Glutamate Levels in the Brain Accelerate Progression of Schizophrenia

Excess amounts of glutamate - a neurotransmitter - in the brain may demonstrate signs of schizophrenia progressing to psychosis, a new study has shown.

According to National Institute of Mental Health, schizophrenia is a chronic, severe, and disabling brain disorder that has affected people throughout history. People with this disorder hear voices that others don't hear. They may also believe that others are plotting against them. These people may become agitated and withdraw themselves from society.

The study was conducted by researchers from Columbia University Medical Center (CUMC). The research findings have two major implications; firstly, glutamate levels can be assessed to know the progression of the condition, and secondly, glutamate levels can be controlled in the people who are at high risk of developing psychosis.

The study was based on both patients and mouse models. In about 25 young people who were at risk for schizophrenia, researchers found that the disease usually progresses with the increase of glutamate activity. The increase in the neurotransmitter level then leads to increase in activity in the hippocampus which further leads to increase in hippocampus metabolism, and ultimate atrophy of the hippocampus.

Glutamate is the most important transmitter in a normal brain, and about half of all brain synapses release it. However, elevated levels of the agent following a neural injury can be toxic to the neurons.

Many studies have looked at the changes in the hippocampus and development of schizophrenia; with deflation of the region being associated with severity of the condition. The hippocampus is the region of the brain where consolidation of memory from short-term to long-term takes place. The hippocampus is also the first region to be affected by certain other neurological diseases like Alzheimer's disease.

"Previous studies of schizophrenia have shown that hypermetabolism and atrophy of the hippocampus are among the most prominent changes in the patient's brain. 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," said Scott Small, MD, Boris and Rose Katz Professor of Neurology at CUMC and senior author of the study, according to a news release.

Researchers then looked at the brains of the mouse models to see if glutamate levels were playing a part in the progression of the condition. They found that increase in glutamate activity in the brain of the mouse led to the kind of changes that the researchers had observed in the brains of schizophrenia patients. The hippocampus in the mouse brain increased activity, and then began to atrophy or waste away.

Controlling glutamate levels in people with schizophrenia has been tried before, but only in people who were at the advanced stages of the disease.

"Targeting glutamate may be more useful in high-risk people or in those with early signs of the disorder," said Jeffrey A. Lieberman, MD, expert in the field of schizophrenia, Chair of the Department of Psychiatry at CUMC. "Early intervention may prevent the debilitating effects of schizophrenia, increasing recovery in one of humankind's most costly mental disorders."

About 1 percent of all Americans have this disorder, NIMH says. People with schizophrenia are usually not violent. The risk of suicide is higher by about 10 percent, especially in young males.

The study is published in the journal Neuron.