M101. Different Changes in Cortical Gene Expression in Subjects With Schizophrenia, With and Without Low Muscarinic M1 Receptors, Predict Different Pathways are Involved in the Pathophysiologies of the Two Sub-groups

Abstract

Abstract Background: We tested the hypothesis that changes in gene expression in the dorsolateral prefrontal cortex (DLPFC) from 2 sub-groups of subjects with schizophrenia, one with a marked deficit in muscarinic M1 receptors (MRDS), would identify different biochemical pathways that would be affected by their aetiologies. Methods: We measured levels of mRNA in Brodmann’s area 9 from 15 MRDS, 15 subjects with schizophrenia but without a deficit in muscarinic M1 receptors (non-MRDS) and 15 Controls using Affymetrix Exon 1.0 ST arrays. Results: There were changes in mRNA levels for 65 genes only in the cortex of subjects with MRDS and these changes predicted changes in pathways involved in cellular movement and cell-to-cell signaling. Levels of mRNA for 45 genes were changed non-MRDS and these changes predicted changes in pathways involved in cellular growth and proliferation as well as cellular function and maintenance. At the level of schizophrenia, changes in gene expression predicted effects on pathways involved in amino acid metabolism, molecular transport and small molecule biochemistry in both MRDS and non-MRDS. Conclusion: Our data argues a prominent role for glial function in MRDS and neurodevelopment in non-MRDS. Our study gives new insight into the molecular pathways affected in the cortex of subjects with MRDS and supports the notion that studying sub-groups within the syndrome of schizophrenia is worthwhile.