title: Brain gamma-aminobutyric acid abnormality in tardive dyskinesia. Reduction in cerebrospinal fluid GABA levels and therapeutic response to GABA agonist treatment.
abstract: A double-blind, placebo-controlled trial of gamma-vinyl gamma-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 gamma-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 compliment a growing body of experimental evidence suggesting a critical role for GABA-ergic neurons in the pathophysiology of tardive dyskinesia.
mesh_terms: D000328:Adult; D000614:Aminocaproates / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000134:cerebrospinal fluid / Q000378:metabolism; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000502:physiology*
chemical_list: D000614:Aminocaproates; D007555:Isoxazoles; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin; C015542:gaboxadol