports. This review summarizes the phenomenon of adult hippocampal neurogenesis, the initial and continued evidence leading to the development of the neurogenesis hypothesis of depression, and the recent studies that have disputed and/or qualified those findings, to conclude that it can be affected by stress and antidepressants under certain conditions, but that these effects do not appear in all cases of psychological stress, depression, and antidepressant treatment.
Keywords: neurogenesis; dentate gyrus; neurotrophic factors; stress; depression; antidepressant
Screening: Your brain on drugs Nature Chemical Biology 6, 639–640 (2010) http://www.nature.com/nchembio/journal/v6/n9/full/nchembio.427.html Manipulation of stem cells is an important therapeutic goal that has proven difficult to achieve. A recent report describes a novel in vivo small-molecule screen and identifies a modulator of mammalian neurogenesis that partially reverses age-related declines in cognition. Treatment with P7C3 was found to promote mitochondrial integrity under normally apoptotic conditions (top). In a rat model of aging, P7C3 promoted survival of newborn neurons (middle) and was associated with enhanced function in the Morris water maze test of learning and memory (bottom).
adult neurogenesis during stress