Brain γ-aminobutyric acid abnormality in tardive dyskinesia: Reduction in cerebrospinal fluid GABA levels and therapeutic response to GABA agonist treatment

G. K. Thaker, C. A. Tamminga, L. D. Alphs, J. Lafferman, T. N. Ferraro, T. A. Hare

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A double-blind, placebo-controlled trial of γ-vinyl γ-aminobutyric acid (GVG) and 4,5,6,7-tetrahydroisoxazolo-(5,4-c)pyridine-3-ol (THIP) was carried out in drug-free schizophrenic patients with tardive dyskinesia. A significant decrease in dyskinetic symptoms occurred with the administration of GVG, associated with a twofold increase in cerebrospinal fluid levels of GABA; THIP produced a more moderate, yet consistent decrease in the involuntary movements. A pathophysiologic role for γ-aminobutyric acid (GABA)-mediated neuronal transmission in tardive dyskinesia was explored by analyzing cerebrospinal fluid GABA concentrations in drug-free schizophrenic patients with and without tardive dyskinesia. A significant reduction in cerebrospinal fluid levels of GABA was observed in the dyskinetic schizophrenics compared with the nondyskinetic controls. These data complement a growing body of experimental evidence suggesting a critical role for GABA-ergic neurons in the pathophysiology of tardive dyskinesia.

Original languageEnglish (US)
Pages (from-to)522-529
Number of pages8
JournalArchives of General Psychiatry
Issue number6
Publication statusPublished - 1987


ASJC Scopus subject areas

  • Psychiatry and Mental health

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