Gene interaction linked to schizophrenia

The researchers developed a model of schizophrenia that provides a way to study and understand how the loss of both Prodh and Comt gene activity contributes to the symptoms of schizophrenia.

Results of studies show that disruption of the normal interaction between the two genes contributes directly to major symptoms of the illness by upsetting the balance of the neurotransmitters glutamate and dopamine, which have previously been implicated in the development of schizophrenia.

The team investigated the roles of Prodh and Comt because these genes are located in the q11 region of human chromosome 22; previous studies show that a mutation in this region is one of the major risk factors for developing schizophrenia.

The key finding in the current study was that the models of Prodh deficiency had increased Comt activity in the frontal cortex of the brain.

“This might reflect a response to the increased dopamine activity caused by Prodh deficiency,” said Dr Stanislav Zakharenko, an assistant member of the Department of Developmental Neurobiology at St Jude Children’s Research Hospital. “And it shows that when Prodh is lost, the additional loss of Comt due to the 22q11 mutation may worsen the symptoms of schizophrenia by allowing dopamine levels to rise.”