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Adult brain neurogenesis and psychiatry: a novel theory of depression

Abstract

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.

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Acknowledgements

This work was supported by Princeton University and a grant from the NIMH (BLJ). We would also like to thank S Forbes, L Moore, B Miller and L Kitabayashi for their excellent technical assistance. Our special thanks to ML Gage for critical reading of this manuscript. We are grateful for continued support of the Hollfelder Foundation, Robert J and Claire Pasarow Foundation, and a grant and contract from the National Institutes of Health (HV and FHG).

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Correspondence to B L Jacobs.

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Jacobs, B., van Praag, H. & Gage, F. Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry 5, 262–269 (2000). https://doi.org/10.1038/sj.mp.4000712

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