Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Endogenous Opioid Mechanisms for Rejection Sensitivity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date July 11, 2014
First Posted Date July 15, 2014
Last Update Posted Date October 22, 2020
Study Start Date August 2016
Actual Primary Completion Date June 6, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 11, 2014)
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).
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: July 11, 2014)
  • 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).
  • 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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Endogenous Opioid Mechanisms for Rejection Sensitivity
Official Title Endogenous Opioid Mechanisms for Rejection Sensitivity
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.
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 Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
saliva, whole blood, blood plasma
Sampling Method Probability Sample
Study Population Healthy Controls
Condition Rejection Sensitivity
Intervention Not Provided
Study Groups/Cohorts Healthy Controls
Healthy men and women ages 18-25 years
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: October 19, 2020)
114
Original Estimated Enrollment
 (submitted: July 11, 2014)
96
Actual Study Completion Date June 6, 2019
Actual Primary Completion Date June 6, 2019   (Final data collection date for primary outcome measure)
Eligibility 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.)
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 25 Years   (Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02189785
Other Study ID Numbers R01MH102264( U.S. NIH Grant/Contract )
R01MH102264 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party David Hsu, Stony Brook University
Study Sponsor Stony Brook University
Collaborators
  • University of Michigan
  • National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: David T Hsu, Ph.D. Stony Brook University
PRS Account Stony Brook University
Verification Date October 2020