Decrease of serotonin receptor 2C in schizophrenia brains identified by high-resolution mRNA expression analysis

Background: RNA expression profiling can provide hints for the selection of candidate susceptibility genes, for formulation of hypotheses about the development of a disease, and/or for selection of candidate gene targets for novel drug development. We measured messenger RNA expression levels of 16 candidate genes in brain samples from 55 schizophrenia patients and 55 controls. This is the largest sample so far used to identify genes differentially expressed in schizophrenia brains. Methods: We used a sensitive real-time polymerase chain reaction methodology and a novel statistical approach, including the development of a linear model of analysis of covariance type. Results: We found two genes differentially expressed: monoamine oxidase B was significantly increased in schizophrenia brain (p = .001), whereas one of the serotonin receptor genes, serotonin receptor 2C, was significantly decreased (p = .001). Other genes, previously proposed to be differentially expressed in schizophrenia brain, were invariant in our analysis. Conclusions: The differential expression of serotonin receptor 2C is particularly relevant for the development of new atypical antipsychotic drugs. The strategy presented here is useful to evaluate hypothesizes for the development of the disease proposed by other investigators.