The Conte Center for Schizophrenia Research

描述(由申请人提供)：这是一份新的康特精神分裂症研究中心的申请，总部设在纽约大学医学院(NYUSoM)和附属的内森·克莱恩精神病学研究所(NKI)。精神分裂症(SZ)与感觉加工缺陷有关，这是该疾病的核心但未被研究的组成部分。在听觉系统中，患者在音调匹配和听觉失配负波(MMN)生成等基本过程中表现出缺陷。在视觉系统中，患者在对比度增强和整合等过程中表现出缺陷，这导致了物体识别和人脸识别等过程中的高阶损伤。感觉缺陷可能与N-甲基-2-甲基-D-天冬氨酸的损伤有关。 D-天冬氨酸(NMDA)受体介导的神经传递，特别是 使用人类和动物模型进行翻译研究。该中心由6个项目和3个核心组成，它们建立在中心调查人员之间先前存在的合作基础上。项目1、2和4以NKI/NYSoM为基础，利用人类(Javitt)和灵长类(Schroeder)神经生理学以及人类死后/激光捕获显微镜/基因阵列(Ginsberg/Smiley)方法研究SZ感觉皮质功能障碍和功能连接受损。项目3(Hlllyard)以加州大学圣迭戈分校为基础，研究正常视觉功能背后的调制过程。项目5(康布拉特)以Zucker Hillside医院为基础，研究SZ前驱症状中的感觉处理功能障碍。最后，项目6(Weiser)设在Sheba医院/特拉维夫大学，评估肌氨酸(N-甲基甘氨酸)的有效性，肌氨酸是一种自然产生的NMDA激动剂，目前在美国还没有。核心专门用于管理(Javitt)、患者招募/评估(Butler)和数据管理/生物统计(Robinson/Petkova)。虽然传统的SZ模型侧重于多巴胺，但较新的模型侧重于潜在的谷氨酸能功能障碍，并得到了神经遗传学、成像和治疗研究的支持，以及对假定的NMDA拮抗剂的挑战研究。该中心的总体目标是基于谷氨酸能模型开发新的精神分裂症评估和干预方法

DESCRIPTION (provided by applicant): This is an application for a new Conte Center for Schizophrenia Research based at the New York University School of Medicine (NYUSoM) and the affiliated Nathan Kline Institute for Psychiatric Research (NKI). Schizophrenia (SZ) is associated with sensory processing deficits that represent a core, but understudied, connponent of the disorder. In the auditory system, patients show deficits in basic processes such as tone matching and auditory mismatch negativity (MMN) generation. In the visual system, patients show deficits in processes such as contrast gain and integration that contribute to higher order impairments in processes such as object recognition and face recognition. Sensory deficits may relate specifically to impairments in Nmethyl- D-aspartate (NMDA) receptor-mediated neurotransmission, and are especially amenable to translational investigation using human and animal models. The Center consists of 6 projects and 3 cores, which build from pre-existing collaborations among Center investigators. Projects 1, 2 and 4 are based at NKI/NYSoM and utilize human (Javitt) and primate (Schroeder) neurophysiological, and human postmortem/laser capture microscopy/gene array (Ginsberg/Smiley) approaches to the study of sensory cortical dysfunction and impaired functional connectivity in SZ. Project 3 (Hlllyard) is based at UCSD and investigates modulatory processes underlying normal visual function. Project 5 (Cornblatt) is based at Zucker Hillside Hospital and investigates sensory processing dysfunction within the SZ prodrome. Finally, Project 6 (Weiser) is based at Sheba Hospital/Tel Aviv University and evaluates effectiveness of sarcosine (N-methylglycine), a naturally occurring NMDA agonist not currently available in the US. Cores are devoted to administration (Javitt), patient recruitment/assessment (Butler) and data management/biostatistics (Robinson/Petkova). Although traditional models of SZ focus on dopamine, more recent models focus on underlying glutamatergic dysfunction, and have received support from neurogenetic, imaging, and treatment studies, as well as challenge studies with putative NMDA antagonists. The overall goal of the Center is to develop new assessment and intervention approaches for schizophrenia based upon glutamatergic models