Prefrontal abnormality of schizophrenia revealed by DNA microarray: impact on glial and neurotrophic gene expression.

DNA microarrays with isotope labeling from gene-specific primers enable sensitive detection of rare mRNAs, including neurotrophin and cytokine mRNAs in the brain. Using high-quality RNA from postmortem brains, gene-expression profiles covering 1373 genes were assessed in the dorsoprefrontal cortex of schizophrenic patients and compared with those of nonpsychiatric subjects. Statistical analysis of the DNA microarray data confirmed the findings of a previous GeneChip study by Hakak et al. (Proc. Natl. Acad. Sci. USA Vol. 98, pp. 4746-4751, 2001). The highest frequency of mRNA expression alterations occurred in oligodendrocyte- and astrocyte-related genes in the prefrontal cortex of schizophrenic patients, followed by the category for the genes for growth factors/neurotrophic factors and their receptors. Whether each mRNA signal represents the expression of the individual genes or homologous genes in the category remains to be determined, however. To control for potential medication effects on patients, RNA from cynomolgus monkeys that were treated with haloperidol for 3 months was also subjected to DNA microarray analysis. A few genes overlapped between the gene-expression profiles of the monkeys and patients. The present profiling study suggests a potential biological link between abnormal neurotrophic signals and impaired glial functions in schizophrenic pathology.