Grant: Operating Grant

Schizophrenia is a chronic, progressive mental illness that affects up to 1% of the population and is the 5th leading causes of disability in industrialized countries. Unfortunately, the current treatment for schizophrenia with antipsychotics are not working in about 20% to 35% of the patients. Glutamate is a substance or neurotransmitter normally present in the brain; it is the most prominent excitatory neurotransmitter in the brain and reported to be increased in the brain of patients with schizophrenia. Glutathione is a major antioxidant in the brain and is involved in the neutralization of free radicals that may damage the cells in the brain. In addition, glutathione can modify the levels of glutamate in the brain and the 'potency' by which glutamate works in the brain. Decreased levels of glutathione have been found in schizophrenia and increasing glutathione levels have improved some of the symptoms in schizophrenia. However, no research has been performed to investigate the levels of glutathione in the brains of those patients who do not respond well to antipsychotic treatment. Further, no research has directly investigated the relationship between glutathione and glutamate in schizophrenia. We will recruit patients with schizophrenia with no response to common antipsychotic medications and healthy controls for comparison. Glutamate and glutathione levels will be measured in several brain regions associated with schizophrenia using a non-invasive technique called Proton Magnetic Resonance Spectroscopy and will be compared across the groups of participants using mathematical models. If our hypothesis is correct, we are able to demonstrate abnormal levels and altered relationship between glutamate and glutathione in patients with treatment resistant schizophrenia. The results will help to guide new future treatments and increase understanding of anomalies in schizophrenia.