Dataset Information

Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia.

ABSTRACT:

Background

Schizophrenia is characterized by complex gene expression changes. The transcriptome alterations in the prefrontal cortex have been the subject of several recent postmortem studies that yielded both convergent and divergent findings.

Methods

To increase measurement precision, we used a custom-designed DNA microarray platform with long oligonucleotides and multiple probes with replicates. The platform was designed to assess the expression of > 1800 genes specifically chosen because of their hypothesized roles in the pathophysiology of schizophrenia. The gene expression differences in dorsolateral prefrontal cortex samples from 14 matched pairs of schizophrenia and control subjects were analyzed with two technical replicates and four data mining approaches.

Results

In addition to replicating many expression changes in synaptic, oligodendrocyte, and signal transduction genes, we uncovered and validated a robust immune/chaperone transcript upregulation in the schizophrenia samples.

Conclusions

We speculate that the overexpression of SERPINA3, IFITM1, IFITM2, IFITM3, CHI3L1, MT2A, CD14, HSPB1, HSPA1B, and HSPA1A in schizophrenia subjects represents a long-lasting and correlated signature of an early environmental insult during development that actively contributes to the pathophysiology of prefrontal dysfunction.

SUBMITTER: Arion D

PROVIDER: S-EPMC2080683 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Publications

Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia.

Arion Dominique D Unger Travis T Lewis David A DA Levitt Pat P Mirnics Károly K

Biological psychiatry 20070613 7

<h4>Background</h4>Schizophrenia is characterized by complex gene expression changes. The transcriptome alterations in the prefrontal cortex have been the subject of several recent postmortem studies that yielded both convergent and divergent findings.<h4>Methods</h4>To increase measurement precision, we used a custom-designed DNA microarray platform with long oligonucleotides and multiple probes with replicates. The platform was designed to assess the expression of > 1800 genes specifically cho ...[more]

PMID: 17568569

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Project description:BACKGROUND: Schizophrenia, a severe psychiatric disorder, has a lifetime prevalence of 1%. The exact mechanisms underlying this disorder remain unknown, though theories abound. Recent studies suggest that particular cell types and biological processes in the schizophrenic cortex have a pseudo-immature status in which the molecular properties partially resemble those in the normal immature brain. However, genome-wide gene expression patterns in the brains of patients with schizophrenia and those of normal infants have not been directly compared. Here, we show that the gene expression patterns in the schizophrenic prefrontal cortex (PFC) resemble those in the juvenile PFC. RESULTS: We conducted a gene expression meta-analysis in which, using microarray data derived from different studies, altered expression patterns in the dorsolateral PFC (DLFC) of patients with schizophrenia were compared with those in the DLFC of developing normal human brains, revealing a striking similarity. The results were replicated in a second DLFC data set and a medial PFC (MFC) data set. We also found that about half of the genes representing the transcriptomic immaturity of the schizophrenic PFC were developmentally regulated in fast-spiking interneurons, astrocytes, and oligodendrocytes. Furthermore, to test whether medications, which often confound the results of postmortem analyses, affect on the juvenile-like gene expressions in the schizophrenic PFC, we compared the gene expression patterns showing transcriptomic immaturity in the schizophrenic PFC with those in the PFC of rodents treated with antipsychotic drugs. The results showed no apparent similarities between the two conditions, suggesting that the juvenile-like gene expression patterns observed in the schizophrenic PFC could not be accounted for by medication effects. Moreover, the developing human PFC showed a gene expression pattern similar to that of the PFC of naive Schnurri-2 knockout mice, an animal model of schizophrenia with good face and construct validity. This result also supports the idea that the transcriptomic immaturity of the schizophrenic PFC is not due to medication effects. CONCLUSIONS: Collectively, our results provide evidence that pseudo-immaturity of the PFC resembling juvenile PFC may be an endophenotype of schizophrenia.

Dataset Information

Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia.

Background

Methods

Results

Conclusions

Publications

Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia.

Similar Datasets

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