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.

Study Overview

• Status: Terminated
• Conditions: Depression; Insulin Resistance
• Intervention / Treatment: Behavioral: Gambling Task

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Western Psychiatric Institute and Clinic at University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metabolically Healthy - Non-depressed; Overweight individuals without metabolic syndrome and free of psychiatric illness	Behavioral: Gambling Task
Experimental: Metabolically Healthy - Depressed; Overweight individuals without metabolic syndrome and with active major depression	Behavioral: Gambling Task
Experimental: Insulin Resistant - Depressed; Overweight individuals with metabolic syndrome and active major depression	Behavioral: Gambling Task
Experimental: Insulin Resistant - Non-depressed; Overweight individuals with metabolic syndrome and free of psychiatric illness	Behavioral: Gambling Task

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fMRI BOLD Response in Striatal Regions	The investigators will monitor the blood oxygen level dependent response using fMRI and compare activation during "win" trials vs. "loss" trials	During Gambling Task in fMRI Scanner

Collaborators and Investigators

• Sponsor: University of Pittsburgh

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: August 23, 2016
• First Submitted That Met QC Criteria: September 2, 2016
• First Posted (Estimate): September 5, 2016

Study Record Updates

• Last Update Posted (Actual): December 5, 2017
• Last Update Submitted That Met QC Criteria: December 2, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Glucose Metabolism Disorders; Metabolic Diseases; Mood Disorders; Hyperinsulinism; Depression; Depressive Disorder; Insulin Resistance
• Other Study ID Numbers: 16060315

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO