Endogenous Opioid Activity and Affective State in Insulin Resistant Women
| Status: | Completed |
|---|---|
| Conditions: | Depression, Depression, Endocrine, Endocrine |
| Therapuetic Areas: | Endocrinology, Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 40 |
| Updated: | 11/10/2018 |
| Start Date: | July 2014 |
| End Date: | September 2017 |
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.
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.
The objective of this study is to examine the role of the endogenous mu-opioid system in
mediating the relationship between metabolic dysfunction and depressive symptoms in
reproductive aged women.
PET image data was unable to be analyzed due to PET equipment replacement midway through
study, leaving PET images collected at beginning of study incompatible with PET images
collected later in study.
Due to insufficient enrollment in treatment arms, the 20 or 40 week data was unusable for
analytic goals, so the study was re-framed for what could usefully be learned about baseline
characteristics among the study populations and the originally planned outcome measures were
amended to only to those that related to understanding the baseline population.
mediating the relationship between metabolic dysfunction and depressive symptoms in
reproductive aged women.
PET image data was unable to be analyzed due to PET equipment replacement midway through
study, leaving PET images collected at beginning of study incompatible with PET images
collected later in study.
Due to insufficient enrollment in treatment arms, the 20 or 40 week data was unusable for
analytic goals, so the study was re-framed for what could usefully be learned about baseline
characteristics among the study populations and the originally planned outcome measures were
amended to only to those that related to understanding the baseline population.
Inclusion Criteria:
- Women
- 18-40 years old
- metabolically healthy or insulin resistant (insulin sensitivity > 1.89x10-4 (min-1 x
µU-1 x mL-1; calculated by minimal model assessment of glucose tolerance test)
- body mass index (BMI = weight (kg) / height2 (m2)) between 18 kg/m2 and 35 kg/m2.
- Women with mild or moderate depressive symptoms not meeting the criteria for Major
Depressive Disorder will be included.
Exclusion Criteria:
- men
- left handed
- acute medical illness
- uncorrected thyroid disease
- diabetes (fasting glucose ≥126 mg/dL)\
- neurological disease
- major depression
- substance abuse
- MRI contraindications (claustrophobia, pacemakers, pumps, metallic agents or devices)
- severe calorie restriction
- intense physical exercise ≥1 hour/day
- smoking within 6 months
- hormonal, insulin sensitizing, or centrally acting medications within 2 months
- pregnancy within 6 months
- lactation
- cardiac or pulmonary insufficiency
- liver or renal insufficiency (>2.5 x normal transaminases levels, plasma creatinine
≥1.4 mg/dL)
- history of lactic acidosis
- BMI ≥35 kg/m2
- opioid allergy
We found this trial at
1
site
Ann Arbor, Michigan 48109
Principal Investigator: Alison Berent-Spillson, PhD
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