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Understanding Glutamate and Psychosis Offers Hope for Schizophrenia

By Traci Pedersen Associate News Editor Reviewed by John M. Grohol, Psy.D. on October 1, 2010 New research has discovered that when there is an abnormal relationship between dopamine and glutamate two signaling chemicals in the brain the result is often psychosis. The study offers a new angle in understanding psychotic symptoms, possibly leading to more effective drugs for schizophrenia. Schizophrenia is one of the most common severe mental health disorders. Those with the disorder may suffer through the troubling symptoms of psychosis an inability to tell the difference between reality and imagination including delusions and hallucinations. The disorder often begins in the late teens or 20s, and usually continues throughout the rest of the persons life. Chemicals in the brain called neurotransmitters deliver signals from one nerve cell to another. Previous studies have linked schizophrenia to unusually high levels of a neurotransmitter called dopamine in an area of the brain called the striatum. Current drugs used to treat schizophrenia hamper the effects of dopamine in the brain. These drugs, however, are not successful in all patients, and often carry harmful side effects. The new findings unveil the fact that the high levels of dopamine found in people with psychotic symptoms actually occur as a result of changes in another brain chemical, glutamate. Scientists discovered that brain cells that release glutamate in the hippocampus connect to the striatum and have a direct influence on the activity of dopamine-releasing cells. This research shows that if a drug were to interfere with glutamate signals in the brain, psychotic symptoms in people with schizophrenia may be prevented. Schizophrenia is a devastating illness that destroys the lives of people who are afflicted and those around them, said Dr. James Stone of the Department of Medicine at Imperial College London, first author of the study. At the moment, the drugs we have just arent adequate. They dont help everybody, and they dont stop some of the most debilitating symptoms. For the study, scientists took brain scans of 16 people who had an at-risk mental state for psychosis and 12 healthy volunteers, in order to measure each groups levels of glutamate and dopamine. In people with early signs of psychotic symptoms, there was an abnormal relationship between glutamate levels in the hippocampus and dopamine levels in the striatum. There was even greater evidence of this in the participants who later went on to develop psychosis. In the healthy subjects, however, there was no negative correlation. In healthy volunteers, theres no clear relationship between glutamate and dopamine, but in people with early signs of psychosis, we see this abnormal relationship, Dr. Stone said. This suggests that the signaling pathway between the hippocampus and the striatum is dysfunctional, and we might be able to treat this by targeting the glutamate system. If drugs that act on glutamate signalling can prevent psychotic symptoms, it would mean a real shift in the way that people are treated for schizophrenia. The next step will be to see if these results are confirmed in a larger group of people. There are already a

number of promising drug candidates that interfere with glutamate signaling, so hopefully in a few years well be able to start testing new treatments for people with schizophrenia. Professor Chris Kennard, chair of the MRC Neuroscience and Mental Health Board, said, Studies like these are helping to unravel the complex mechanisms of psychiatric illness and bring us a step closer to more effective, targeted drugs for patients with schizophrenia. The MRC funds research like this in order to bring scientific findings from the lab bench to patient bedside, more quickly. If we can develop new drugs that prevent psychotic symptoms, it would mean a real benefit for patients with schizophrenia. The study is published in journal Biological Psychiatry and was funded by the Medical Research Council (MRC). Source: Imperial College London