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Endogenous Opioid Mechanisms for Rejection Sensitivity

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ClinicalTrials.gov Identifier: NCT02189785
Recruitment Status : Completed
First Posted : July 15, 2014
Last Update Posted : October 22, 2020
Sponsor:
Collaborators:
University of Michigan
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
David Hsu, Stony Brook University

Study Description
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Brief Summary:
This project hypothesizes that the brain's opioid system determines rejection sensitivity, a personality trait that is a vulnerability factor and feature of several psychiatric disorders. This project will use positron emission tomography to measure the brain's opioid response to social rejection and acceptance in a nonclinical population with varying levels of rejection sensitivity. The results will provide the first major step towards understanding a neurotransmitter mechanism for rejection sensitivity, allowing for further investigation into predicting and treating its associated disorders.

Condition or disease
Rejection Sensitivity

Detailed Description:

Humans depend on acceptance into groups and intimate relationships for survival and emotional well-being. Actual or perceived threats to this need such as social rejection (when one is not wanted or liked) can lead to marked changes in mood and behavior such as sadness, social withdrawal, and impulsivity. The experience of severe or repeated social rejection in those who are rejection sensitive is a strong contributor to psychiatric disorders such as major depressive, social anxiety, and personality disorders. The neurotransmitter mechanisms underlying rejection sensitivity (RS) are not known.

It has been known for over 30 years in nonhuman animals that the endogenous opioid system, particularly the µ-opioid receptor (MOR) system, regulates social distress and social reward behaviors. Using positron emission tomography, we recently showed that social rejection and acceptance produced robust MOR-mediated neurotransmission in specific brain areas, which correlated with changes in mood and behavior. This study was the first to show that the endogenous opioid system responds to social cues in humans. The proposed project will examine the MOR system in the clinically important trait of RS. Since the neurotransmitter mechanisms of RS are unknown, we seek to first understand the basic neurobiology of RS in a healthy population, prior to studying clinical populations.

The overall hypothesis is that RS is associated with MOR function. Those with higher RS compared to lower RS are hypothesized to have overall lower MOR activation during social rejection and acceptance, leading to greater distress and dampened pro-social behavior. Numerous animal studies have also established that the MOR system is strongly influenced by harmful social environments. Therefore, we will also examine the role of childhood maltreatment (CM), a negative early life experience known to be one of the highest risk factors for developing depression and anxiety. The goal of this project is to determine how RS and CM interact to determine patterns of MOR binding during baseline, social rejection, and social acceptance in a healthy population. We will also examine how RS, mediated through MOR activation, influences mood and behavior.

The impact of this research is to provide the first major step towards understanding a neurotransmitter mechanism for RS, with the long-term goal of predicting and treating its associated disorders.

Study Design
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Study Type : Observational
Actual Enrollment : 114 participants
Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: Endogenous Opioid Mechanisms for Rejection Sensitivity
Study Start Date : August 2016
Actual Primary Completion Date : June 6, 2019
Actual Study Completion Date : June 6, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy

Groups and Cohorts
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Group/Cohort
Healthy Controls
Healthy men and women ages 18-25 years


Outcome Measures
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Primary Outcome Measures :
  1. Mu-opioid binding potential [ Time Frame: within 30 days of informed consent ]
    This study will measure levels of radiotracer (carbon-11-labeled carfentanil) binding to the mu-opioid receptor in the brain using positron-emission tomography (PET). Primary regions of interest include: the amygdala, anterior insular cortex, anterior cingulate cortex, nucleus accumbens, and thalamus. All structures will be examined bilaterally. Differences in binding potential (Bmax/Kd) for the radiotracer will be compared across different experimental conditions (e.g., neutral, positive, negative social feedback).


Secondary Outcome Measures :
  1. fMRI blood-oxygen-level-dependent (BOLD) response [ Time Frame: within 30 days of informed consent ]
    This study will measure brain activation in response to social feedback and monetary reward. Primary regions of interest include: the amygdala, anterior insular cortex, and the nucleus accumbens. All structures will be examined bilaterally. Arbitrary units for fMRI BOLD are used to compare activation during one condition (e.g., neutral, baseline) vs. another condition (e.g., positive social feedback, monetary reward).

  2. Plasma cortisol [ Time Frame: within 30 days of informed consent ]
    This study will collect blood every 10 minutes during PET to measure changes in levels of plasma cortisol. Units are ug/dL.


Biospecimen Retention:   Samples With DNA
saliva, whole blood, blood plasma

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 25 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Healthy Controls
Criteria

Inclusion Criteria:

  • Men and women age 18-25 (inclusive)
  • Right-handed
  • Native English speaker
  • Not currently in a romantic relationship
  • Willing and able to participate in a PET scan

Exclusion Criteria:

  • Not on hormonal birth control
  • Not pregnant
  • Consume less than 5 cigarettes per week and less than 14 alcoholic drinks per week, on average
  • No use of recreational or street drugs in the past two years (e.g. marijuana)
  • Willing to abstain from alcohol and/or tobacco for 48 hours
  • No major untreated medical problems
  • Never diagnosed with a psychiatric or neurological disorder
  • Potential problems with having an MRI scan (claustrophobia, metal objects, etc.)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02189785


Locations
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United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
Stony Brook University
University of Michigan
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: David T Hsu, Ph.D. Stony Brook University
More Information
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Responsible Party: David Hsu, Assistant Professor, Stony Brook University
ClinicalTrials.gov Identifier: NCT02189785    
Other Study ID Numbers: R01MH102264 ( U.S. NIH Grant/Contract )
R01MH102264 ( U.S. NIH Grant/Contract )
First Posted: July 15, 2014    Key Record Dates
Last Update Posted: October 22, 2020
Last Verified: October 2020
Keywords provided by David Hsu, Stony Brook University:
social
rejection
acceptance
PET
 opioid
fMRI
reward
exclusion
Additional relevant MeSH terms:
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Hypersensitivity
Immune System Diseases