Endogenous Opioid Mechanisms for Rejection Sensitivity
Condition: Rejection Sensitivity
MeSH terms: Hypersensitivity
Study type: Observational

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.
    

Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Healthy Controls
      
Biospecimen description: 
      saliva, whole blood, blood plasma
    
Keywords: social; rejection; acceptance; PET; opioid; fMRI; reward; exclusion