Emerging research suggests an excess of the brain neurotransmitter glutamate may cause a transition to psychosis in people who are at risk for schizophrenia.
Columbia University Medical Center (CUMC) scientists believe the discovery may help to identify those at risk for schizophrenia.
Furthermore, experts believe a possible glutamate-limiting treatment strategy cold prevent or slow progression of schizophrenia and related psychotic disorders.
Study findings are published in the current issue of the journal Neuron.
“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 Scott Small, M.D.
“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.”
Columbia researchers used neuroimaging tools in both patients and a mouse model to discover the process. Researchers first 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 the following 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 in the patients: The hippocampus became hypermetabolic and, if glutamate was raised repeatedly, the hippocampus began to atrophy.
Conceptually, this dysregulation of glutamate and hypermetabolism could be identified through imaging individuals who are either at risk for or in the early stage of disease. For these patients, treatment to control glutamate release might protect the hippocampus and prevent or slow the progression of psychosis.
Experts say that strategies to treat schizophrenia by reducing glutamate have been tried before, but with patients in whom the disease is more advanced.
“Targeting glutamate may be more useful in high-risk people or in those with early signs of the disorder,” said Jeffrey A. Lieberman, M.D., a renowned expert in the field of schizophrenia.
“Early intervention may prevent the debilitating effects of schizophrenia, increasing recovery in one of humankind’s most costly mental disorders.”
In an accompanying commentary, experts suggest that if excess glutamate is driving schizophrenia in high-risk individuals, it may also explain why a patient’s first psychotic episodes are often caused by periods of stress, since stress increases glutamate levels in the brain.
Brain image available from Shutterstock