CORTICAL MECHANISMS IN SCHIZOPHRENIA

拟建中心的长期目标是提供一个 神经生物学框架的理解，并最终 治疗或预防精神分裂症的基本特征。这个 潜在的假设是无序的思维过程和 精神分裂症患者的情感反应反映了信息的缺乏 特异性皮质醇的加工与调控机制 皮质和皮质下环路涉及早发性，但不 只有前额叶皮质。两国之间的关系 前额叶皮质和精神分裂症对科学家和 来自本世纪初的临床医生，证据表明 随着神经科学的进步和 医药。一组来自不同部门的调查人员 以及跨六个机构(耶鲁、哈佛、麦克莱恩)的学科 医院、弗吉尼亚州西黑文、Salpetriere、巴斯德研究所) 在这一努力中联合起来。六个项目包括1)单元格 正常恒河猴在执行任务时的录音 假设心理过程与 精神分裂症；2)眼动跟踪和认知缺陷的研究 精神分裂症患者和具有前额叶的非人灵长类动物 皮质损害以确定疾病的常见元素和 其皮质定位；3)细胞学和 光照和光照下的免疫组织化学分析 针对精神分裂症皮质的电子显微镜水平 识别特定途径中的结构或生化损伤； 4)对比受体放射自显影分析 大脑皮质部分区域的CCK和5-羟色胺受体 精神分裂症和非人灵长类大脑；5)行为，透析 以及灵长类动物模型的受体放射自显影研究 解决精神分裂症的选择性症状，例如苯丙胺- 诱发的“精神病”或诱发条件，例如， 成人多巴胺的药理耗竭与应激效应 恒河猴及其对前额叶皮质的依赖，以及6) 选择性地塞米松诱导发育动物模型的建立 删除符合以下条件的可指定的皮质-皮质元素 被认为对信息处理是必不可少的 被认为对精神分裂症很重要的回路。本中心 代表了一项多学科、可比较的倡议，以揭示 精神分裂症合并进展期的生物学基础 神经生物学、神经心理学和分子技术， 交织在一起，有坚实的理论基础和支撑 可检验的假设。

The long-range goal of the proposed Center is to provide a neurobiological framework for understanding and ultimately treating or preventing the cardinal features of schizophrenia. The underlying hypothesis is that the disordered thought processes and affective responses in schizophrenia reflect deficient information processing and regulatory mechanisms of specificable cortico- cortical and subcortical circuits involving premarily but not exclusively the prefrontal cortex. A relationship between the prefrontal cortex and schizophrenia was evident to scientists and clincians from the early part of this century and the evidence has grown more compelling with advances in neuroscience and medicine. A team of investigators from different departments and disciplines spanning six institutions (Yale, Harvard, McLean Hospital, West Haven VA, Salpetriere, Pasteur Institute) have joined together in this effort. Six projects include 1) single cell recordings in normal rhesus monkeys performing tasks that tap psychological processes hypothesized to be relevant to schizophrenia; 2) the study of eye tracking and cognitive deficits in schizophrenic patients and nonhuman primates with prefrontal cortical lesions to identify common elements of the disorder and their cortical localization; 3) cytological and immunohistochemical analysis at the light and electronmicroscopic level of schizophrenic cortex aimed at identifying structural or biochemical lesions in specific pathways; 4) comparative receptor autoradiographic analysis of D1, D2, CCK and 5-HT receptors in selected cortical areas of the schizophrenic and nonhuman primate brain; 5) behavioral, dialysis and receptor-autoradiographic studies of primate models which address selective symptoms of schizophrenic, e.g., amphetamine- induced "psychosis" or precipitating conditions, e.g., pharmacological depletion of dopamine and stress effects in adult rhesus monkey and their dependence on prefrontal cortex, and 6) developmental induction of an animal model with selective deletion of specifiable cortico-cortical elements that are hypothesized to be essential for the information-processing circuits deemed to be important in schizophrenia. This Center represents a multidisciplinary, comparative initiative to uncover the biological foundations of schizophrenia combining advanced neurobiological, neuropsychological, and molecular techniques, intertwined and supported by a strong theoretical base and testable hypotheses.