Cognitive Remediation of Schizophrenia in a Community Mental Health Setting

描述（由申请人提供）：这项竞争性更新的目的是：1)将我们基于神经可塑性的精神分裂症认知训练的研究从实验室转移到社区环境中；2)在社区支持就业（SE）项目中，证明其作为一种恢复精神分裂症患者认知和增强功能结果的方法的具体效用。在我们基于神经科学的认知训练计划中，用户必须成功地完成数千个逐步增加难度的学习试验，以改善早期感觉、注意力和工作记忆功能的信号-噪声处理。目标是通过在受限和精心控制的条件下利用大脑可塑性机制来促进关键神经认知功能的恢复，而不是促进代偿性认知或行为操作的发展。我们目前基于实验室的随机对照试验（RCT）的数据表明，经过50小时的训练，相对于主动对照，精神分裂症患者在处理速度、工作记忆、语言学习和记忆方面表现出显著的改善（效应值为1.0）。训练后的收益持续6个月，与社会和职业功能和动机的改善显著相关。积极训练的受试者血清BDNF水平也显著升高。为了使这种“恢复性”认知修复方法对精神分裂症患者的健康和康复产生有意义的影响，我们下一阶段的研究必须回答三个关键问题：基于神经可塑性的计算机定向认知训练（TCT）能否在现实世界的临床环境中实施？它是否增强了患者对心理社会康复的反应（以SE的形式），显著改善了功能结局？在SE的情况下，它是否为患者在神经认知和功能方面提供了特定的收益？为了回答这些问题，我们将对慢性精神分裂症患者进行100小时基于神经可塑性的TCT与主动控制条件（100小时图形有趣的电脑游戏）相结合的随机对照试验。这项研究将在旧金山市中心的一个城市社区精神健康中心进行。两组受试者在与研究人员接触的次数和接触电脑的次数方面是相似的，不同之处在于他们是否接受了基于神经可塑性的认知训练方法。受试者将在基线、6个月和12个月时进行神经认知主要结果测量评估。他们将在6个月、12个月、18个月和24个月时接受就业和生活质量的次要结果评估。

DESCRIPTION (provided by applicant): The purpose of this competitive renewal is: 1) To move our study of neuroplasticity-based cognitive training in schizophrenia out of the laboratory and into the community setting; 2) To demonstrate its specific utility as a method for restoring cognition and enhancing functional outcome in schizophrenia patients referred to a community-based supported employment (SE) program. In our neuroscience-based cognitive training program, the user must successfully perform thousands of progressively more difficult learning trials that improve signal-to-noise processing in early sensory, attention, and working memory functions. The goal is to foster the recovery of key neurocognitive functions by harnessing mechanisms of brain plasticity under constrained and carefully controlled conditions, rather than to promote the development of compensatory cognitive or behavioral operations. Data from our current laboratory-based randomized controlled trial (RCT) indicate that, after 50 hours of training and relative to an active control, individuals with schizophrenia show significant improvements in processing speed, working memory, and verbal learning and memory (effect size of 1.0). Gains endure 6 months after training and are significantly associated with improvement in measures of social and occupational functioning and motivation. Active training subjects also show significant increases in serum BDNF levels. In order for this "restorative" cognitive remediation approach to have a meaningful impact on the well- being and recovery of individuals with schizophrenia, our next phase of research must answer three critical questions: Can neuroplasticity-based computerized targeted cognitive training (TCT) be implemented in real- world clinical settings? Does it enhance patients' response to psychosocial rehabilitation (in the form of SE), significantly improving functional outcome? Does it offer patients specific gains in terms of neurocognition and functioning in the context of SE? To answer these questions, we will perform an RCT of 100 hours of neuroplasticity-based TCT vs. an active control condition (100 hours of graphically interesting computer games), when combined with SE for participants with chronic schizophrenia. The study will take place in an urban community mental health center in downtown San Francisco. Both subject groups will be comparable in terms of amount of research staff contact and computer exposure, and will differ only in whether or not they receive an active neuroplasticity- based cognitive training approach. Subjects will be assessed at baseline, and at 6 and 12 months on the primary outcome measures of neurocognition. They will be assessed at 6, 12, 18 and 24 months on secondary outcomes of employment and quality of life. PUBLIC HEALTH RELEVANCE: This purpose of this study is to investigate the usefulness of neuroscience-guided cognitive training combined with community-based supported employment for people with schizophrenia. We will examine the effectiveness of moving our study of neuroplasticity-based restorative targeted cognitive training out of the laboratory and into the community setting; and we will also investigate its utility in enhancing functional outcome in chronically mentally ill adults who are participating in supported employment.