The severity of mental disorders is linked to interaction among candidate genes

There is a considerable overlap in the manifestation of symptoms in three mental disorders namely unipolar disorder, bipolar disorder and schizophrenia. A gene coexpression network was developed based on a mutual information approach including four candidate genes (NRG1, DISC1, BDNF and COMT) along with other coexpressing genes in unipolar disorder, bipolar disorder and schizophrenia. There is a significant difference in the degree distribution of nodes between normal and bipolar disorder network and bipolar disorder network and schizophrenia network. Moreover, there is a differential direct connectivity among candidate genes in various mental disorders and between normal and mental disorders. All candidate genes are directly connected to each other in schizophrenia except one pair (NRG1-BDNF) indicating a strong role of inter-gene interactions in the manifestation of severe symptoms in this disease. DISC1 and NRG1 are key hub genes in the unipolar disorder network and the bipolar disorder network but have lost the role of hub genes in schizophrenia network, despite their significant association with schizophrenia. This study indicates that the three psychiatric diseases may not have discrete classes but three phenotypic manifestations of the same continuous disease based on severity.