Enhancing Cognitive Training through Exercise after a First Schizophrenia Episode

描述（由申请人提供）：这项R34申请旨在将我们的创新治疗方法从可行性阶段转移到试点干预试验阶段，以改善精神分裂症的认知。我们提出了一项为期6个月的随机对照试验，将基于神经可塑性的认知训练与释放神经营养素的有氧运动相结合的新型干预措施与单独的相同认知训练相比较。这两种治疗方法都符合NIMH战略计划和NIMH主任Tom Insel的要求，即创造创新的干预措施，可以“广泛传播”，并“以最低的成本随时教授给现有的劳动力”。他说：“治疗的主要目标是整体认知能力及独立生活能力受损。一个次要的结果变量将是一个关键的神经营养生长因子，脑源性神经营养因子（BDNF）。我们假设，将基于神经可塑性的计算机化认知训练和神经营养素增强的体育锻炼相结合，即使相对于单独的认知训练，也会产生较大的认知和功能改善。基于理论考虑和我们最初的试点数据，新的认知训练加有氧运动干预有可能使严重精神疾病患者的生活发生真实的变化。在我们的认知训练计划中加入有氧运动将有助于改善药物副作用， 降低患代谢综合征的风险，并有助于预防精神分裂症发作及其药物治疗后通常出现的身体健康状况恶化。精神分裂症患者的认知缺陷在帮助他们恢复社区功能时面临巨大挑战。认知补救和体育锻炼已分别被证明有希望改善精神分裂症的认知缺陷，但单独使用产生中等效果。我们最初的试点数据表明，整合这两种干预措施比单独的认知训练产生更大的认知收益。我们认为，与定期有氧运动相关的神经营养因子的增加提供了一个平台，允许基于神经可塑性的认知训练对认知的影响程度比通常在单独的认知训练研究中观察到的更大。我们 在精神分裂症首次发作后不久，在确定慢性残疾之前，将认知改善最大限度地推广到功能结局。

DESCRIPTION (provided by applicant): This R34 application is designed to move our innovative treatment approach to improving cognition in schizophrenia from the feasibility stage to the pilot intervention trial stage. We propose a randomized controlled 6-month trial of the efficacy of a novel intervention combining neuroplasticity-based cognitive training with neurotrophin-releasing aerobic exercise, compared to the same cognitive training alone. Both of these treatments address the NIMH Strategic Plan and NIMH Director Tom Insel's request to create innovative interventions that can be "disseminated broadly" and "readily taught to the existing workforce with minimal cost." The primary treatment targets are overall cognitive deficit level and impairment in independent living skills. A secondary outcome variable will be a key neurotrophic growth factor, brain-derived neurotrophic factor (BDNF). We hypothesize that combining neuroplasticity-based computerized cognitive training and neurotrophin-enhancing physical exercise will produce large cognitive and functional improvements, even relative to cognitive training alone. Based on theoretical considerations and our initial pilot data, the new cognitive training plus aerobic exercise intervention has the potential to make a real difference in the lives of individuals with severe mental illness. Adding aerobic exercise to our cognitive training program will have the additional benefit of helping to ameliorate medication side effects, reduce the risk for developing metabolic syndrome, and help to prevent the deterioration in physical health that usually follows the onset of schizophrenia and its pharmacologic treatment. Cognitive deficits in persons with schizophrenia present an enormous challenge when helping them to return to functioning in the community. 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. Our initial pilot data suggest that integrating these two interventions produces larger cognitive gains than the cognitive training alone. We posit that the increases in neurotrophic factors associated with regular aerobic exercise provide a platform which allows neuroplasticity-based cognitive training to impact cognition to a greater degree than is typically observed in studies of cognitive training alone. We target the period shortly after a first episode of schizophrenia to maximize the generalization of cognitive improvement to functional outcome, before chronic disability is established.