Integrative network analysis identifies differential regulation of neuroimmune system in Schizophrenia and Bipolar disorder

Abstract

Background: Neuropsychiatric disorders such as Schizophrenia (SCZ) and Bipolar disorder (BPD) pose a broad range of problems with different symptoms mainly characterized by some combination of abnormal thoughts, emotions, behaviour, etc. However, in depth molecular and pathophysiological mechanisms among different neuropsychiatric disorders have not been clearly understood yet. We have used RNA-seq data to investigate unique and overlapping molecular signatures between SCZ and BPD using an integrative network biology approach. Methods: RNA-seq count data were collected from NCBI-GEO database generated on post-mortem brain tissues of controls (n = 24) and patients of BPD (n = 24) and SCZ (n = 24). Differentially expressed genes (DEGs) were identified using the consensus of DESeq2 and edgeR tools and used for downstream analysis. Weighted gene correlation networks were constructed to find non-preserved (NP) modules for SCZ, BPD and control conditions. Topological analysis and functional enrichment analysis were performed on NP modules to identify unique and overlapping expression signatures during SCZ and BPD conditions. Results: We have identified four NP modules from the DEGs of BPD and SCZ. Eleven overlapping genes have been identified between SCZ and BPD networks, and they were found to be highly enriched in inflammatory responses. Among these eleven genes, TNIP2, TNFRSF1A and AC005840.1 had higher sum of connectivity exclusively in BPD network. In addition, we observed that top five genes of NP module from SCZ network were downregulated which may be a key factor for SCZ disorder. Conclusions: Differential activation of the immune system components and pathways may drive the common and unique pathogenesis of the BPD and SCZ.

Keywords

• Bipolar disorder
• Schizophrenia
• Systems biology
• WGCNA
• Inflammatory responses
• Immune responses