Seminars

Schizophrenia, bipolar disorder and major depression are complex and devastating mental disorders, each with distinct yet overlapping epidemiologic characteristics such as psychosis. Several single nucleotide polymorphisms (SNPs) and mutations were found to be associated with one or more of the three diseases.
Microarray and proteomics data of post-mortem brain samples also revealed genes which expressed abnormally in these diseases. Nevertheless, there were limited studies on the interrelationships among the genes and encoded proteins associated with schizophrenia, bipolar disorders and major depression. To understand the network biology of mental disorders, protein-protein interaction (PPI) sub-networks for schizophrenia, bipolar disorder and major depression subjects were constructed using the most highly expressed genes in post-mortem brain samples of patients.
Overlapping 4- and 5-node cliques, with nodes ranked high in centrality analyse, were identified in these sub-networks and proposed as the “central functional modules” of BA10 and BA46 samples. A few “switchboard” nodes were found to form PPIs with nodes which were abnormally expressed in multiple diseases. PPIs which were unique to a disease or shared between two (or more) diseases were also observed.
Genes which abnormally expressed in the brain samples of patients and associated with the central functional modules were proposed as disease markers. These marker genes were also proposed as targets for drug treatment.