Neuropsychological Impairment In Schizophrenia

精神分裂症的神经心理损伤

• 批准号: 6541819
• 负责人: Terry E Goldberg
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6541819
• 关键词: behavioral genetics; brain injury; clinical research; cognition; cognition disorders; disease /disorder proneness /risk; genetic markers; human subject; memory; mental disorder diagnosis; neural information processing; neuropsychological tests; neuropsychology; schizophrenia; semantics

Over the past year we have attempted to characterize more completely the cognitive disturbances in schizophrenia. In particular we have begun work on the mechanisms accounting for failures in memory in schizophrenia. Patients' difficulties do not appear to be due to qualitative abnormalities in susceptibility to interference, encoding, or so called false memory problems. We have begun to comnputationally model the episodic memory impairments in schizophrenia in order to determine if they are due to general noise or a single stage in mnemonic processing. We have examined disorganized speech in schizophrenia using various semantic processing paradigms. In general patients have difficulties not with the size of their lexicon but rather how they access it automatically, as evidenced in priming paradigms. Thus, we have devised a battery of novel experimental tasks to assess whether schizophrenic patients show a dissociation between lexical integrity and semantic abnormality. This study utilizes patients with schizophrenia, patients with Alzheimer's disease and children to find dissociations between the size of the verbal lexicon and its organization. If this is the case then it has important implications for normal cognitive architecture. We have also found using both a nonverbal morphing task and a reaction time task that patients do not have undue difficulty with understanding what an entitiy is, it is their ability to understand the relations between things that is abnormal. We have begun work on a study which compares the integrity of the internal representation itself to the integrity of activation among representations using various types of number priming Finally, a genetic study of schizophrenia with an emphasis on intermediate phenotypes is ongoing. We are using a large battery of neurocognitive measures to characterize this "intermediate" phenotype. We base this on the rationale that patients do not inherit schizophrenia per se but a variety of susceptibilities to cognitive impairments and their attendant neurophysiologic abnormalities. We have already found that some cognitive measures yield high relative risks that are not redundant with diagnosis. These include episodic memory tasks and an N-Back working memory task with high demands for temporal encoding and information updating.Moreover, we have identified a gene (COMT) that has an impact on the N Back through dopamine signaling.

在过去的一年里，我们试图更全面地描述精神分裂症患者的认知障碍。特别是，我们已经开始研究精神分裂症患者记忆障碍的机制。患者的困难似乎并不是由于对干扰、编码或所谓的虚假记忆问题的易感性的质量异常。我们已经开始对精神分裂症患者的情景记忆障碍进行计算机模拟，以确定它们是由一般噪声还是记忆加工的单个阶段造成的。我们使用不同的语义处理范式研究了精神分裂症患者的无组织言语。一般来说，患者遇到的困难不是词汇量的大小，而是他们如何自动获取词汇量，这在启动范式中得到了证明。因此，我们设计了一系列新的实验任务来评估精神分裂症患者是否表现出词汇完整性和语义异常之间的分离。这项研究利用精神分裂症患者、阿尔茨海默病患者和儿童来发现词汇的大小和组织之间的分离。如果是这样的话，它对正常的认知架构有重要的影响。我们还发现，同时使用非语言变形任务和反应时任务，患者在理解实体是什么方面并没有不必要的困难，这是他们理解不正常事物之间关系的能力。我们已经开始了一项研究，使用各种类型的数字启动来比较内部表征本身的完整性和表征之间激活的完整性。最后，一项强调中间表型的精神分裂症的遗传学研究正在进行中。我们正在使用大量的神经认知测量方法来描述这种“中间”表型。我们基于这样的理论基础，即患者本身并不遗传精神分裂症，而是各种认知障碍及其伴随的神经生理异常的易感性。我们已经发现，一些认知测量方法会产生与诊断无关的高相对风险。这些任务包括情节记忆任务和对时间编码和信息更新有很高要求的N-back工作记忆任务。此外，我们还发现了一个通过多巴胺信号对N-back产生影响的基因(COMT)。