CHAMPAIGN-URBANA, Ill. (WCIA) -- Researchers at the University of Illinois have found a direct link between a genetic mutation and schizophrenia.

The scientists found a genetic mutation that two humans with schizophrenia had also led to increased "schizophrenia-related behaviors" in mice with the same mutation. According to the U of I News Bureau, the mutation increases levels of glycine decarboxylase (GLDC), which regulates glycine in the brain.

"The genetics of schizophrenia is very complex, and it is rare that mutations found in patients can be linked directly to the disease," study leader Uwe Rudolph, a professor of comparative biosciences at Illinois, said. "Schizophrenia is not yet diagnosed by any kind of lab test or imaging; it's still a clinical diagnosis based on symptoms. The hope is that these kinds of rare mutations could lead us to the biochemical and physiological pathways that are important to study."

The study first began when scientists in Massachusetts found a genetic mutation in two patients with schizophrenia. They had several copies of a section of DNA which included the gene for GLDC. The team studying the patients coordinated with Rudolph's lab to create mice with the same mutation.

After examining the mice with the mutations, scientists determined that they did show schizophrenia-associated behaviors. But, the scientists wanted to narrow the link down even more. They made more mice with copies of a few genes within the larger chromosome. Then they narrowed it down further to a single gene: GLDC.

"We found that extra copies of the GLDC gene alone were sufficient to render the schizophrenia-like behaviors we had observed," Rudolph said.

Next, the researchers took a closer look at the brains of the mice.

"We hypothesized that extra copies of GLDC would result in a lower level of glycine in the brain, since it degrades glycine. Then there would not be enough glycine to help activate the NDMA receptors," Illinois postdoctoral researcher Maltesh Kambali, the first author of the paper, said. "We measured an increase in activity of the GLDC enzyme in the brains of our mice, which would point to that as well."

But, when measuring glycine levels in the brains of the mice, there was not a significant difference between the mice with the extra GLDC and healthy mice.

The scientists turned to their colleagues in Germany who had discovered a way to track glycine in the brain. The Germans found that the overall amount of glycine in the whole brain was similar. But, there were significantly lower levels in a subregion of the hippocampus, called the dentate gyrus, in the mutated mice.

Next, the scientists teamed up with researchers at Harvard to find out why this part of the brain was so affected. They found less activity in the neural synapse, which sends signals to neurons.

"We saw how glycine measurements and the long-term potentiation measurements were showing converging changes in this dentate gyrus region, but not in other regions of the hippocampus. It's interesting because one theory links the development of psychosis to the activity in the dentate gyrus. So, our findings fit with that theory," Kambali said.

Next, the Illinois team analyzed the dentate gyrus in the mice with the extra GLDC copies. They found that an increase of GLDC and a decrease of glycine could inhibit the function of NMDA receptors, and could contribute to schizophrenia symptoms.

"This study demonstrated at multiple levels how GLDC functions as a novel regulator of NMDA receptors," Rudolph said. "Dysfunction of NMDA receptors has been shown to be important in the pathophysiology of schizophrenia. Yet this finding also is relevant independently of disease, as the NMDA receptor is essential for many brain functions, including learning and memory."

You can read more about the team's findings in the journal of Molecular Psychiatry here.