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 inc…