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Re-evaluating the link between neuropsychiatric disorders and dysregulated adult neurogenesis

Nature Medicine volume 22, pages 1239–1247 (2016)Cite this article

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Abstract

People diagnosed with neuropsychiatric disorders such as depression, anxiety, addiction or schizophrenia often have dysregulated memory, mood, pattern separation and/or reward processing. These symptoms are indicative of a disrupted function of the dentate gyrus (DG) subregion of the brain, and they improve with treatment and remission. The dysfunction of the DG is accompanied by structural maladaptations, including dysregulation of adult-generated neurons. An increasing number of studies using modern inducible approaches to manipulate new neurons show that the behavioral symptoms in animal models of neuropsychiatric disorders can be produced or exacerbated by the inhibition of DG neurogenesis. Thus, here we posit that the connection between neuropsychiatric disorders and dysregulated DG neurogenesis is beyond correlation or epiphenomenon, and that the regulation of adult-generated DG neurogenesis merits continued and focused attention in the ongoing effort to develop novel treatments for neuropsychiatric disorders.

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Figure 1: Neurogenesis in the DG and its sensitivity to neurotransmitter systems with relevance to common therapies.
Figure 2: Proven and proposed approaches to targeting new DG neurons to recalibrate DG functional output in neuropsychiatric disorders.

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Acknowledgements

This work was supported by grants to A.J.E. from the US National Institutes of Health (DA023701, DA023555, MH107945) and the US National Aeronautics and Space Administration (NNX15AE09G). S.Y. was funded by a postdoctoral institutional training grant (NIMH T32-MH076690, Basic Science Training Program in the Neurobiology of Mental Illness, PI, C. Tamminga).

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Authors and Affiliations

  1. Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Sanghee Yun, Ryan P Reynolds & Amelia J Eisch

  2. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Irene Masiulis & Amelia J Eisch

  3. Department of Neuroscience and Mahoney Institute of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Amelia J Eisch

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  1. Sanghee Yun
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Correspondence to Amelia J Eisch.

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Causative studies: inducible primary or direct change in dentate gyrus (DG) neurogenesis or DG activity as they relate to DG functional output relevant to psychiatric disorders. (PDF 561 kb)

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Yun, S., Reynolds, R., Masiulis, I. et al. Re-evaluating the link between neuropsychiatric disorders and dysregulated adult neurogenesis. Nat Med 22, 1239–1247 (2016). https://doi.org/10.1038/nm.4218

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