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Neurosteroids in Cortical Development and the Etiology of Schizophrenia

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Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders

Schizophrenia is thought to be a neurodevelopmental disorder, and both genetic and non-genetic risk factors associated with the disease are related to neural development and function. However, no one mechanism has yet been proposed that explains the entire pathology of the disorder. One pathway that is clearly involved, however, is signaling via GABA. Post-mortem investigations reveal deficits in GABA transmission and altered localization of some GABAergic interneurons in the brains of schizophrenic patients. Furthermore, GABAergic signaling during early cortical development influences neuronal migration and later enhances synapse formation. Modulators of GABA signaling, including the neuroactive steroids, are therefore critical for normal neurodevelopment. Neurosteroids, including allopregnanolone, are potent, endogenous, stress-responsive modulators of GABAA receptor function. Cortical neurosteroid levels are dynamically regulated across embryonic and early postnatal development, and may differentially affect GABAA receptor function across distinct ontological periods. Furthermore, neuroactive steroid levels are increased in response to gestational stress or infection, both of which are risk factors associated with the development of a schizophrenia-vulnerable phenotype. The unique situation of neurosteroids at the junction of stress and GABA transmission makes them an important mechanism linking stress and neurodevelopmental vulnerability, as in the etiology of schizophrenia.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Charles Drew University of Medicine and Science, Los Angeles, CA, USA

    Samantha S. Gizerian Ph.D

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  1. Samantha S. Gizerian Ph.D
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  1. Sha'ar Menashe Mental Health Center, Hadera, Israel

    Michael S. Ritsner M.D., Ph.D

  2. Geha Mental Health Center, Petah Tikva, Israel

    Abraham Weizman MD

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© 2008 Springer Science + Business Media, B.V

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Gizerian, S.S. (2008). Neurosteroids in Cortical Development and the Etiology of Schizophrenia. In: Ritsner, M.S., Weizman, A. (eds) Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6854-6_15

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  • DOI: https://doi.org/10.1007/978-1-4020-6854-6_15

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-1-4020-6853-9

  • Online ISBN: 978-1-4020-6854-6

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