GABA agonist-induced changes in motor, oculomotor, and attention measures correlate in schizophrenics with tardive dyskinesia.
Saccadic distractibility, Stroop color-word scores, and serial dyskinesia assessments were obtained on 10 schizophrenic patients with tardive dyskinesia during a pharmacologic challenge with placebo or 7 mg muscimol, a potent, direct-acting GABA agonist. Although no significant difference in the measures was evident between conditions, a significant correlation was found between GABA agonist-induced changes in saccadic distractibility and dyskinesia scores where no correlation existed between these measures on placebo. Improvement in saccadic distractibility was also correlated with reduction in attention performance, as measured by Stroop. These effects are not due to sedation. The correlation between dyskinesia and saccadic distractibility is consistent with a model of parallel motor and oculomotor cortico-striatal-thalamic circuits in humans. This work supports the hypothesis that a dysfunction in GABA-mediated neurotransmission may be the basis for tardive dyskinesia.
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228.
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Cassady
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Thaker
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Moran
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Birt
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Tamminga
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D002908:Chronic Disease; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D004525:Efferent Pathways / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006801:Humans; D008032:Limbic System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009118:Muscimol / Q000494:pharmacology*; D009460:Neurologic Examination / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D012438:Saccades / Q000187:drug effects* / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology; D013787:Thalamic Nuclei / Q000187:drug effects / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D014150:Antipsychotic Agents; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid