Grant: CIHR Fellowship

Schizophrenia is a chronic, progressive mental illness that affects up to 1% of the population and carries an enormously personal, health, and economic cost. An abnormal increase in dopamine in the brain is thought to result in schizophrenia. The current treatment for schizophrenia includes medications named antipsychotics to block the action of dopamine. Unfortunately, antipsychotics are not working in 30% of patients. Glutamate (Glu) is the most prevalent neurotransmitter in the brain and plays an integral role in every brain function. Increased Glu levels are found in patients with schizophrenia during the first stages of their illness. The increased Glu levels are normalized after effective antipsychotic treatment. However, no research has investigated Glu levels in those patients who show no response to antipsychotics. Glu can be measured in the brain by a technique called Magnetic Resonance Spectroscopy (MRS). This is a non-invasive procedure to measure different substances in the brain without any injection or discomfort. This study will measure Glu levels using MRS in the brain in patients with schizophrenia with no response to antipsychotics. The Glu levels of 25 patients with no response will be compared with 25 patients with good response to antipsychotics and healthy individuals. Glu levels will be measured in an area of the brain called the striatum, which has previously shown abnormally increased levels of dopamine and Glu. This is the first study to measure Glu in patients with no response to antipsychotics. If our hypothesis is correct, we will be able to demonstrate increased Glu levels in patients with treatment resistant schizophrenia compared to those with good response to antipsychotics and the healthy controls. Such findings may increase understanding of schizophrenia and facilitate the development of new medications for schizophrenia targeting the normalization of Glu.