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. 2001 Apr 10;98(8):4746-51.
doi: 10.1073/pnas.081071198.

Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia

Y Hakak  1 , J R Walker, C Li, W H Wong, K L Davis, J D Buxbaum, V Haroutunian, A A Fienberg
Affiliations

Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia

Y Hakak et al. Proc Natl Acad Sci U S A. .

Abstract

Neuropathological and brain imaging studies suggest that schizophrenia may result from neurodevelopmental defects. Cytoarchitectural studies indicate cellular abnormalities suggestive of a disruption in neuronal connectivity in schizophrenia, particularly in the dorsolateral prefrontal cortex. Yet, the molecular mechanisms underlying these findings remain unclear. To identify molecular substrates associated with schizophrenia, DNA microarray analysis was used to assay gene expression levels in postmortem dorsolateral prefrontal cortex of schizophrenic and control patients. Genes determined to have altered expression levels in schizophrenics relative to controls are involved in a number of biological processes, including synaptic plasticity, neuronal development, neurotransmission, and signal transduction. Most notable was the differential expression of myelination-related genes suggesting a disruption in oligodendrocyte function in schizophrenia.

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Figures

Figure 1
Figure 1
Relative expression levels of the 89 genes differentially expressed in schizophrenic samples relative to control samples. Each column displays the gene expression levels in individual samples and each row corresponds to the individual genes. The expression values for each gene are normalized to have a mean of 0 and a standard deviation of 1. Expression levels are color coded relative to the mean: blue for values less than the mean, red for values greater than the mean. The dendrogram on the left illustrates the final clustering tree resulting from hierarchical clustering of gene expression values. The branch lengths of the tree reflect the degree of similarity of gene expression values across the 24 samples.
Figure 2
Figure 2
Linear discriminant analysis of schizophrenic and control samples. LDA was applied to the data matrix of the 24 samples by (A) the 89 gene set, (B) the six myelination-related gene set, and (C) the 35 myelination-related gene set. Linear discriminants were determined for each sample and plotted. C = control, S = schizophrenic. Control samples are coded in black and schizophrenic samples in red. Sample identities correspond to those in Fig. 1.
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