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.
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
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
Crossover
Intranasal insulin
Drug160 IU insulin (Humalog) is administered intranasally using a metered spray bottle 15 minutes prior to the PET scan.
Placebo
Drug0.9% saline is administered intranasally using a metered spray bottle 15 minutes prior to the PET scan.
[18F]-FDG brain uptake
Change in \[18F\]-FDG uptake in striatum and hippocampus is measured in response to intranasal insulin challenge or placebo
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