Social Withdrawal Following Trauma Exposure: a Neuroeconomic Approach

创伤暴露后的社交退缩：神经经济学方法

• 批准号: 9769142
• 负责人: ELIZABETH OLSON
• 金额: $ 16.91万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-14 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769142
• 关键词: Anhedonia; Anxiety Disorders; Area; Award; Behavior; Behavioral; Brain; Consultations; Control Groups; Corpus striatum structure; Data; Data Analyses; Development; Dimensions; Disease; Doctor of Medicine; Doctor of Philosophy; Dorsal; Exposure to; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Health; Hospitals; Human; Immune response; Impairment; Incidence; Individual; Investments; Lead; Learning; Link; Medial; Mediating; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentorship; Methodology; Mission; Modeling; Molecular Target; Mood Disorders; National Institute of Mental Health; Neurobiology; Neuroendocrinology; Neurophysiology - biologic function; Outcome; Ovarian hormone; Pathway interactions; Patient Self-Report; Peptides; Phase; Population; Positioning Attribute; Post-Traumatic Stress Disorders; Prefrontal Cortex; Research; Research Activity; Research Design; Research Institute; Rewards; Risk; Signal Transduction; Social Behavior; Social Functioning; Social Interaction; Social Network; Stress; Suicide; Symptoms; Training; Training Activity; Training Programs; Trauma; Trust; Ventral Striatum; Virginia; Withdrawal; Woman; Work; affective neuroscience; behavioral outcome; biological adaptation to stress; biomarker identification; clinical development; clinically relevant; cost; design; disability; experience; independency; innovation; medical schools; molecular marker; mortality risk; neurobehavioral; neurobiological mechanism; neurochemistry; neuroeconomics; neuroimaging; neuromechanism; neurotransmission; pituitary adenylate cyclase activating polypeptide; potential biomarker; predictive marker; programs; psychiatric symptom; relating to nervous system; response; reward circuitry; social; social deficits; social integration; stress related disorder; suicidal risk; translational neuroscience; trauma exposure

Project Summary/Abstract Impaired social functioning is a frequent and disabling consequence of trauma-related disorders. Although social withdrawal results in widespread disability in trauma-exposed populations, little is known about the neurobiological mechanisms underlying this dysfunction. In this project, social withdrawal following trauma exposure is conceptualized as resulting from dysregulation within brain reward pathways. The applicant proposes to use a neuroeconomic paradigm, the Trust Task, to probe alterations in social reward functioning in trauma-exposed populations. Possible contributions of a stress peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), implicated in changes in social behavior following stress exposure, will be identified. The central hypothesis is that in trauma-exposed populations, the extent of social withdrawal (decreased social network size) will be predicted by alterations in both Trust Task behavior and abnormal reward-related neural signaling in the ventral striatum, dorsal striatum, and medial prefrontal cortex. This Mentored Patient-Oriented Research Career Development Award combines research and training activities to support the applicant's long-range goal of developing an independent research program applying neuroeconomic paradigms within dimensional models of anxiety and mood disorders. The first training aim is to develop the applicant's expertise in research on trauma and PTSD. This will be supported through intensive mentorship, provided by Isabelle Rosso, Ph.D., an expert on PTSD neurochemistry, and Kerry Ressler, M.D., Ph.D., an expert in the translational neuroscience of PTSD, both of McLean Hospital/ Harvard Medical School (HMS). The second training aim is to develop expertise in fMRI paradigm design and analysis of neuroeconomic data. This will be supported via mentorship by Diego Pizzagalli, Ph.D., an expert in affective neuroscience, and through consultation with Blaise Frederick, Ph.D., an expert on fMRI, both at McLean Hospital/ HMS, as well as through consultation with Read Montague, Ph.D., a neuroeconomics expert at Virginia Tech Carilion Research Institute. The third training aim is to develop expertise in stress neuroendocrinology, including stress peptides and their interactions with ovarian hormones. This aim will be supported by Dr. Ressler, who originally identified the relationship between PACAP and PTSD in humans. The program of training has been carefully planned to position the applicant for research independency by the end of the award period. The contribution of the proposed research will advance the field by identifying behavioral, neural, and molecular biomarkers for social anhedonia and social withdrawal in trauma-exposed women. By using neuroeconomic paradigms to characterize alterations in reward circuitry that contribute to social withdrawal, the proposed research represents a substantive departure from the status quo. To summarize, the proposed project will provide the applicant with a strong foundation in PTSD research and functional neuroimaging, while also advancing understanding of the neural mechanisms underlying social withdrawal following trauma exposure.

项目总结/摘要 社会功能受损是创伤相关疾病的常见和致残后果。虽然 社会退缩导致创伤暴露人群中广泛的残疾，但对创伤暴露人群的社会退缩知之甚少。 这种功能障碍的神经生物学机制。在这个项目中，创伤后的社会退缩 暴露被概念化为大脑奖赏途径内的调节失调的结果。申请人 建议使用神经经济学范式，信任任务，探索社会奖励功能的改变， 创伤暴露人群。一种应激肽，垂体腺苷酸环化酶激活肽 多肽（PACAP），牵连在社会行为的变化后，压力暴露，将被确定。的 中心假设是，在创伤暴露人群中，社会退缩的程度（社会退缩减少）， 网络大小）将通过信任任务行为和异常奖励相关神经元的改变来预测 腹侧纹状体、背侧纹状体和内侧前额叶皮质的信号。以患者为导向的指导 研究职业发展奖结合了研究和培训活动，以支持申请人的 长期目标是开发一个独立的研究计划，在其中应用神经经济学范式。 焦虑和情绪障碍的三维模型。第一个培训目标是发展申请人的专业知识 创伤和创伤后应激障碍的研究这将通过Isabelle提供的密集辅导予以支持 罗索博士，创伤后应激障碍神经化学方面的专家，以及医学博士Kerry Ressler，哲学博士、的专家 创伤后应激障碍的转化神经科学，姆克林医院/哈佛医学院（HMS）。第二 培训目标是发展功能磁共振成像范例设计和神经经济学数据分析的专业知识。这将是 通过Diego Pizzagalli博士的指导支持，情感神经科学专家， 咨询布莱斯·弗雷德里克博士，一位功能磁共振成像专家，在姆克林医院/ HMS，以及 通过咨询Read Montague博士，弗吉尼亚理工大学神经经济学专家 院第三个培训目标是培养应激神经内分泌学方面的专业知识，包括应激肽 以及它们与卵巢激素的相互作用。这一目标将得到雷斯勒博士的支持，他最初 确定了人类PACAP和PTSD之间的关系。训练计划经过了仔细的 计划在奖励期结束前将申请人定位为研究独立性。的贡献 拟议的研究将通过确定行为，神经和分子生物标志物来推进该领域， 社会快感缺乏和社会退缩在创伤暴露妇女。通过使用神经经济学范式， 描述了奖励回路的变化，有助于社会退缩，拟议的研究， 代表着对现状的实质性偏离。总而言之，拟议项目将提供 申请人在创伤后应激障碍研究和功能性神经影像学方面有着坚实的基础，同时也在推进 了解创伤暴露后社会退缩的神经机制。