Brain Function in Depression and Insulin Resistance

The purpose of this study is to help researchers learn about how the brain responds to rewards. This study is interested in seeing how these responses differ between people who are more and less responsive to insulin in their body, and people with and without depression.

The investigators will monitor the blood oxygen level dependent response using fMRI and compare activation during "win" trials vs. "loss" trials

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.