Effect of valproic acid on behavior and plasma amino acid concentrations in chronic schizophrenic patients

Valproic acid (VPA), or 2-propylpentanoic acid, has an anticonvulsant effect and is used clinically in the treatment of petit mal seizures (Simon and Penry 1975). Although VPA increases brain gamma-aminobutyric acid (GABA) concentrations, the anticonvulsant effect appears to be more closely associated with a reduction in brain concentrations of aspartic acid (Chapman et al. 1982, 1983; Schechter et al. 1978). Based on the inhibitory action of GABA on brain dopamine systems (Waszczak and Waiters 1979), there has recently been considerable interest in the experimental treatment of schizophrenia with GABA agonists or agents that increase brain GABA concentrations. The results of these experiments have generally been equivocal (cf. Garbutt and van Kammen 1983). VPA in particular has been administered to schizophrenic patients in three previous studies. In two of these, patients improved during VPA treatment (Linnoila et al. 1976: Nagao et al. 1979). The third study reported that patients worsened