Mitra Farahmandnejad - Department of Pharmacology & Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Seyed Mahdi Sadati - Department of Pharmacology & Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran- Department of Neuroscience, School of Sciences and Advanced Technology in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Pouria Mosaddeghi - Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Amirhossein Sakhteman - Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran- Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
Negar Firouzabadi - Department of Pharmacology & Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

Major depressive disorder is a long-term relapsing condition associated with high levels of disability,mortality and reduce the quality of life. According to the World Health Organization, about ۳۵۰ millionpeople in the world are affected by this condition. An estimated ۵۰% of depressed patients are inadequatelytreated by available interventions. Therefore, the purpose of this study was to systematically investigate andreconstruct the genetic network of major depressive disorder (MDD) for finding most important genes andbiological pathways to assay with experimental condition in next studies and finally hypothesize newtreatment.In this study, through an extensive review of existing published studies and popular databases, all genesassociated with MDD were found. Then, in order to integrate the results, all the interactions between thesegenes were explored and the achievement was represented as an interactive genetic network withGeneMANIA and other plugins. Furthermore, the reconstructed network was analyzed with Cytoscape. Afterfinding most important genes, we found most important pathways with Gene Ontology (GO) and Reactomedatabases. Finally, we investigated diseases with the most number of shared genes with MDD by DisGeNET.It was found that GRIN۲A, APP, JUN, PPP۳CA and EGFR are the most central nodes in the genetic networkof MDD. Functional and pathway enrichment analysis showed that GPCR signaling, cytokine and immunesystem signaling are the main systems in patients with MDD. By studying genes shared between MDD andother diseases, it was cleared that MDD, Schizophrenia, Alzheimer’s disease and some types of cancer havethe most number of shared genes.The results of this study, in addition to reviewing the available results as a comprehensive and integratedmanner, provide new hypotheses for future studies. It shows that we must use systems biology approach tomanage and treat disorders. These outcomes must be done in experimental study.

Major depressive disorder, Systems biology, Cytoscape, Genetic network, pathway