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

Dominique Arion, Travis Unger, David A. Lewis, Pat Levitt, Károly Mirnics

Research output: Contribution to journalArticle

239 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)711-721
Number of pages11
JournalBiological Psychiatry
Volume62
Issue number7
DOIs
StatePublished - Oct 1 2007

Keywords

  • DNA
  • heat-shock protein
  • immune system
  • microarray
  • postmortem brain
  • prefrontal cortex
  • qPCR
  • schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry

Fingerprint Dive into the research topics of 'Molecular Evidence for Increased Expression of Genes Related to Immune and Chaperone Function in the Prefrontal Cortex in Schizophrenia'. Together they form a unique fingerprint.

  • Cite this