Response to Clozapine in Treatment Resistant Schizophrenia: A Longitudinal Magnetic Resonance Spectroscopy Study

This study will be a prospective proton spectroscopy (1H-MRS) study designed to compare the levels of glutamate, glutamine, glx, and glutathione in age- and gender- matched patients with poor response to clozapine (URS), patients with good response to clozapine (non-URS), and healthy controls. Participants with schizophrenia who fail to respond to optimal treatment with at least two different non-clozapine antipsychotics (i.e. treatment-resistant schizophrenia \[TRS\]) and who are starting clozapine as part of their clinical care will be recruited. A sample of healthy controls will also be recruited. Participants with TRS will have two 1H-MRS scans. The 1H-MRS scan will be performed within 1 week and 12 weeks after clozapine initiation. Clinical assessments will be performed within 1 week of each 1H-MRS scan and after 6 weeks of clozapine treatment. Cognitive assessments will also be performed within 1 week of 1H-MRS scans. Healthy controls will also undergo two 1H-MRS scans with a 12-week interval. Cognitive assessments will also be performed within 1 week of 1H-MRS scans.