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    Stanislov S. Zakharenko, MD, PhD

    Stanislav S. Zakharenko, MD, PhD

    Genetic disruption contributes to schizophrenia

    Disrupting the normal interaction between the genes PRODH and COMT contributes to major symptoms of schizophrenia by upsetting the balance of the brain chemicals glutamate and dopamine, according to a group of investigators that includes a scientist now at St. Jude Children's Research Hospital.

    The investigators developed a model of schizophrenia that provides a way to study and understand how the loss of PRODH and COMT gene activity contributes to the symptoms of schizophrenia.

    The loss of the PRODH gene causes an imbalance in the levels of both glutamate and dopamine; this imbalance contributes directly to the symptoms of schizophrenia, according to Stanislav Zakharenko, MD, PhD, of the St. Jude department of Developmental Neurobiology. Zakharenko, formerly at Columbia University, is a co-author of a report on this work that appeared in the November 15 issue of Nature Neuroscience.

    It was already known that the PRODH and COMT genes are located in the q11 region of human chromosome 22, and that a mutation in this region—the 22q11 microdeletion—is one of the chief 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," Zakharenko said. "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."

    St. Jude does both laboratory and clinical research in order to find cures for catastrophic diseases of children. Much of this research, especially in the laboratory, leads to discoveries of the basic workings of the body's cells. Therefore, some of our work has broader implications than childhood diseases and provides insights into adult diseases as well.

    Last update: January 2006