Aerobic Exercise for Cognition in Schizophrenia

 描述（由申请人提供）： 精神分裂症（SCZ）是一种严重的，慢性的，致残的精神病，影响大约87，000退伍军人。关键的日常功能的表现缺陷是SCZ的重要和悲惨的后果。减少残疾的康复治疗有可能使几乎每一位SCZ患者受益。 SCZ的认知有可能通过行为干预来增强。大脑的变化已被证明是伴随着认知训练后，在SCZ，如大脑可塑性的标志物（脑源性神经营养因子，BDNF）的增加，和正常化的措施，是依赖于海马增强认知。由于已知SCZ中的海马异常及其与认知受损的联系，海马的这一发现很重要。患有SCZ的参与者能够参加有氧运动（AE）训练并获得健身。一项小型研究报告称，与对照非有氧运动相比，AE改善了短期记忆，但样本量限制为每组8例。重要的是，这项研究发现海马体积的增加与有氧健身和认知能力的改善有关。 已知AE赋予许多身体健康益处。动物和健康老龄人群中的AE文献为本SCZ项目提供了信息。最近的一些研究表明，AE与健康老龄化受试者的认知增益相关，这些增益与海马体积增加相关，而海马体积增加又与BDNF和心血管健康增加相关。大鼠脑源性神经营养因子mRNA表达增加，这主要发生在海马。总之，这些临床前和临床研究与以下假设一致：AE通过健身增加诱导BDNF增加，导致大脑变化，特别是（但不一定限于）有助于AE认知增益的海马体。SCZ中海马体积的减少与正常衰老中海马体积的损失之间存在平行关系。这是可能的，一个类似的机制可能是潜在的认知增益与AE在SCZ。 AE是一种潜在的重要手段，以改善认知在SCZ，但工作的认知效应的AE在SCZ是令人惊讶的稀疏。该项目将填补这一重要的知识空白。本研究将是一项随机化、评估者盲态平行研究 在40名年龄在18-70岁的SCZ或情感障碍患者中进行为期12周的AE训练与由伸展运动组成的对照条件（CONT）的组临床试验。该项目的具体目标是：具体目标1：在训练结束时（12周），在SCZ VA参与者中比较AE训练与CONT条件的可行性和有效性。我们预测，在我们的VA人群中完成这项训练是可行的，并且AE组将表现出比CONT组显著更大的认知改善（通过改善精神分裂症共识认知成套测验（MCCB）中认知的测量和治疗研究进行测量）。培训后8周随访时的MCCB将作为次要结局。具体目标2：评估心血管健康的增加是否介导认知改善。在AE与CONT干预12周前后以及训练后8周随访时，将采用可靠有效的摄氧量（VO 2 max）指标评估心血管健康。最大摄氧量估计值是最合适的测试，因为它考虑了参与者的初始健康水平，而没有完全最大摄氧量测试的体力消耗和恐惧体验。我们预测，AE组的估计VO 2 max改善将预测训练12周和训练后8周随访的认知增益。具体目标3：比较日常功能性能力（U。加州圣地亚哥基于绩效的技能评估，UPSA）在AE与CONT组。我们预测，在训练后12周和8周随访时，AE组的UPSA将比CONT组有更大的改善。

 DESCRIPTION (provided by applicant): Schizophrenia (SCZ) is a severe, chronic, and disabling psychotic illness that affects approximately 87,000 Veterans. Deficits in the performance of critical everyday functions are important and tragic consequences of SCZ. Rehabilitative treatment for disability reduction has the potential to benefit nearly every patient with SCZ. Cognition in SCZ has the potential to be enhanced by behavioral interventions. Brain changes have been shown to accompany enhanced cognition after cognitive training in SCZ, such as increases in a marker of brain plasticity (brain-derived neurotrophic factor, BDNF), and normalization of a measure that is dependent on the hippocampus. This hippocampal finding is important because of known hippocampal abnormalities in SCZ and their link to impaired cognition. Participants with SCZ are capable of participating in aerobic exercise (AE) training and making gains in fitness. One small study reported improved short-term memory with AE compared to a control non-aerobic exercise, but the sample size was limited to 8 per group. Importantly, this study found increased hippocampal volume that correlated with gains in aerobic fitness and with cognitive improvement. AE is known to confer many physical health benefits. The AE literature in animals and healthy aging populations is informative for this SCZ project. A number of recent studies indicate that AE is associated with cognitive gains in healthy aging subjects, and these gains correlate with hippocampal volume increases, that in turn correlate with increased BDNF and cardiovascular fitness. AE in rats increases BDNF mRNA, and this occurs prominently in the hippocampus. Taken together, these preclinical and clinical studies are consistent with the hypothesis that AE, via increases in fitness, induce BDNF increases that lead to brain changes, particularly (but not necessarily limited to) the hippocampus that subserve cognitive gains with AE. There are parallels between the reduced hippocampal volume in SCZ and the hippocampal volume loss seen with normal aging. It is possible that a similar mechanism may underlie potential cognitive gains with AE in SCZ. AE is a potentially important means to improve cognition in SCZ, but work on the cognitive effects of AE in SCZ is surprisingly sparse. This project will fill this important knowledge gap. The study will be a randomized rater blind parallel group clinical trial to compare twelve weeks of AE training with a control condition (CONT) consisting of stretching exercises in 40 participants aged 18-70 with SCZ or schizoaffective disorder. Specific Aims of the project are: Specific Aim 1: Compare the feasibility and effectiveness of AE training to a CONT condition at the end of training (12 weeks) in VA participants with SCZ. We predict that completion of this training will be feasible in our VA population, and that the AE group will exhibit significantly greater cognitive improvement than the CONT group (measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery, MCCB). MCCB at 8 weeks post-training follow up will be a secondary outcome. Specific Aim 2: Evaluate whether increases in cardiovascular fitness mediate cognitive improvement. Cardiovascular fitness will be estimated with a reliable and valid measure of oxygen uptake (VO2max) prior to and after 12 weeks of the AE vs. CONT intervention and at 8 weeks post-training follow up. Estimated VO2max is the most appropriate test as it accounts for initial fitness level of the participant without the physically exhausting and frightening experience of a full V02max test. We predict that estimated VO2max improvement in the AE group will predict cognitive gain with training at 12 weeks and 8 weeks post-training follow up. Specific Aim 3: Compare changes in measures of everyday functional abilities (U. California San Diego Performance-Based Skills Assessment, UPSA) in the AE vs. CONT groups. We predict that the AE group will show greater gains in the UPSA than the CONT group at 12 weeks and 8 weeks post-training follow up.