Abstract

Schizophrenia is a heterogeneous spectrum disorder of unknown etiology that is going to be a public concern around the world. The molecular association between the pathophysiology of schizophrenia (SP) and bipolar disorder (BD) is still not clear enough. To address this gap, we developed an integrated bioinformatics approach to identify common molecular signatures and possible interactive pathways that are common in the molecular pathogenic process between SP and BD. We employed pluripotent stem cell (iPSC)-derived cortical interneuron transcriptomic data and post-mortem brain transcriptomic data from patients with SP and BD, respectively. Twenty common differentially expressed genes (DEGs) were identified between SP and BD. Positive regulation of cyclic AMP (cAMP)-mediated signaling and regulation of the metabolic process were found to be common biological pathways between these two disorders. Protein-protein interactions and transcriptional regulatory interactions identified with hub-bottleneck proteins (LY6G5B, DLGAP2, DXO, EGR3, BAG6, DL-GAP2, SKIV2L, CSNK2B and RXRB), regulatory transcription factors (FOXC1, GATA2, RELA and ELK4), and regulatory microRNAs (hsa-mir-34a-5p, hsa-mir23b-3p, hsa-mir-146a-5p, hsa-mir-27a-3p, and hsa-mir-1-3p) are as key molecular signatures between SP and BD. Protein-chemical and protein-drug interactions revealed valproic acid, antirheumatic agents, trichostatin A, aarsenic, and 4-(5-benzo (1,3) dioxol-5-yl-4-pyridin-2yl-1H-imidazole-2-yl) benzamide and isopropyl alcohol compounds could be used as a potential therapeutic target molecule against SP and BD. The research findings would be used in wet lab-based research to further clarify potential therapeutic targets for the treatment of SP and BP disorders.