Altered gene expression in the superior temporal gyrus in schizophrenia

Abstract

Background: The superior temporal gyrus (STG), which encompasses the primary auditory cortex, is believed to be a major anatomical substrate for speech, language and communication. The STG connects to the limbic system (hippocampus and amygdala), the thalamus and neocortical association areas in the prefrontal cortex, all of which have been implicated in schizophrenia.

Results: To identify altered mRNA expression in the superior temporal gyrus (STG) in schizophrenia, oligonucleotide microarrays were used with RNA from postmortem STG tissue from 7 individuals with schizophrenia and 7 matched non-psychiatric controls. Overall, there was a trend towards down-regulation in gene expression, and altered expression of genes involved in neurotransmission, neurodevelopment, and presynaptic function was identified. To confirm altered expression identified by microarray analysis, the mRNA expression levels of four genes, IPLA2gamma, PIK31R1, Lin-7b and ATBF1, were semi-quantitatively measured using relative real-time PCR. A number of genes with altered expression in the STG were also shown to have similar changes in expression as shown in our previous study of peripheral blood lymphocytes in schizophrenia.

Conclusion: This study has identified altered expression of genes in the STG involved in neurotransmission and neurodevelopment, and to a lesser extent presynaptic function, which further support the notion of these functions playing an integral role in the development of schizophrenia.

Figure 1

Average ratio of expression of 19,000 genes in the STG from participants with schizophrenia compared to non-psychiatric controls. The central blue line indicates an expression ratio of 1 (ie: equal expression) and the two outer blue lines indicate a 1.5-fold change. Down-regulation is represented as green, up-regulation as red and normal expression as yellow. 191 genes were up-regulated by more than 1.5 fold and 428 were down-regulated by greater than 1.5 fold. The x-axis shows the average level of fluorescence present on the microarrays for each gene.

Figure 2

SAM plot of gene expression in the STG from participants with schizophrenia compared to non-psychiatric controls. Average expression of 8737 genes expressed in STG tissue from 7 matched pairs of individuals with schizophrenia and non-psychiatric controls. The central blue line indicates equal expression and the two outer blue lines indicate significantly altered expression (Δ = 0.49, FDR = 0.47), genes in red were significantly up-regulated in schizophrenia compared to controls and genes in green were significantly down-regulated in schizophrenia compared to controls. 216 genes were significantly down-regulated and 85 genes were significantly up-regulated.