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S002-2

Small RNA Biomarkers of Schizophrenia

Murray J. Cairns

School of Biomedical Sciences & Pharmacy Hunter Medical Research Institute University of Newcastle Callaghan
NSW, Australia, Australia

Background/Objective: Small non-coding microRNA (miRNA) play a significant role as the
specificity factors or guide strands in post-transcriptional gene silencing. These molecules are
enriched in the brain and are emerging as key regulators of brain development and neural function.
Several miRNA genes, in particular MIR137, have also been shown to be genetically associated with
schizophrenia and many of these molecules display changes in cortical expression in postmortem
brain tissue.

Method: While these changes have the potential for significant influence in the central nervous
system, it is plausible that schizophrenia-associated miRNA expression patterns also exist in
non-neural tissue and biological fluids. These signatures may provide the basis of an accessible
biomarker in living subjects that provide clinically significant diagnostic and prognostic information.

Result: To this end we investigated miRNA expression in peripheral blood mononuclear cells
(PBMCs) in patients with schizophrenia and a non-psychiatric comparison group using a commercial
microarray platform. This analysis identified more than 80 differentially expressed molecules with an
FDR<5%. The expression signature was surprisingly enriched with brain-associated miRNA
predicted to be involved in neural and immune system function. Further analysis of cognitive
subtypes within this cohort; suggest there are also patterns of expression, which are predictive of
cognitive deficit in schizophrenia.

Conclusion: We believe that these molecules and their disease-associated expression signatures
could have application in the personalised genomics of schizophrenia as clinically significant
biomarkers for schizophrenia and related sub-phenotypes.