Singapore: An excess of the brain neurotransmitter, glutamate, may cause a transition to psychosis in people who are at risk for schizophrenia, reports a study from investigators at Columbia University Medical Center (CUMC). The study has been published in the current issue of Neuron.

The findings suggest a potential diagnostic tool for identifying those at risk for schizophrenia and a possible glutamate-limiting treatment strategy to prevent or slow progression of schizophrenia and related psychotic disorders.

"Previous studies of schizophrenia have shown that hypermetabolism and atrophy of the hippocampus are among the most prominent changes in the patient's brain," said senior author Dr Scott Small, Boris and Rose Katz Professor of Neurology at CUMC. "The most recent findings had suggested that these changes occur very early in the disease, which may point to a brain process that could be detected even before the disease begins."

The Columbia researchers used neuroimaging tools in both patients and a mouse model for their research. First they followed a group of 25 young people at risk for schizophrenia to determine what happens to the brain as patients develop the disorder. In patients who progressed to schizophrenia, they found a particular pattern. First, glutamate activity increased in the hippocampus, then hippocampus metabolism increased, and then the hippocampus began to atrophy.

To see if the increase in glutamate led to the other hippocampus changes, the researchers turned to a mouse model of schizophrenia. When the researchers increased glutamate activity in the mouse, they saw the same pattern as seen in the patients. The hippocampus became hypermetabolic and, if glutamate was raised repeatedly, the hippocampus began to atrophy.