Does Abnormal Insulin Action in the Brain Underlie Cognitive and Metabolic Dysfunction in Schizophrenia

Inclusion criteria

• i) Experimental group (participants with a diagnosis of schizophrenia spectrum disorder):
• 17-45 years
• both sexes;
• Patients with first-episode schizophrenia spectrum illness: Primary DSM-5 diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, brief psychotic disorder, psychotic disorder NOS, major depressive disorder with psychotic symptoms, bipolar I disorder, and bipolar II disorder, OR substance-induced psychosis, and antipsychotic treatment for schizophrenia, schizoaffective disorder, or other specified schizophrenia spectrum, other psychotic disorder, major depressive disorder with psychotic symptoms, bipolar I disorder, and bipolar II. (Diagnosis willbe confirmed via CAMH chart review).
• BMI under or equal to 27
• ii) Control group (healthy controls):
• 17-45 years of age
• sex-,
• hand dominance -and
• body mass index (BMI)-matched
• Absence of DSM-5 diagnosis other than a specific phobia according to MINI

Exclusion criteria

• moderate or severe substance use according to MINI (per PI discretion in the case of moderate alcohol or cannabis use)
• prediabetes, diabetes, or evidence of impaired glucose tolerance on screening OGTT
• acute suicidal risk
• use of weight, lipid, antidiabetic or blood pressure reducing agents
• liver or kidney disease
• pregnancy
• nursing
• 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 (determined from MRI screening form; significance evaluated as per QI's discretion).
• history of head trauma resulting in loss of consciousness \> 30 minutes that required medical attention;
• size of head, neck, precluding to fit in the MRI or PET scanners
• weight over 350lbs (limit for MRI scanner bed)
• unstable physical illness
• significant neurological disorder including a seizure disorder;
• Received maximum allowed radiation in the past 12 months (20 mSv)
• Completed more than 6 PET scans/ lifetime, that, together with the PET scanning procedures under this protocol will bring the total number of PET scans to more than the allowed/lifetime (8 PET scans per lifetime). These limits are set by the Centre for Addiction and Mental Health Brain Health Imaging Centre Guideline.
• clinically relevant abnormality observed in medical history,
• current intake of any medication that may interfere with participation in the study or may confound the results of PET imaging (e.g. anti-diabetic medication).
• Disorders of coagulation, blood or ongoing use of anticoagulant medication
• Control group: Exclusionary criteria are as listed above for participants, in addition to:
• \) First degree family member with primary psychotic disorder.