title: Tardive dyskinesia is caused by maladaptive synaptic plasticity: a hypothesis.
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.
authors.affiliation: Sobell Department of Motor Neuroscience, University College London Institute of Neurology, London, United Kingdom. jthteo@gmail.com
authors.forename: James T
authors.initials: JT
authors.lastname: Teo
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: Kailash
authors.initials: K
authors.lastname: Bhatia
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D014150:Antipsychotic Agents / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D018683:Excitatory Amino Acid Agents / Q000633:toxicity; D006801:Humans; D009069:Movement Disorders / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D016202:N-Methylaspartate / Q000378:metabolism / Q000633:toxicity; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D018683:Excitatory Amino Acid Agents; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate