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Glutamatergic Neurotransmission Abnormalities and Schizophrenia

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Handbook of Schizophrenia Spectrum Disorders, Volume I

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Abstract

Schizophrenia affects approximately 1% of the adult population worldwide and requires lifelong therapy. Hyperfunction of the dopaminergic system has long been hypothesized as the underlying cause of schizophrenia. However, this hypothesis explains mostly the positive symptoms associated with schizophrenia. Several lines of evidence point to the glutamatergic system and suggest that abnormalities in this system may play a crucial role in the pathophysiological features of schizophrenia. Most prominently, N-methyl-d-aspartate receptor hypofunction has been associated with the positive, negative, and cognitive symptoms of schizophrenia. In this chapter, we describe the evidence showing that N-methyl-d-aspartate receptor hypofunction may be crucial in the pathophysiological features of this disorder. Although a plethora of evidence is available from preclinical studies, this chapter is focused mainly on the findings from patients with schizophrenia. In addition to N-methyl-d-aspartate receptors, we also describe the findings of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate receptors and glutamate transporters in patients with schizophrenia. Overall, these findings suggest that therapeutic agents directed toward glutamatergic systems may be helpful in the treatment of positive and negative symptoms and cognitive deficits associated with schizophrenia.

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Abbreviations

NMDA:

N-methyl-d-aspartate

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate

PCP:

Phenylcyclidine

GluR:

Glutamate receptor

PSD:

Postsynaptic density

MRS:

Magnetic resonance spectroscopy

NAAAG:

N-acetyl-L-aspartyl-L-glutamate

mGluR:

Metabotropic glutamate receptor

GlyT:

Glycine transporter

GLAT:

Glutamate transporter

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Acknowledgements

This study was supported by the grants from the National Institute of Mental Health (RO1 MH068777, RO1MH082802, and R21081099), National Alliance for Research on Schizophrenia and Depression, and American Foundation for Suicide Prevention to Dr. Dwivedi; and National Institute of Mental Health (RO1 MH48153 and RO1 MH56528) to Dr. Pandey.

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Authors and Affiliations

  1. Department of Psychiatry, University of Illinois, Chicago, IL, USA

    Yogesh Dwivedi & Ghanshyam N. Pandey

Authors
  1. Yogesh Dwivedi
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  2. Ghanshyam N. Pandey
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Correspondence to Yogesh Dwivedi .

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  1. Sha'ar Menashe Mental Health Center, Hadera, 38814, Israel

    Michael S. Ritsner

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© 2011 Springer Science+Business Media B.V.

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Dwivedi, Y., Pandey, G.N. (2011). Glutamatergic Neurotransmission Abnormalities and Schizophrenia. In: Ritsner, M. (eds) Handbook of Schizophrenia Spectrum Disorders, Volume I. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0837-2_13

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