[Skip to Navigation]
June 1987

Brain γ-Aminobutyric Acid Abnormality in Tardive Dyskinesia: Reduction in Cerebrospinal Fluid GABA Levels and Therapeutic Response to GABA Agonist Treatment

Author Affiliations

From the Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland, Baltimore (Drs Thaker, Tamminga, Alphs, and Lafferman); and the Departments of Neurology (Dr Ferraro) and Pharmacology (Dr Hare), Thomas Jefferson University, Philadelphia.

Arch Gen Psychiatry. 1987;44(6):522-529. doi:10.1001/archpsyc.1987.01800180032006

• 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 drugfree 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 compliment a growing body of experimental evidence suggesting a critical role for GABA-ergic neurons in the pathophysiology of tardive dyskinesia.