Treating Cognition in Schizophrenia

描述（由申请人提供）：精神分裂症患者，尽管接受了最佳剂量的抗精神病药物，减少或完全消除精神病症状，但仍未能完全恢复功能。研究表明，正是认知功能障碍加上负面症状导致了持续的社会心理功能障碍。该领域最近通过nimh赞助的matrix和TURNS项目（www.MATRICS.ucla.edu）承担了识别、测试和开发精神分裂症认知功能障碍新疗法的任务。这些小组的工作已经部分完成，他们为我们定义了(1)认知功能障碍的本质，(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)认知增强的可能分子靶点（精神药理学，2004年6月）。基于相当多的基础文献，我们印象深刻的是，它可能不仅是一种药物治疗（例如，在这个应用中，托莫西汀），而且还需要心理方法（例如，认知补救，在这个应用中）共同努力，以最佳地改善精神分裂症患者的认知。因此，我们提出了一种假设，即在认知增强药物的背景下使用认知修复对于精神分裂症患者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，也没有预期的反应参数（例如，效应大小；反应率；损耗）。因此，我们正在申请R34拨款，以试点药物阿托西汀（针对一个矩阵得分最高的分子靶点：前额皮质D1多巴胺受体）和认知修复常规（一个已经开发出来的，并在初步研究中显示出希望）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或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测量，我们将收集治疗后发生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.