Variations in myelin and oligodendrocyte-related gene expression across multiple brain regions in schizophrenia: a gene ontology study.

Large-scale gene expression studies in schizophrenia (SZ) have generally focused on the dorsolateral prefrontal cortex. Studies of other brain regions have been less frequent and have rarely been performed in the same subjects. We analyzed postmortem gene expression in multiple cortical regions (Brodmann areas 8, 10, 44, 46, 23/31, 24/32, 20, 21, 22, 36/28, 7 and 17, respectively) as well as in the hippocampus, caudate nucleus, and putamen of 13 SZ and 13 control subjects using Affymetrix GeneChip(R) microarrays. The superior temporal cortex (BA22) and cingulate cortices (BA24/32, 23/31) of subjects with SZ demonstrated more profound alterations of gene expression than other brain regions compared to controls [Katsel, P., Davis, K.L., Gorman, J.M., Haroutunian, V., in press. Variations in differential gene expression patterns across multiple brain regions in schizophrenia. Schizophr. Res.]. Functional categorization of genes whose expression was altered revealed multiple gene ontology classes that included oligodendrocyte/myelin-related genes. These myelin-related ontologies were among the top scored categories in temporal and cingulate gyri and in the hippocampus relative to other brain regions. The most altered transcripts in SZ were those encoding for proteins involved in determination of glial differentiation, myelin structure and adhesion proteins participating in axoglial contacts. Hierarchical clustering demonstrated that these myelin-related gene expression abnormalities in SZ were most pronounced in the hippocampus, superior temporal and cingulate cortices. The high representation of abnormally expressed oligodendrocyte/myelin genes in brain regions with the largest numbers of abnormally expressed genes in SZ confirmed their involvement in the disease process and suggested that the integrity of axon-myelin interaction may be impaired in SZ.