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The Dopamine Dysfunction in Schizophrenia Revisited: New Insights into Topography and Course

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Current Antipsychotics

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 212))

Abstract

Schizophrenia has long been associated with an imbalance in dopamine (DA) neurotransmission, and brain imaging has played an important role in advancing our knowledge and providing evidence for the dopaminergic abnormalities. This chapter reviews the evidence for DA dysfunction in different brain regions in schizophrenia, in particular striatal, extrastriatal, and prefrontal regions, with emphasis on recently published findings. As opposed to the traditional view that most striatal dopaminergic excess, associated with the positive symptoms of schizophrenia, involves the dopaminergic mesolimbic pathway, recent evidence points to the nigrostriatal pathway as the area of highest dysregulation. Furthermore, evidence from translational research suggests that dopaminergic excess may be present in the prodromal phase, and may by itself, as suggested by the phenotype observed in transgenic mice with developmental overexpression of dorso-striatal D2 receptors, be an early pathogenic condition, leading to irreversible cortical dysfunction.

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Authors and Affiliations

  1. Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University Medical Center, Maastricht, The Netherlands

    Rebecca Kuepper

  2. Department of Psychiatry, Columbia College of Physicians and Surgeons, New York State Psychiatric Institute, Columbia University, 1051 Riverside Drive, New York, 10032, NY, USA

    Mette Skinbjerg & Anissa Abi-Dargham

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  1. Rebecca Kuepper
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  2. Mette Skinbjerg
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  3. Anissa Abi-Dargham
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Correspondence to Anissa Abi-Dargham .

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  1. Institut für Pharmakologie, Universität, Neuroscience Research, Abbott GmbH & Co. KG, Knollstraße, Ludwigshafen, 67061, Germany

    Gerhard Gross

  2. Dept. Psychiatry, University of California San Diego, Gilman Drive 9500, La Jolla, 92093-0804, California, USA

    Mark A. Geyer

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Kuepper, R., Skinbjerg, M., Abi-Dargham, A. (2012). The Dopamine Dysfunction in Schizophrenia Revisited: New Insights into Topography and Course. In: Gross, G., Geyer, M. (eds) Current Antipsychotics. Handbook of Experimental Pharmacology, vol 212. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25761-2_1

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