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

Participation Requirements

• Sex:

  ALL

• Eligible Ages:

  17 to 45

Participation Criteria

Inclusion Criteria:

i) Experimental group (participants with a diagnosis of schizophrenia spectrum disorder):

1. Antipsychotic naïve or antipsychotic treatment for equal to or less than 3 weeks within the past 3 months
2. (Medications can be confirmed via CAMH chart review). Participants do not need to remain off of antipsychotics for the duration of the study.
3. 17-45 years
4. both sexes;
5. 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).
6. BMI under or equal to 27
7. Right-handed

ii) Control group (healthy controls):

1. 17-45 years of age
2. sex-,
3. hand dominance (right-handed) -and
4. body mass index (BMI)-matched
5. Absence of DSM-5 diagnosis other than a specific phobia according to MINI

Exclusion Criteria:

1) moderate or severe substance use according to MINI (per PI discretion in the case of moderate alcohol or cannabis use)

1. prediabetes, diabetes, or evidence of impaired glucose tolerance on screening OGTT
2. acute suicidal risk
3. use of weight, lipid, antidiabetic or blood pressure reducing agents
4. liver or kidney disease
5. pregnancy
6. nursing
7. pacemakers
8. metallic cardiac valves
9. magnetic material such as surgical clips, implanted electronic infusion pumps or any other conditions that would preclude the MRI scan
10. clinically significant claustrophobia (determined from MRI screening form; significance evaluated as per QI's discretion).
11. history of head trauma resulting in loss of consciousness \> 30 minutes that required medical attention;
12. size of head, neck, precluding to fit in the MRI or PET scanners
13. weight over 350lbs (limit for MRI scanner bed)
14. unstable physical illness
15. significant neurological disorder including a seizure disorder;
16. Received maximum allowed radiation in the past 12 months (20 mSv)
17. 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.
18. clinically relevant abnormality observed in medical history,
19. 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).
20. Disorders of coagulation, blood or ongoing use of anticoagulant medication

Control group: Exclusionary criteria are as listed above for participants, in addition to:

1) First degree family member with primary psychotic disorder.