Endogenous Opioid Activity and Affective State in Insulin Resistant Women

Summary

Insulin resistance, a primary component of the metabolic syndrome, is an escalating phenomenon in the United States, and confers an increased risk of depression and mood disorder, particularly in women. The relationship between metabolic and mood disorders may be mediated by endogenous opioid activity in limbic brain regions. We propose to examine affective state and μ- opioid system function in insulin resistant women, and change in response to insulin sensitizing treatment, through the following specific aims and hypotheses:

Establish relationship between insulin resistance, affective state, and μ-opioid receptor function.

1. Insulin resistant women will have greater μ-opioid receptor availability at baseline, and a larger response to stress challenge than non-insulin resistant women
2. Insulin resistant women will have greater negative affective state at baseline, and a greater emotional response to stress challenge than non-insulin resistant women.
3. Mediational analyses will reveal that the relationship between insulin resistance and negative affect is mediated by μ-opioid receptor function and neural activation in the amygdala and nucleus accumbens affect-regulating regions.

Examine effects of insulin regulation on μ-opioid receptor function and affective state.

1. Improved insulin sensitivity will be accompanied by decreased μ-opioid receptor availability at baseline and a reduced response to stress challenge. Degree of change in baseline receptor availability and response to stress challenge after treatment will correlate with degree of insulin regulation.
2. Improved insulin sensitivity will be associated with improved affective state at baseline, and with a reduced emotional response to stress challenge. Degree of change in affective state and emotional response to stress challenge after treatment will correlate with degree of insulin regulation.
3. Mediational analyses will reveal that the change in affective state after insulin regulation is mediated by change in μ-opioid receptor function and neural activation in the amygdala and nucleus accumbens.

The expected results would suggest a role for the endogenous μ-opioid system in mediating the relationship between metabolic function and emotional processes.

Conditions

• Depression
• Insulin Resistance
• Metabolic Syndrome

Interventions

DRUG

Metformin

Women classified as insulin resistant will participate in both a placebo and a metformin treatment arm, each lasting about 16 weeks. Women will be randomized to order of treatment arms.

DRUG

Placebo

Placebo capsules prepared identically to Metformin capsules

Sponsors & Collaborators

• National Institute of Mental Health (NIMH)

  collaborator NIH

• University of Michigan

  lead OTHER

Principal Investigators

• Alison Berent-Spillson, PhD · University of Michigan

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-07-31

Primary Completion

2017-03-24

Completion

2017-09-30

Countries

• United States

Study Locations