NARSAD Grantee Leads Team That Links Two Risk Factors for Schizophrenia

Mikhail V. Pletnikov, M.D., Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, expert on schizophrenia
Mikhail Pletnikov, M.D., Ph.D.

In a new study published in the journal Molecular Psychiatry, Johns Hopkins researchers have discovered that two previously established biological risk factors for schizophrenia have a cause-and-effect relationship.

The study was led by Mikhail V. Pletnikov, M.D., Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, in collaboration with Scientific Council member Solomon H. Snyder, M.D., D.Sc. , who heads the Solomon H. Snyder Department of Neuroscience at Johns Hopkins.

Previous studies have demonstrated the role played by the Disrupted-in-Schizophrenia 1 (DISC1) gene in neurons and have linked a mutation in this gene to an increased risk of developing schizophrenia. Decreased glutamate transmission has also been associated with schizophrenia. In this new study, the Johns Hopkins researchers looked at the role the DISC1 gene plays in glia cells known as astrocytes, a kind of support cell in the brain that helps neurons communicate with one another. One of the roles of astrocytes is to secrete the neurotransmitter D-serine, which helps promote the transmission of glutamate in the brain. They found that people with DISC1 mutations associated with schizophrenia are faster to metabolize D-serine, which leads to a decrease in the apparently crucial transmitter.

Dr. Pletnikov, who received a NARSAD Independent Investigator Grant in 2008, said "abnormalities in glia cells could be as important as abnormalities in neuronal cells themselves. Most gene work has been done with neurons. But we also need to understand a lot more about the role that genetic mutations in glia cells play because neuron-glia interaction appears crucial in ensuring the brain operates normally."

The findings could eventually lead researchers to develop better drugs to treat abnormal glutamate transmission in schizophrenia as well as bipolar disorder, major depression and possibly anxiety disorders.

Read more about this fascinating research about the biological risk factors for schizophrenia