Inclusion Criteria:
Body Mass Index 24-34.9
HEALTHY CONTROLS HOMA-IR (fasting (glucose x insulin)/405) < 1.8
Not more than one of the following:
- Waist circumference > 40 inches (men) or > 35 inches (women)
- Triglycerides > 150 mg/dL
- HDL < 40 mg/dL (men) or < 50 mg/dL (women)
- Blood pressure > 135/85
- Fasting glucose > 100 mg/dL
INSULIN RESISTANT HOMA-IR > 2.0
And at least three of the following:
- Waist circumference > 40 inches (men) or >35 inches (women)
- Triglycerides > 150 mg/dL
- HDL < 40 mg/dL (men) or <50 mg/dL (women)
- Blood pressure > 135/85
- Fasting glucose > 100 mg/dL
MAJOR DEPRESSION, METABOLICALLY HEALTHY Meets criteria for MDD during SCID-5 evaluation HOMA-IR < 1.8
Not more than one of the following:
- Waist circumference > 40 inches (men) or >35 inches (women)
- Triglycerides > 150 mg/dL
- HDL < 40 mg/dL (men) or <50 mg/dL (women)
- Blood pressure > 135/85
- Fasting glucose > 100 mg/dL
MAJOR DEPRESSION, INSULIN RESISTANT Meets criteria for MDD during SCID-5 evaluation HOMA-IR > 2.0
And at least three of the following:
- Waist circumference > 40 inches (men) or >35 inches (women)
- Triglycerides > 150 mg/dL
- HDL < 40 mg/dL (men) or <50 mg/dL (women)
- Blood pressure > 135/85
- Fasting glucose > 100 mg/dL
Exclusion Criteria:
- - History of mania or psychosis
- Current suicidal ideation
- Alcohol or substance abuse including cannabis use (current or in the last three months)
- Early onset dementia of any etiology
- Medical conditions with known significant effects on mood (e.g. Stroke or current hypothyroid state)
- Unstable medical illnesses (e.g. Delirium, uncontrolled DM, uncontrolled cardiovascular illness)
- Use of high doses of benzodiazepines (> 2mg lorazepam/day equivalent)
- Given the high comorbidity (80%) between MDD and anxiety disorders, participants with comorbid anxiety disorders will be included in the study as long as the clinical presentation suggests that depression precedes the onset of anxiety
- Current or lifetime history of cancer, a chronic kidney or liver condition, type I or II diabetes
- Current or lifetime use of glucocorticoid medications for >1 month
- Previous cerebrovascular accident or trauma involving loss of consciousness
- Previous neurosurgery or history of a neurological condition
- Pregnancy (females)
- Claustrophobia
- Ferrous metallic implants or any surgically placed medical device not cleared for safety at 3Tesla MRI strength
- Positive Hepatitis C serology or other known viral infections that may induce insulin resistance
- Peripheral vascular disease
- Liver, kidney, or active blood disease
- Peripheral neuropathy
- Fasting glucose > 126 mg/dL
- Currently taking any medications that can alter glucose homeostasis (steroids, glucocorticoids, nicotinic acid)
- Currently taking thiazolidinediones or insulin
- Females currently on hormone replacement therapy (HRT) less than 6 months
- Being left handed
- Use of antidepressant medication within the past two weeks (six weeks fluoxetine)
- Suicide risk
- Current use of stimulants, antipsychotic medications, mood stabilizers, cognitive enhancers, statins, glucocorticoids, steroids, nicotinic acid, thiazolidinediones, insulin, metformin, any diabetes medications (e.g. gliptins), HIV medications.