Global Expression Studies of Schizophrenic Brain: A Meta-Analysis Study Linking Neurological Immune System with Psychological Disorders.

Abstract

Schizophrenia, a psychological disorder with enormous societal impact, is a result of abnormalities in gene expression and dysregulation of the immune response in the brain. Few studies have been conducted to understand its etiology, however, the exact molecular mechanism largely remains unknown, though some poorly understood theories abound. Present meta-study links the role of central nervous system, immunological system and psychological disorders by using global expression approach and pathway analysis. We retrieved genome-wide mRNA expression data and clinico-pathological information from five independent studies of schizophrenic patients from Gene Expression Omnibus database. We continued further with three studies having common platform. Our result showed a total of 527 differentially expressed genes of which 314 are up regulated and 213 are down regulated. After adjusting the sources of variation, we carried out pathway and gene ontology analysis, and observed alteration of 14-3-3-mediated signaling, γ-aminobutyric acid receptor signaling, role of nuclear factor of activated T-cells in regulation of the immune response, G beta gamma signaling, dopamine- and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000 feedback in cAMP signaling, complement system, axonal guidance signaling, dendritic cell maturation, cAMP response element-binding protein signaling in neurons and interleukin-1 signaling pathways and networks. Conclusively, our global gene expression pathway and gene set enrichment analysis studies suggest disruption of many common pathways and processes, which links schizophrenia to immune and central nervous system. Present meta-study links the role of central nervous system, immunological system and psychological disorders by using global expression approach and pathway analysis.