| Outcome Measures: |
Primary: The change in brain imaging outcomes, measuring brain insulin resistance, following intranasal insulin or placebo challenges, compared between the participants with depression and healthy controls., Brain insulin resistance will be measured by changes in fMRI, 1H- MRS, and ASL measured during MRI scans following intranasal insulin and placebo challenge. These changes will be compared within subjects and between groups (depression vs controls). 1. Resting state functional MRI (fMRI) will measure connectivity between prefrontal brain regions and hippocampus. 2. Single voxel proton magnetic resonance spectroscopy (1H- MRS) will measure the glutamate levels in the temporal and frontal cortex. 3. Arterial spin labeling (ASL) will be used to measure cerebral blood flow in the hypothalamus and the prefrontal cortex., Study Visit 1- MRI #1 15 minutes after intranasal challenge #1, MRI #2 15 minutes after intranasal challenge #2 | Secondary: Correlation between brain insulin resistance with illness severity and cognitive functioning at baseline and 6-month study follow up, Primary outcome measures will be used to assess the correlation between brain insulin resistance (MRI measures; described in Outcome 1) and illness severity. Illness Severity- Center for Epidemiological Studies- Depression Scale for Children (CES-DC). 20 item self-report depression inventory with possible scores ranging from 0-60. Higher scores are indicative of worse illness severity. A cut-off score of 15 is suggestive of depressive symptoms in children and adolescents., Illness Severity: Study Visit 1, pre-intervention (MRI scan #1), and 6-month follow-up study visit following fasting blood work; Brain Insulin Resistance: Study Visit 1, during MRI scan #1 and #2|Correlation between brain insulin resistance with cognitive functioning at baseline and 6-month study follow up, Primary outcome measures will be used to assess the correlation between brain insulin resistance (MRI measures; described in Outcome 1) with cognitive functioning. Cognitive Functioning- THINC-it® (interactive cognitive assessment tool). Brief screening tool designed to measure cognition and determine whether cognitive functioning is impaired. Higher score is indicative of better performance, scores can range from 0-4000., Cognitive Function: Study Visit 1, during break between MRI scan #1 and #2, and 6-month follow-up study visit following fasting blood work; Brain Insulin Resistance: Study Visit 1, during MRI scan #1 and #2 | Other: Correlation between brain insulin resistance and peripheral insulin resistance at baseline and 6-month study follow up, Primary outcome measures will be used to assess the correlation between brain insulin resistance (MRI measures; described in Outcome 1) with peripheral insulin resistance. Peripheral Insulin Resistance - Fasting bloodwork: Glucose (mmol/L), insulin (pmol/L), C-peptide (pmol/L)., Peripheral Insulin Resistance: Study Visit 1, pre-MRI #1 and post-MRI #2, and 6-month follow-up study visit; Brain Insulin Resistance: Study Visit 1, during MRI scan #1 and #2|Correlation between brain insulin resistance, and hepatic and visceral adiposity, Primary outcome measures will be used to assess the correlation between brain insulin resistance (MRI measures; desired in Outcome 1) with hepatic and visceral adiposity Hepatic and Visceral Adiposity- Abdominal MRI Scan (cm\^3), Hepatic and Visceral Adiposity: Study Visit 1, during MRI #1; Brain Insulin Resistance: Study Visit 1, during MRI scan #1 and #2
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