Social affiliation in psychosis: Mechanisms and vulnerability factors

精神病的社会归属：机制和脆弱性因素

• 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
• 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

 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）：人类有一种基本的“归属感”。我们有强烈的动机去寻找、参与和维持牢固的人际依恋，然而，对许多人来说，发展和维持亲密关系并不是一件容易的事。患有精神疾病的人尤其会感到衰弱， RDoC 隶属结构为概念化和解析这些社会动机障碍的机制提供了基础，而且对精神病相关精神病理学 (PRP) 患者的了解甚少。具体来说，我们将研究大脑的社交方法和回避动机系统如何与 PRP 患者的社交障碍相关，以及如何影响他们未受影响的兄弟姐妹。该项目基于转化社会神经科学模型。归属感包括两个不同的神经子系统：（1）社交接近动机系统对社交安全信号敏感，促进社交参与和依恋（主要涉及纹状体、腹内侧额叶皮层和下丘脑）；回避动机系统对社会威胁信号敏感，并促进避免拒绝和不和谐（主要涉及岛叶、前扣带回和杏仁核）。这些系统受到选择的调节。我们实验室和其他实验室的数据表明，归属问题可能源于 PRP 中这两个系统的干扰。通过可分离的神经行为机制，对精神病中的社会功能受损做出独立的贡献。此外，我们将评估未受影响的兄弟姐妹的这些系统，以确定它们是否反映了社交障碍和社会功能障碍的脆弱性因素。精神病（不受药物和慢性病困扰）的不同样本，包括 80 名有临床显着精神病症状史的门诊患者、80 名未受影响的兄弟姐妹以及来自社区的 40 名健康个体，将完成四个 RDoC 分析单元的既定测量：电路（两项社会奖励/惩罚功能磁共振成像任务）、生理学（N170 对认可/威胁面孔的反应）、行为（社会奖励/惩罚学习任务）和自我报告（归属感、拒绝恐惧量表）以及社会功能评估将检查 OXT/AVP 分子和受体基因多态性是否与我们的四个分析单元的个体差异相关 (1)。 跨多个分析单元的社交接近和回避动机结构的有效性及其解释现实世界社会功能的预测有效性，以及（2）未受影响的兄弟姐妹是否表现出社交接近/回避的障碍，从而表明对家庭内部相关性的理解存在显着的障碍。导致社会归属问题的神经过程对于开发新的以恢复为导向的预防性治疗至关重要。