All schizophrenics in this study had been exposed to neuroleptic drugs for decades. The history of neuroleptic exposure for each subject was assessed in detail by examination of his or her medical charts. Of the 26 schizophrenics, 13 had been exposed to neuroleptics within 1 week of death, while neuroleptic medications had been discontinued for the remaining 13 subjects from 1 week prior to death to as long as 124 weeks prior to death. To assess the possible influence of acute neuroleptic exposure on GAD67 gene expression, the schizophrenic group was subdivided into those who had been exposed to neuroleptics within 6 weeks of death (n = 16) vs. those who had been neuroleptic free for more than 6 weeks (n = 9). Comparison of GAD67 gene expression in the dorsolateral prefrontal cortex of these 2 groups of schizophrenics did not reveal any significant differences between the 2 groups (p > 0.4, data not shown). Matching of subjects for age and PMI and the examination of possible neuroleptic influences suggest that the detected abnormality was independent of obvious artifacts.
These results indicate that mRNA regulation of GAD67 is significantly changed in the dorsolateral prefrontal cortex of elderly chronically ill schizophrenics.
Bunney WE and Bunney BG, Evidence for a compromised dorsolateral prefrontal cortical parallel circuit in schizophrenia, Brain Res Rev 31, 138146 (2000)
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