Social affiliation in psychosis: Mechanisms and vulnerability factors

精神病的社会归属：机制和脆弱性因素

基本信息

批准号：
8942485
负责人：
WILLIAM P. HORAN
金额：
$ 48.33万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-17 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8942485
关键词：
Accounting Agreement Alleles Amygdaloid structure Anhedonia Anterior Blood Blood specimen Brain Clinical Communities Corpus striatum structure Data Development Dopamine Face Factor Analysis Family Family history of Foundations Fright Functional Magnetic Resonance Imaging Functional disorder Genetic Polymorphism Genomics Goals Hippocampus (Brain)Human Hypothalamic structure Impairment Individual Individual Differences Insula of Reil Intervention Lead Learning Life Link Measures Mental disorders Modeling Motivation Neuropeptide Gene Neuropeptides Opioid Outpatients Oxytocin Oxytocin Receptor Participant Pathway interactions Patient Self-Report Performance Pharmaceutical Preparations Physiology Process Psyche structure Psychological reinforcement Psychopathology Psychotic Disorders Publishing Punishment Receptor Gene Recording of previous events Recovery Research Domain Criteria Rewards Safety Sampling Siblings Signal Transduction Social Behavior Social Functioning Solutions Source Structure Symptoms System Testing Vasopressins Ventral Tegmental Area base clinically significant disability frontal lobe member neurobehavioral physical conditioning proband psychologic psychotic symptoms public health relevance relating to nervous system response satisfaction self reported behavior social social neuroscience stem trait

项目摘要

DESCRIPTION (provided by applicant): Human beings have a fundamental "need to belong." We are powerfully motivated to seek out, engage in, and maintain strong interpersonal attachments. Developing and maintaining close relationships, however, is not an easy task for many people with mental illnesses. Disturbances in social motivation are particularly debilitating, costly, and poorly understood in people with psychosis-related psychopathology (PRP). The RDoC affiliation construct provides a foundation for conceptualizing and unpacking the mechanisms of these disturbances in social motivation. Our scientific goal is to carve the RDoC affiliation construct into two separate sub-processes. Specifically, we will examine how the social approach and avoidance motivation systems of the brain relate to social disability across individuals with PRP and are impacted in their unaffected siblings. This project is grounded in a translational social neuroscience model of affiliation that includes two distinct neural sub-systems: (1) the social approach motivation system is sensitive to social safety signals and promotes social engagement and attachment (primarily involving the striatum, ventromedial frontal cortex, and hypothalamus); (2) the social avoidance motivation system is sensitive to social threat signals and promotes avoidance of rejection and discord (primarily involving the insula, anterior cingulate, and amygdala). These systems are modulated by select neuropeptides/transmitters, chiefly oxytocin (OXT), vasopressin (AVP), dopamine, and opioids. Data from our lab and others indicate that problems in affiliation can stem from disturbances in both of these systems across PRP. We predict that social approach and avoidance make independent contributions, though separable neurobehavioral mechanisms, to impaired social functioning in psychosis. In addition, we will evaluate these systems in unaffected siblings to determine whether they reflect vulnerability factors for social disability and psychosis (unconfounded by medication and chronicity). A diverse sample of 80 outpatients with a history of clinically significant psychotic symptoms, 80 of their unaffected siblings, and 40 healthy individuals from the community will complete established measures at four RDoC units of analysis: circuits (two social reward/punishment fMRI tasks), physiology (N170 responses to approving/ threatening faces), behavior (social reward/punishment learning task), and self-report (need for belonging, fear of rejection scales), as well as social functioning assessments. An exploratory aim will examine whether OXT/AVP molecule and receptor gene polymorphisms relate to individual differences across the four units of analysis. Our primary hypotheses test (1) the validity of the social approach and avoidance motivation constructs across multiple units of analyses and their predictive validity for explaining real world social functioning, and (2) whethe unaffected siblings show impairments in social approach/ avoidance that demonstrate significant within-family correlations. A mechanistic understanding of neural processes that lead to problems in social affiliation is essential for developing new recovery-oriented and preventative treatments.

描述（由申请人提供）：人类具有基本的“需要属于。人际交往。但是，对于患有精神疾病的商店者来说，发展和维持密切的关系并不是一件容易的事。昂贵的人在与精神病相关的精神病患者中（PRP）。同胞。和假设）;阿片类药物。我们实验室的数据和其他指示可以在PRP的两个系统中脱颖而出。）。（需要归属，拒绝量表），以及社会功能评估和受体基因多态性。社会和跨越多个单位的ofalysess和thedive of Alysess和Thedive的有效性，以实现现实世界的社会功能，（2）在社会方法/回避中未受到影响的兄弟姐妹，这表明了与家庭相关性的机械理解。在社会隶属关系中，对于开发新的面向恢复和预防性的环境至关重要。