| Schizophrenia is characterized by complex gene expression
changes. The transcriptome alterations in the prefrontal cortex have been
the subject of several recent postmortem studies which 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 >1,800
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 using 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 (panel). We speculate
that the over-expression 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. |
