Tardive dyskinesia is caused by maladaptive synaptic plasticity: A hypothesis

Authors

  • James T. Teo MA, MRCP, PhD,

    Corresponding author
    1. Sobell Department of Motor Neuroscience, University College London Institute of Neurology, London, United Kingdom
    • Sobell Department of Motor Neuroscience, Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom
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  • Mark J. Edwards MRCP, PhD,

    1. Sobell Department of Motor Neuroscience, University College London Institute of Neurology, London, United Kingdom
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  • Kailash Bhatia MD, DM, FRCP

    1. Sobell Department of Motor Neuroscience, University College London Institute of Neurology, London, United Kingdom
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  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

Abstract

It has been 50 years since the first patients with tardive dyskinesia (TD) were described, but the pathophysiology is only partially understood and effective treatments have remained elusive. Newer atypical antipsychotics with less nonspecific activity at dopamine receptors have not heralded the end of tardive dyskinesia and merely highlight the incomplete understanding of the disorder.

We present an overview of the existing pathophysiology of the disorder and incorporate recent developments in genetics and the study of human synaptic plasticity in other hyperkinetic movement disorders. We propose a hypothesis that dopamine-receptor sensitization and altered function of the N-methyl-D-aspartate receptor produces maladaptive synaptic plasticity, which allows the encoding of abnormal motor programs, and propose studies that would falsify or support this hypothesis.

In conclusion, a maladaptive synaptic plasticity” hypothesis goes some way toward filling in the gaps of existing theories of TD with the pathophysiology of other hyperkinetic movement disorders. © 2012 Movement Disorder Society

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