Modulating the Glutamate/Glumathione System in Schizophrenia: An MRS-Based Study

Ragy Girgis, M.D.

College of Physicians and Surgeons of Columbia University , New York, NY

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

December 2013, for 3 years

Funding Amount:


Lay Summary

Utilizing MRS imaging to assess potential experimental therapies for treating schizophrenia

This research is designed to determine whether MRS imaging (Magnetic Resonance Spectroscopy) can assess the effects of experimental therapies in increasing glutamate levels to treat schizophrenia.

Currently schizophrenia is treated with antipsychotic medications. These drugs act by blocking receptors on brain cells that use the neurotransmitter dopamine. Excess dopamine levels have been associated with symptoms of schizophrenia, and antipsychotics have demonstrated the capacity to modulate symptoms in many patients to enable them to function. Antipsychotics have limited efficacy, however, and often produce serious side effects including weight gain and associated diabetes, and difficulties concentrating. Researchers continue to search for improved therapies based on disease processes and in recent years have been exploring the potential role of another neurotransmitter—glutamate—in schizophrenia. Clinical studies have found that people with schizophrenia tend to have lower than normal levels of glutamate, and that lower levels are associated with more severe symptoms.

Glutamate activity can be stimulated by a chemical in the body called glutathione. Initial observation in a small number of people with schizophrenia using an anti-oxidant available at health food stores, called “NAC” (N-acetylcsteine), suggests that NAC may increase glutamate activity and may improve some symptoms of schizophrenia. The Columbia University researchers, using MRS imaging, recently found in a small number of people with schizophrenia that NAC increased glutathione, the chemical that stimulates glutamate activity. MRS imaging is a non-invasive technique that measures biochemical changes in the brain over time, characterizing brain diseases according to the national history of the chemical changes that are produced.

The Columbia University researchers now will use MRS imaging in 20 adults with schizophrenia and 20 healthy volunteers to determine: 1) whether glutathione levels in people with schizophrenia are lower than those in healthy volunteers; 2) whether NAC increases glutathione levels in people with schizophrenia but not in the volunteers; and 3) whether greater severity of symptoms in people with schizophrenia will be associated with lower levels of glutathione.

Significance: The findings may help to establish the utility of using MRS to assess the effects of experimental therapies such as NAC in stimulating the glutamate system and correlating the effects with symptomatic improvement. The findings also may reveal whether MRS can be used to determine optimal doses of such medications.