Treating Cognition in Schizophrenia

描述(申请人提供)：精神分裂症患者，尽管接受了最佳剂量的抗精神病药物治疗，以减少或完全消除精神病症状，但仍无法完全恢复功能。研究表明，认知功能障碍和消极症状是导致持续性心理社会功能障碍的原因。该领域最近通过NIMH赞助的Matrics and Turn项目承担了识别、测试和开发精神分裂症认知功能障碍的新疗法的任务(www.MATRICS.ucla.edu)。这些小组的工作已经部分完成，他们已经为我们定义了(1)认知功能障碍的性质，(2)一系列推荐的神经心理学测试来评估这些认知特征，以及(3)可能的认知增强的分子靶点(精神病药理学，2004年6月)。基于大量的基本文献，我们印象深刻的是，它可能不仅是一种药物治疗(例如，本申请中的托莫西汀)，而且还可能是一种心理方法(例如，本申请中的认知补救)，它们需要共同努力，以最佳地改善精神分裂症的认知。因此，我们提出了一个假设，即在认知增强药物的背景下使用认知补救对于精神分裂症的最佳认知改善是必要的。但是，几乎没有直接的初步数据表明哪种药物和哪种认知方法可能有效，也没有什么预期的反应参数(例如，效果大小；应答率；消耗率)。因此，我们正在申请34卢比的拨款，用于试点药物托莫西汀(针对Matrics得分最高的分子靶点之一：前额皮质中的D1多巴胺受体)以及认知补救程序(已经开发，并在初步研究中显示出其自身的前景)，用于治疗精神分裂症的认知功能障碍。我们将在标准的四细胞设计中单独和联合应用每种假定的治疗方法，并评估神经心理功能作为主要结果衡量标准，我们将收集与治疗有关的心理社会改善的初步数据，以确定其时间进程。

DESCRIPTION (provided by applicant): Persons with schizophrenia, despite receiving optimal doses of antipsychotic medications that reduce or entirely obliterate psychotic symptoms still fail to fully recover function. Research has shown that it is the cognitive dysfunction along with the negative symptoms that account for persistent psychosocial dysfunction. The field has recently taken on the task of identifying, testing, and developing new treatments for cognitive dysfunction in schizophrenia through the NIMH-sponsored MATRICS and TURNS projects (www.MATRICS.ucla.edu). The work of these groups is partially completed and they have defined for us (1) the nature of the cognitive dysfunction, (2) a battery of recommended neuropsychological tests to assess these cognitive features, and (3) likely molecular targets for cognitive enhancement (Psychopharmacology, June, 2004). Based on a considerable basic literature, we have been impressed that it may not only be a drug treatment (e.g., atomoxetine in this application) but also psychological approaches (e.g., cognitive remediation, in this application) that are needed to work together to optimally improve cognition in schizophrenia. Therefore, we have developed the hypothesis that the use of cognitive remediation in the context of a cognitive enhancing medication will be necessary for optimal cognitive improvement in schizophrenia. But, little direct preliminary data exist to suggest which drug and which cognitive approach may be effective, nor what the parameters of response to expect (e.g., effect size; response rate; attrition). Therefore, we are applying for a R34 grant to pilot the medication atomoxetine (to target one of MATRICS's highest-scored molecular targets: the D1 dopamine receptor in prefrontal cortex) along with a cognitive remediation routine (one that is already developed and has shown promise by itself in preliminary studies) for the treatment of cognitive dysfunction in schizophrenia. We will apply each putative treatment alone and combined, in a standard four cell design, and evaluate neuropsychological function as the primary outcome measure, and we will collect preliminary data on psychosocial improvements occurring with treatment, to determine its time course.