Molecular Evidence for Increased Expression of Genes Related to Immune and Chaperone Function in the Prefrontal Cortex in Schizophrenia

Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Biological Psychiatry (Impact Factor: 10.26). 10/2007; 62(7):711-21. DOI: 10.1016/j.biopsych.2006.12.021
Source: PubMed


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.
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.
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.
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.

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    • "However, their relation to the structural changes is not clear. These studies have repeatedly shown altered expression of immune-related markers in prefrontal (Arion et al., 2007; Saetre et al., 2007; Martins-de-Souza et al., 2009; Fillman et al., 2013) and temporal (Wu et al., 2012) cortices as well as in the hippocampus (Hwang et al., 2013) of schizophrenia patients. "
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    • "Longitudinal studies in animal models further indicate that infection-induced developmental neuroinflammation may be pathologically relevant beyond the antenatal and neonatal periods, and may contribute to progression of disease, associated with gradual development of full-blown schizophrenia.27 Arion et al carried out a DNA microarray study that showed increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia.28 Narayan et al profiled genome-wide expression patterns in the prefrontal cortex in subjects with schizophrenia at different stages of the illness. "
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    • "We did not replicate the previous report of increased HSPA1A, HSPA1B and HSPB1 expression in the DLPFC found in 14 patients with schizophrenia relative to controls34. This may be due to the large variance in mRNA observed for these transcripts perhaps due to increased biological heterogeneity observed in schizophrenia, or differences in the sensitivities and target specificities of microarray, RNA-Seq and qPCR methods. "
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