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

Inclusion Criteria for Participants with TRS: * DSM-IV/SCID diagnosis of schizophrenia, schizoaffective disorder, delusional disorder, or psychotic disorder NOS. * Age 18 years or older at time of scanning * History of failure to respond to at least two previous sequential antipsychotic treatments different to clozapine, each attaining a chlorpromazine daily dose of≥ 400 mg for a duration ≥ 6 consecutive weeks.Long-acting antipsychotic treatment will not be allowed during the last trial prior to clozapine in order to avoid residual concentrations or effects.Failure of treatment will be defined by a Clinical Global Impression Severity (CGI-Severity) score of ≥4 and score of ≥4 on 2 Positive and Negative Syndrome Scale (PANSS) positive symptom items. The CGI-Severity or Global Assessment of Functioning (GAF) will be completed retrospectively based on information provided by the participant, participant's psychiatrist, medical chart, or other sources of available collateral information. Exclusion Criteria for Participants with TRS: * Incapacity to provide consent to participate in the research study. * Substance abuse or dependence (within past six months), excluding nicotine and caffeine. * Positive urine drug screen for drugs of abuse. * Metal implants or a pace-maker that would preclude the MRI scan. * History of head trauma resulting in loss of consciousness \> 30 minutes that required medical attention. * Unstable physical illness or significant neurological disorder including a seizure disorder. * Size of head, neck, and body being unable to fit MRI scanners. * Refusal to provide consent to investigator to communicate with physician of record to obtain collateral information. * Psychiatric concerns raised by the physician of record regarding participation in the study. * Currently taking medications that may directly impact the glutamatergic system (i.e. lamotrigine, topiramate, memantine or N-acetylcysteine) * ECT, MST or TMS in the past 6 months Inclusion criteria for Healthy Controls: * Age of 18 and older at time of scanning * Being capable to consent to study procedures * Absence of history of psychiatric illness using the Mini-International Neuropsychiatric Interview (MINI) Exclusion criteria for Healthy Controls: * First degree family member with primary psychotic disorder * Substance abuse or dependence (within past six months), excluding nicotine and caffeine. * Positive urine drug screen for drugs of abuse * Pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or any other conditions that would preclude the MRI scan * Clinically significant claustrophobia * History of head trauma resulting in loss of consciousness \> 30 minutes that required medical attention * Size of head, neck, and body being unable to fit MRI scanners * Unstable physical illness or significant neurological disorder including a seizure disorder