Developmental Trajectories of Negative Symptoms in Schizophrenia

描述（由申请人提供）：Conte中心的目标是在人类和小鼠中探索精神分裂症的核心负面症状，情感表达能力和社会驱动力减弱的大脑回路。该中心将加强和扩大宾夕法尼亚大学精神分裂症研究中心，这是一个共同发现和基础设施的核心，旨在了解精神分裂症的神经基质。它利用该领域的新合作和进展，以多层次互补的方法追求转化目标，专注于解剖精神分裂症的主要表型特征，这些特征具有临床重要性，但人们对其知之甚少。主要目标包括：1。青春期负面症状和社交功能障碍与厌恶学习过程中杏仁核回路功能障碍的神经行为和神经生理指标的关系。2. 确定发育过程中杏仁核回路NMDAR1信号在社交情绪行为中的作用。3. 确定NMDAR1信号在体内杏仁核生理和社会行为中的作用。4. 描述患者死后杏仁核NMDA受体功能障碍与突触连接调节的关系。5. 研究NMDAR功能障碍的基因组基础及其与发育过程中受损情感和社会功能表型的关联。中心将有五个项目：1 .青少年厌恶学习和社交功能障碍的神经生理学；2。小鼠社交、情感行为和杏仁核功能的早期发育3。社会功能电生理标记；杏仁核NMDA受体功能低下；5 .精神分裂症NMDA受体通路的整合基因组分析。两个核心将支持项目：核心A管理和核心B数据和生物统计。该中心利用宾夕法尼亚大学研究人员的合作专业知识和资源进行这项具有挑战性的跨学科转化研究。除了推进其科学议程，该中心将成为教师，研究员，居民，研究生和本科生的教育资源。它也将是一个临床和教育。

DESCRIPTION (provided by applicant): The goal of the Conte Center is to probe brain circuitry that underlies the core negative symptoms of schizophrenia, diminished emotional expressivity and social drive, in humans and mice. The Center will enhance and expand the Penn Schizophrenia Research Center, a nucleus of joint discovery and infrastructure directed at understanding neural substrates of schizophrenia. It capitalizes on new collaborations and advances in the field, pursuing translational aims with multi-level complementary approaches focused on dissecting major phenotypic features of schizophrenia that are of clinical importance yet poorly understood. Major aims include: 1. Relate negative symptoms and social dysfunction in adolescence to neurobehavioral and neurophysiological measures of amygdala circuit dysfunction during aversive learning. 2. Determine the role of amygdala circuit NMDAR1 signaling in social-emotional behavior during development. 3. Determine the role of NMDAR1 signaling in amygdala physiology and social behavior in vivo. 4. Delineate NMDA receptor dysfunction in the postmortem amygdala of patients in relation to modulation of synaptic connectivity. 5. Investigate genomic underpinnings for NMDAR hypofunction and its association with phenotypes of impaired affective and social functioning during development. The Center will have five Projects: I. Neurophysiology of aversive learning and social dysfunction in youths; II. Early development of social and emotional behaviors and amygdala function in mice; III. Electrophysiological markers of social function; IV. NMDA receptor hypofunction in the amygdala; V. Integrative genomic analyses of NMDA receptor pathway in schizophrenia. Two Cores will support the Projects: Core A Administration and Core B Data and Biostatistics. The Center capitalizes on the collaborative expertise of investigators and resources at Penn for conducting this challenging interdisciplinary translational research. In addition to advancing its scientific agenda, the Center will be an educational resource for faculty, fellows, residents, graduate and undergraduate students. It will also be a clinical and educational.