Social affiliation in psychosis: Mechanisms and vulnerability factors

 描述（由申请人提供）：人类有一个基本的“需要归属。“我们有很强的动力去寻找、参与和保持强烈的人际依恋。然而，对许多精神疾病患者来说，发展和保持亲密关系并不是一件容易的事。社会动机的紊乱尤其令人衰弱， 昂贵，在精神病相关精神病理学（PRP）患者中了解甚少。RDoC的关系结构提供了一个基础，概念化和解包的机制，这些干扰的社会动机。我们的科学目标是将RDoC关联结构划分为两个独立的子过程。具体来说，我们将研究大脑的社交方式和回避动机系统如何与PRP患者的社交障碍相关，并在未受影响的兄弟姐妹中受到影响。本研究以社会神经科学中的关系转化模型为基础，该模型包括两个不同的神经子系统：（1）社会接近动机系统对社会安全信号敏感，并促进社会参与和依恋（主要涉及纹状体、腹内侧额叶皮质和下丘脑）;（2）社交回避动机系统对社交威胁信号敏感，并促进避免拒绝和不和谐（主要涉及前扣带回，前扣带回和杏仁核）。这些系统由选择的神经肽/递质调节，主要是催产素（OXT），加压素（AVP），多巴胺和阿片类药物。来自我们实验室和其他实验室的数据表明，联系中的问题可能源于PRP中这两个系统的干扰。我们预测，社会的做法和回避作出独立的贡献，虽然可分离的神经行为机制，精神病的社会功能受损。此外，我们将在未受影响的兄弟姐妹中评估这些系统，以确定它们是否反映了社会残疾和精神病的脆弱性因素（不受药物和慢性病的混淆）。80名有临床显著精神病症状史的门诊患者、80名未受影响的兄弟姐妹和40名来自社区的健康个体的多样化样本将在四个RDoC分析单位完成既定测量：电路（两个社会奖励/惩罚fMRI任务），生理学（N170对批准/威胁面孔的反应），行为（社会奖励/惩罚学习任务）和自我报告（归属感需要，拒绝恐惧量表）以及社会功能评估。一个探索性的目的是检查OXT/AVP分子和受体基因多态性是否与四个分析单位的个体差异有关。我们的主要假设检验（1） 社会接近和回避动机结构在多个分析单元中的有效性及其对解释真实的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会接近/回避的障碍，表现出显着的家庭内相关性。对导致社会关系问题的神经过程的机械理解对于开发新的以恢复为导向的预防性治疗至关重要。

 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.