Enhancing Cognitive Training Through Exercise Following a First Schizophrenia Episode

摘要 此R01应用程序涉及我们的创新治疗方法的确证疗效临床试验 使用NIMH倡导的实验性治疗设计，改善精神分裂症的认知。我们的 神经营养素释放有氧运动训练与神经可塑性相结合的干预方法 认知训练增强认知训练对认知和功能结果的影响。两者都有 认知培训和练习解决了NIMH创造创新的战略研究重点 干预措施可以“广泛传播”并“以最低限度的成本随时传授给现有的劳动力” 成本。“认知补救和体育锻炼分别被证明有希望 改善精神分裂症患者的认知缺陷，但单独使用对慢性精神分裂症患者效果适中 精神分裂症患者。我们将使用脑源性神经营养因子(BDNF)作为我们的目标和认知，并 功能结果与我们的临床结果一样。我们假设脑源性神经营养因子的增加与 有规律的有氧运动提供了一个平台，使基于神经可塑性的认知训练能够增强 认知能力比仅在认知训练研究中观察到的程度更高。我们假设 将体育锻炼与认知训练相结合将产生更大的认知和功能 相对于单独的认知训练，这是一种改进。这项证实疗效的临床试验是以证据为指导的。 从我们目前的R34试点随机对照试验中比较综合治疗和认知训练 没有体育锻炼。我们发现了令人信服的证据，表明BDNF的目标参与、差异化改进 在认知和功能结果方面，以及从初始BDNF增加到如此强烈的未来结果的预测 支持向全功率确证疗效临床试验的方向发展。精神分裂症患者的认知缺陷 精神分裂症对成功恢复社区功能是一个巨大的挑战。我们的目标是 精神分裂症第一次发作后不久的时间段，以最大限度地概括认知 在确定慢性残疾之前，改善真实世界的功能结果。认知训练 再加上有氧运动干预，有可能检验假想的作用机制，并 对患有严重精神疾病的人的生活产生有意义的影响。

ABSTRACT This R01 application involves a confirmatory efficacy clinical trial of our innovative treatment approach to improving cognition in schizophrenia, using an experimental therapeutic design that NIMH has advocated. Our intervention approach combines neurotrophin-releasing aerobic exercise training with neuroplasticity-based cognitive training to enhance the impact of cognitive training on cognition and functional outcome. Both cognitive training and exercise address the NIMH strategic research priorities for creating innovative interventions that can be “disseminated broadly” and “readily taught to the existing workforce with minimal cost.” Cognitive remediation and physical exercise have each been shown separately to have promise for improving cognitive deficits in schizophrenia, but used separately yield moderate effects in chronic schizophrenia patients. We will use brain-derived neurotrophic factor (BDNF) as our target and cognition and functional outcome as our clinical outcomes. We hypothesize that the increases in BDNF associated with regular aerobic exercise provide a platform which allows neuroplasticity-based cognitive training to enhance cognition to a greater degree than is typically observed in studies of cognitive training alone. We hypothesize that combining physical exercise with cognitive training will produce larger cognitive and functional improvements, relative to cognitive training alone. This confirmatory efficacy clinical trial is guided by evidence from our current R34 pilot randomized controlled trial comparing the combined treatment with cognitive training without physical exercise. We find compelling evidence of BDNF target engagement, differential improvement in cognition and functional outcome, and prediction of later outcome from initial BDNF gain that strongly supports the movement to a fully powered confirmatory efficacy clinical trial. Cognitive deficits in persons with schizophrenia present an enormous challenge to successful return to functioning in the community. We target the period shortly after a first episode of schizophrenia to maximize the generalization of cognitive improvement to real-world functional outcome, before chronic disability is established. The cognitive training plus aerobic exercise intervention has the potential to examine a hypothesized mechanism of action and to make a meaningful difference in the lives of individuals with severe mental illness.