Endogenous opioid mechanisms for rejection sensitivity

内源性阿片类药物排斥敏感性机制

• 批准号: 8755808
• 负责人: David Tai Hsu
• 金额: $ 45.55万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-19 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8755808
• 关键词: Age; Amygdaloid structure; Animals; Anterior; Anxiety; Area; Behavior; Behavioral; Binding; Brain; Canis familiaris; Child Abuse and Neglect; Chronic; Clinical; Cues; Depressed mood; Diagnostic and Statistical Manual of Mental Disorders; Disease; Distress; Eating; Emotional; Environmental Risk Factor; Feedback; Goals; Human; Hydrocortisone; Impulsivity; Insula of Reil; Investigation; Lead; Life Experience; Location; Measures; Mediating; Mental Depression; Mental disorders; Moods; Neurobiology; Neurosecretory Systems; Neurotransmitters; Opioid; Opioid Receptor; Outcome; Pain; Pathway interactions; Pattern; Personal Satisfaction; Personality; Personality Disorders; Plasma; Population; Positron-Emission Tomography; Psychologist; Rattus; Research; Research Project Grants; Rest; Rewards; Risk Factors; Role; Social Behavior; Social Environment; System; Testing; Thalamic structure; Variant; Ventral Striatum; Withdrawal; behavioral response; blood pressure reduction; density; depressive symptoms; endogenous opioids; experience; high risk; in vivo; midbrain central gray substance; neurotransmission; postsynaptic; presynaptic; public health relevance; receptor; social; social anxiety; trait; young adult

DESCRIPTION (provided by applicant): 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 ¿-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.

描述（由申请人提供）：人类依赖于被接纳为群体和亲密关系来生存和情感幸福。对这种需求的实际或感知威胁，如社会排斥（当一个人不被需要或喜欢时），会导致情绪和行为的明显变化，如悲伤，社交退缩和冲动。在那些对拒绝敏感的人中，严重或反复的社会拒绝经历是导致 精神障碍，如重度抑郁症、社交焦虑症和人格障碍。排斥敏感性（RS）的神经递质机制尚不清楚。在非人类动物中，内源性阿片系统，特别是莫尔受体（MOR）系统，调节社会痛苦和社会奖励行为已有30多年的历史。最近，我们利用正电子发射断层扫描技术发现，社会排斥和接受在特定的大脑区域产生了强大的莫尔介导的神经传递，这与情绪和行为的变化有关。这项研究首次表明，内源性阿片系统对人类的社会线索作出反应。拟议项目将检查RS临床重要特征的莫尔系统。由于RS的神经递质机制是未知的，我们试图首先了解RS在健康人群中的基本神经生物学，然后再研究临床人群。总体假设是RS与莫尔功能相关。与较低RS相比，具有较高RS的人被假设在社会拒绝和接受期间具有总体较低的莫尔激活，导致更大的痛苦和抑制的亲社会行为。许多动物研究也证实，莫尔系统受到有害社会环境的强烈影响。因此，我们还将研究儿童期虐待（CM）的作用，这是一种负面的早期生活经历，已知是发展抑郁和焦虑的最高风险因素之一。本项目的目标是确定RS和CM如何相互作用，以确定健康人群中基线、社会排斥和社会接受期间的莫尔结合模式。我们还将研究如何RS，介导的莫尔激活，影响情绪和行为。这项研究的影响是为理解RS的神经递质机制迈出了重要的第一步，其长期目标是预测和治疗其相关疾病。