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Dopaminergic mechanisms and cognitive deficit in schizophrenia

A neurobiological model

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Abstract

A hypothesis is briefly discussed proposing that schizophrenic symptoms are due to a breakdown in a mechanism by which conscious attention is limited and directed. It is shown that this mechanism can be modelled in terms of a simple nerve network in which every channel inhibits all the others. Failure of this inhibition would cause the defect hypothesised to occur in schizophrenia.

It is shown that if dopamine is given a central role as transmitter in such a network then the various predictions about the biochemistry of schizophrenia that follow are not only consistent with the evidence for the ‘dopamine theory’ of schizophrenia, but also with much of the evidence held to be contrary to that theory.

While not purporting to be an experimentally validated description of schizophrenia, this model goes beyond the single amine theories of schizophrenia and links dysfunctions in amine systems with specific behavioural control mechanisms. Given the current state of knowledge, such models can make only limited predictions about the biochemistry of schizophrenia. However, an attempt to link behavioural and biochemical systems in this way will be crucial for the development of viable animal models of schizophrenia.

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Authors and Affiliations

  1. Division of Psychiatry, MRC Clinical Research Centre, Watford Road, HA1 3UJ, Harrow, Middlesex, UK

    Michael H. Joseph, Christopher D. Frith & John L. Waddington

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  1. Michael H. Joseph
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  2. Christopher D. Frith
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  3. John L. Waddington
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Joseph, M.H., Frith, C.D. & Waddington, J.L. Dopaminergic mechanisms and cognitive deficit in schizophrenia. Psychopharmacology 63, 273–280 (1979). https://doi.org/10.1007/BF00433561

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