Molecular Psychiatry
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May 2000, Volume 5, Number 3, Pages 262-269
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Millennium Article
Adult brain neurogenesis and psychiatry: a novel theory of depression
B L Jacobs1, H van Praag2 and F H Gage2

1Program in Neuroscience, Princeton University, Princeton, NJ 08544-1010, USA

2The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037-1099, USA

Correspondence to: B L Jacobs, Program in Neuroscience, Princeton University, Princeton, NJ 08544-1010, USA. E-mail:


Neurogenesis (the birth of new neurons) continues postnatally and into adulthood in the brains of many animal species, including humans. This is particularly prominent in the dentate gyrus of the hippocampal formation. One of the factors that potently suppresses adult neurogenesis is stress, probably due to increased glucocorticoid release. Complementing this, we have recently found that increasing brain levels of serotonin enhance the basal rate of dentate gyrus neurogenesis. These and other data have led us to propose the following theory regarding clinical depression. Stress-induced decreases in dentate gyrus neurogenesis are an important causal factor in precipitating episodes of depression. Reciprocally, therapeutic interventions for depression that increase serotonergic neurotransmission act at least in part by augmenting dentate gyrus neurogenesis and thereby promoting recovery from depression. Thus, we hypothesize that the waning and waxing of neurogenesis in the hippocampal formation are important causal factors, respectively, in the precipitation of, and recovery from, episodes of clinical depression. Molecular Psychiatry(2000) 5, 262-269.


rat; mouse; dentate gyrus; serotonin; hippocampus; stress; 5-HT1A; glucocorticoids; epilepsy

Received 8 October 1999; revised 8 November 1999; accepted 8 November 1999
May 2000, Volume 5, Number 3, Pages 262-269
Table of contents    Previous  Abstract  Next   Full text  PDF