Brain Function in Depression and Insulin Resistance

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.