Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia.
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.
Arion
Dominique
D
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Unger
Travis
T
Lewis
David A
DA
Levitt
Pat
P
Mirnics
Károly
K
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000235:genetics / Q000523:psychology; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016000:Cluster Analysis; D004247:DNA / Q000235:genetics; D003627:Data Interpretation, Statistical; D030541:Databases, Genetic; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007109:Immunity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D009836:Oligodendroglia / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics; D017397:Prefrontal Cortex / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013569:Synapses / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D014150:Antipsychotic Agents; D018832:Molecular Chaperones; D009841:Oligonucleotides; D004247:DNA