Endogenous Opioid Activity and Affective State in Insulin Resistant Women
Status:
Completed
Trial end date:
2017-09-01
Target enrollment:
Participant gender:
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.