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

• Status: Not yet recruiting
• Trial end date: 2025-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Cognitive impairment (such as challenges in thinking and memory) is a core aspect of schizophrenia (SCZ), contributing to disability and poor functional outcomes. Additionally, almost half of the patients with SCZ are obese, the prevalence of type 2 diabetes is 3-6 times higher, and life expectancy is lower by 15-20 years compared to the general population. This is relevant as metabolic syndrome and diabetes are both associated with worse cognition among SCZ patients. Recent work studying the relationships between metabolic health and cognition has encouraged a new way of thinking about SCZ as both a metabolic and cognitive disorder. Brain insulin is involved in several processes relevant to SCZ, and abnormal brain insulin action may help explain both cognitive and metabolic abnormalities in patients with SCZ, but this has not been examined previously. Glucose uptake in several brain regions relevant to SCZ has been shown to be partially dependent on insulin. Therefore, in this study, the researchers will measure glucose uptake in the brain using an 18F-fluorodeoxyglucose ([18F]-FDG) positron emission tomography (PET) scan after an intranasal insulin stimulus, and will compare this measure between patients with SCZ and healthy controls.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Centre for Addiction and Mental Health
• Treatments: Insulin; Insulin Lispro

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.