<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02189785</url>
  </required_header>
  <id_info>
    <org_study_id>R01MH102264</org_study_id>
    <secondary_id>R01MH102264</secondary_id>
    <nct_id>NCT02189785</nct_id>
  </id_info>
  <brief_title>Endogenous Opioid Mechanisms for Rejection Sensitivity</brief_title>
  <official_title>Endogenous Opioid Mechanisms for Rejection Sensitivity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stony Brook University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Stony Brook University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This project hypothesizes that the brain's opioid system determines rejection sensitivity, a&#xD;
      personality trait that is a vulnerability factor and feature of several psychiatric&#xD;
      disorders. This project will use positron emission tomography to measure the brain's opioid&#xD;
      response to social rejection and acceptance in a nonclinical population with varying levels&#xD;
      of rejection sensitivity. The results will provide the first major step towards understanding&#xD;
      a neurotransmitter mechanism for rejection sensitivity, allowing for further investigation&#xD;
      into predicting and treating its associated disorders.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Humans depend on acceptance into groups and intimate relationships for survival and emotional&#xD;
      well-being. Actual or perceived threats to this need such as social rejection (when one is&#xD;
      not wanted or liked) can lead to marked changes in mood and behavior such as sadness, social&#xD;
      withdrawal, and impulsivity. The experience of severe or repeated social rejection in those&#xD;
      who are rejection sensitive is a strong contributor to psychiatric disorders such as major&#xD;
      depressive, social anxiety, and personality disorders. The neurotransmitter mechanisms&#xD;
      underlying rejection sensitivity (RS) are not known.&#xD;
&#xD;
      It has been known for over 30 years in nonhuman animals that the endogenous opioid system,&#xD;
      particularly the µ-opioid receptor (MOR) system, regulates social distress and social reward&#xD;
      behaviors. Using positron emission tomography, we recently showed that social rejection and&#xD;
      acceptance produced robust MOR-mediated neurotransmission in specific brain areas, which&#xD;
      correlated with changes in mood and behavior. This study was the first to show that the&#xD;
      endogenous opioid system responds to social cues in humans. The proposed project will examine&#xD;
      the MOR system in the clinically important trait of RS. Since the neurotransmitter mechanisms&#xD;
      of RS are unknown, we seek to first understand the basic neurobiology of RS in a healthy&#xD;
      population, prior to studying clinical populations.&#xD;
&#xD;
      The overall hypothesis is that RS is associated with MOR function. Those with higher RS&#xD;
      compared to lower RS are hypothesized to have overall lower MOR activation during social&#xD;
      rejection and acceptance, leading to greater distress and dampened pro-social behavior.&#xD;
      Numerous animal studies have also established that the MOR system is strongly influenced by&#xD;
      harmful social environments. Therefore, we will also examine the role of childhood&#xD;
      maltreatment (CM), a negative early life experience known to be one of the highest risk&#xD;
      factors for developing depression and anxiety. The goal of this project is to determine how&#xD;
      RS and CM interact to determine patterns of MOR binding during baseline, social rejection,&#xD;
      and social acceptance in a healthy population. We will also examine how RS, mediated through&#xD;
      MOR activation, influences mood and behavior.&#xD;
&#xD;
      The impact of this research is to provide the first major step towards understanding a&#xD;
      neurotransmitter mechanism for RS, with the long-term goal of predicting and treating its&#xD;
      associated disorders.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2016</start_date>
  <completion_date type="Actual">June 6, 2019</completion_date>
  <primary_completion_date type="Actual">June 6, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Mu-opioid binding potential</measure>
    <time_frame>within 30 days of informed consent</time_frame>
    <description>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).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>fMRI blood-oxygen-level-dependent (BOLD) response</measure>
    <time_frame>within 30 days of informed consent</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma cortisol</measure>
    <time_frame>within 30 days of informed consent</time_frame>
    <description>This study will collect blood every 10 minutes during PET to measure changes in levels of plasma cortisol. Units are ug/dL.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">114</enrollment>
  <condition>Rejection Sensitivity</condition>
  <arm_group>
    <arm_group_label>Healthy Controls</arm_group_label>
    <description>Healthy men and women ages 18-25 years</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      saliva, whole blood, blood plasma&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Healthy Controls&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women age 18-25 (inclusive)&#xD;
&#xD;
          -  Right-handed&#xD;
&#xD;
          -  Native English speaker&#xD;
&#xD;
          -  Not currently in a romantic relationship&#xD;
&#xD;
          -  Willing and able to participate in a PET scan&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not on hormonal birth control&#xD;
&#xD;
          -  Not pregnant&#xD;
&#xD;
          -  Consume less than 5 cigarettes per week and less than 14 alcoholic drinks per week, on&#xD;
             average&#xD;
&#xD;
          -  No use of recreational or street drugs in the past two years (e.g. marijuana)&#xD;
&#xD;
          -  Willing to abstain from alcohol and/or tobacco for 48 hours&#xD;
&#xD;
          -  No major untreated medical problems&#xD;
&#xD;
          -  Never diagnosed with a psychiatric or neurological disorder&#xD;
&#xD;
          -  Potential problems with having an MRI scan (claustrophobia, metal objects, etc.)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David T Hsu, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stony Brook University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>July 11, 2014</study_first_submitted>
  <study_first_submitted_qc>July 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 15, 2014</study_first_posted>
  <last_update_submitted>October 19, 2020</last_update_submitted>
  <last_update_submitted_qc>October 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stony Brook University</investigator_affiliation>
    <investigator_full_name>David Hsu</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>social</keyword>
  <keyword>rejection</keyword>
  <keyword>acceptance</keyword>
  <keyword>PET</keyword>
  <keyword>opioid</keyword>
  <keyword>fMRI</keyword>
  <keyword>reward</keyword>
  <keyword>exclusion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02189785
org study id: R01MH102264
secondary id: R01MH102264
nct id: NCT02189785
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
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.
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.
observational model: Case-Only
time perspective: Cross-Sectional
measure: Mu-opioid binding potential
time frame: within 30 days of informed consent
description: 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).
measure: fMRI blood-oxygen-level-dependent (BOLD) response
time frame: within 30 days of informed consent
description: 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).
measure: Plasma cortisol
time frame: within 30 days of informed consent
description: This study will collect blood every 10 minutes during PET to measure changes in levels of plasma cortisol. Units are ug/dL.
arm group label: Healthy Controls
description: Healthy men and women ages 18-25 years
saliva, whole blood, blood plasma
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 25 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David T Hsu, Ph.D.
role: Principal Investigator
affiliation: Stony Brook University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Stony Brook University
investigator full name: David Hsu
investigator title: Assistant Professor
mesh term: Hypersensitivity