GABA agonist-induced changes in motor, oculomotor, and attention measures correlate in schizophrenics with tardive dyskinesia

Abstract

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.