Identification of novel candidate genes for schizophrenia: using postmortem brain study

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In our Scientific Research (C)(2) project from 2000 to 2002, we found changes in several signal transduction systems in the brains of animal models for schizophrenia, and the postmortem brains of schizophrenia. In addition, we analyzed gene expression in the postmortem brains of schizophrenia, in order to identify novel candidate genes for schizophrenia.1) We found that calcineurin proteins decreased, while phosphothreonine-DARPP-32 increased in the striatum of Meth-sensitized rats. These results indicate that the activity of signal transduction via CaN is functionally decreased in the striatum of Meth-sensitized rats.2) A deteriorated serotonin2A receptor-G protein q alpha (Gq alpha) -phosphoinositide-specific phospholipase C beta1 (PLC beta1) cascade has been found in the left, but not right, the superior temporal cortex of patients with schizophrenia.3) We screened for genetic variations in the region of the NR2B subunit gene encoding the carboxyl-terminal intracellular domain in patients with schizophrenia and studied the association between schizophrenia and a novel polymorphism of the NR2B subunit gene. One silent mutation (2664C/T) was identified. No significant differences in the frequencies of 2664C/T genotypes and alleles were found between patients with schizophrenia and healthy comparison subjects.4) We searched for genes that are induced by phencyclidine using the mRNA differential-display technique. Analyses of the nucleus accumbens of the treated animals and matched controls revealed changes in the expression of genes related to glutamatergic transmission and the intracellular transmission in the brain of the animal model for schizophrenia.5) We investigated gene expression patterns in brain regions of patients with schizophrenia. A cDNA array was used to screen pools of samples from the prefrontal cortex of patients with schizophrenia. Of the examined genes, 33 mRNA were increased and 22 were decreased.