Title:Global Expression Studies of Schizophrenic Brain: A Meta-Analysis Study Linking Neurological Immune System with Psychological Disorders
Volume: 15
Issue: 4
Author(s): Sajjad Karim, Mohammad A. Kamal, Zafar Iqbal, Shakeel A. Ansari, Mahmood Rasool, Mohammed H. Al-Qahtani, Gazi Damanhouri and Zeenat Mirza
Affiliation:
Keywords:
Schizophrenia, psychological disorder, gene expression, immune system, DNA microarray, central nervous system.
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.
