Measurement of GABAergic parameters in the prefrontal cortex in schizophrenia: Focus on GABA content, GABA(A) receptor alpha-1 subunit messenger RNA and human GABA transporter-1 (HGAT-1) messenger RNA expression

The hypothesis that the pathophysiology of schizophrenia may be associated with a dysfunction in GABA transmission in the human prefrontal cortex was investigated. Human post mortem brain tissue from 10 control cases and six cases of schizophrenia were processed for amino acid analysis and for radio active in situ hybridization. Laminae III and V of three prefrontal cortica l areas were examined in detail, namely Brodmann areas 9, 10 and 11. Of the se three areas significant changes in GABAergic markers were found only in areas 9 and 10. Of note, a significant decrease in the tissue content of GA BA was observed and this was accompanied by a marked increase in the cellul ar expression of the GABA(A) receptor alpha-1 subunit messenger RNA and a m arked decrease in the expression of human GABA transporter-1, the messenger RNA encoding the neuronal GABA transporter protein. The amino acid analysis data provided in this study coupled with the detail ed cellular study of several GABAergic markers in the human prefrontal cort ex provide direct evidence in support of a disturbance in GABA transmission in the prefrontal cortex, which may be loosely termed "hypofrontality". (C ) 1999 IBRO. Published by Elsevier Science Ltd.