The Conte Center for Schizophrenia Research

描述（由申请人提供）：这是一个新的康特精神分裂症研究中心的申请，该中心位于纽约大学医学院（NYUSoM）和附属的内森克莱恩精神病学研究所（NKI）。精神分裂症（SZ）与感觉处理缺陷有关，这是精神分裂症的一个核心，但尚未得到充分研究。在听觉系统中，患者在基本过程中表现出缺陷，例如音调匹配和听觉失配负波（MMN）生成。在视觉系统中，患者在诸如对比度增益和整合等过程中表现出缺陷，这些缺陷导致诸如物体识别和面部识别等过程中的高阶损伤。感觉缺陷可能与N-甲基-N- D-天冬氨酸（NMDA）受体介导的神经传递，特别是服从 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，这些项目和核心是由中心研究人员之间预先存在的合作建立的。项目1、2和4基于NKI/NYSoM，利用人类（Javitt）和灵长类动物（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的感觉皮层功能障碍和功能连接受损。项目3（Hlllyard）是基于加州大学圣地亚哥分校，并研究调节过程的基础上正常的视觉功能。项目5（Cornblatt）位于Zucker希尔赛德医院，研究SZ前驱症状内的感觉处理功能障碍。最后，项目6（Weiser）位于Sheba医院/特拉维夫大学，评估肌氨酸（N-甲基甘氨酸）的有效性，肌氨酸是一种天然存在的NMDA激动剂，目前在美国不可用。核心致力于管理（Javitt）、患者招募/评估（Butler）和数据管理/生物统计学（罗宾逊/Petkova）。虽然传统的SZ模型集中在多巴胺，最近的模型集中在潜在的多巴胺能功能障碍，并得到了支持，神经遗传学，成像和治疗研究，以及挑战研究与假定的NMDA拮抗剂。该中心的总体目标是根据精神分裂症模型开发新的评估和干预方法

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