Enhancing Cognitive Training Through Exercise Following a First Schizophrenia Episode

在首次精神分裂症发作后通过锻炼加强认知训练

基本信息

批准号：
9164867
负责人：
KEITH H NUECHTERLEIN
金额：
$ 90.37万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-02 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9164867
关键词：
Address Advocate Aerobic Aerobic Exercise Applications Grants Brain-Derived Neurotrophic Factor Chronic Chronic Schizophrenia Clinical Clinical Trials Cognition Cognitive Cognitive deficits Cognitive remediation Combined Modality Therapy Communities Data Disease Educational Intervention Educational process of instructing Exercise Impaired cognition Individual Intervention Investigational Therapies Lead Measures Meta-Analysis Movement National Institute of Mental Health Neuronal Plasticity Outcome Outcome Measure Outpatients Patients Persons Pharmacological Treatment Physical Exercise Public Health Randomized Controlled Trials Research Priority Schizophrenia Signal Transduction Staging Testing Treatment Efficacy Validation base cognitive function cognitive training computerized cost design disability exercise intervention exercise training first episode schizophrenia functional improvement functional outcomes improved innovation neurotrophic factor novel outcome prediction primary outcome programs psychosocial remediation severe mental illness treatment duration trial comparing

项目摘要

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.

抽象的此 R01 申请涉及我们的创新治疗方法的验证疗效临床试验使用 NIMH 倡导的实验性治疗设计来改善精神分裂症的认知能力。干预方法将释放神经营养素的有氧运动训练与基于神经可塑性的训练相结合认知训练以增强认知训练对认知和功能结果的影响。认知训练和锻炼解决了 NIMH 战略研究重点，以创造创新可以“广泛传播”和“以最少的成本随时向现有劳动力传授干预措施” 认知矫正和体育锻炼都被证明有希望降低成本。” 改善精神分裂症的认知缺陷，但单独使用对慢性病产生中等效果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和精神分裂症患者。我们发现 BDNF 的增加与临床结果相关。定期有氧运动提供了一个平台，可以让基于神经可塑性的认知训练增强认知程度比单独认知训练研究中通常观察到的要高。将体育锻炼与认知训练相结合将产生更大的功能性相对于单独的认知训练而言，这项验证性疗效临床试验是有证据指导的。来自我们当前的 R34 试点随机对照试验，比较联合治疗与认知训练我们发现了 BDNF 目标参与和差异改善的令人信服的证据。认知和功能结果，以及从最初的 BDNF 增益预测后期结果支持针对认知缺陷患者开展全面的验证性疗效临床试验。精神分裂症对成功恢复社会功能提出了巨大的挑战。精神分裂症首次发作后不久的时期，以最大限度地概括认知在慢性残疾建立之前改善现实世界的功能结果。另外，有氧运动干预有可能检查已发展的作用机制并对严重精神疾病患者的生活产生有意义的影响。