Aerobic Exercise for Cognition in Schizophrenia

有氧运动对精神分裂症认知能力的影响

• 批准号: 9212013
• 负责人: Erica J Duncan
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9212013
• 关键词: Activities of Daily Living; Aerobic Exercise; Affect; American; Animals; Behavior Therapy; Brain; Brain-Derived Neurotrophic Factor; California; Cardiovascular system; Chronic; Clinical Research; Clinical Trials Cooperative Group; Cognition; Cognitive; Consensus; Delusions; Effectiveness; Employment; Exercise; Exhibits; Hallucinations; Health Benefit; Hippocampus (Brain); Impaired cognition; Impairment; Independent Living; Intervention; Knowledge; Lead; Life; Link; Literature; Maintenance; Measurement; Measures; Mediating; Medication Management; Messenger RNA; Mission; Modality; Motivation; Occupational; Oxygen; Participant; Patients; Performance; Pharmaceutical Preparations; Plasma; Population; Psychotic Disorders; Randomized; Rattus; Rehabilitation therapy; Reporting; Research; Resistance; Sample Size; Schizoaffective Disorders; Schizophrenia; Self Care; Short-Term Memory; Social Functioning; Stretching; Symptoms; Testing; Training; Veterans; Work; aged; base; blind; cognitive enhancement; cognitive function; cognitive skill; cognitive training; disability; exercise training; exhaust; experience; fitness; follow-up; healthy aging; improved; normal aging; physical conditioning; preclinical study; public health relevance; secondary outcome; sensory gating; skills; social; uptake

 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.

 描述(由申请人提供)： 精神分裂症(SCZ)是一种严重、慢性和致残的精神疾病，约有87,000名退伍军人受到影响。关键日常功能的执行缺陷是SCZ的重要和悲剧性后果。减少残疾的康复治疗有可能使几乎每一位SCZ患者受益。SCZ的认知能力有可能通过行为干预得到提高。在SCZ进行认知训练后，大脑的变化被证明伴随着认知的增强，例如大脑可塑性的标志(脑源性神经营养因子，BDNF)的增加，以及依赖于海马体的测量的正常化。这一海马区的发现很重要，因为已知的海马区异常及其与认知损害的联系。患有SCZ的参与者能够参加有氧运动(AE)训练，并在健康方面取得进展。一项小型研究报告称，与对照组的非有氧运动相比，AE改善了短期记忆，但样本量限制为每组8人。重要的是，这项研究发现，海马体体积的增加与有氧健身能力的提高和认知能力的改善有关。众所周知，AE对身体健康有很多好处。动物和健康老龄化人群中的声发射文献为这个SCZ项目提供了信息。最近的一些研究表明，在健康老龄化的受试者中，AE与认知能力的提高有关，这些能力的提高与海马体体积的增加相关，而海马体体积的增加又与脑源性神经营养因子的增加和心血管健康相关。大鼠脑梗塞后BDNF基因表达增加，主要发生在海马区。综上所述，这些临床前和临床研究与这样的假设是一致的，即AE通过增加适应性，诱导BDNF增加，从而导致大脑变化，特别是(但不一定限于)海马体，它削弱了AE的认知获得。SCZ患者的海马体体积缩小与正常衰老时所见的海马体体积减少有相似之处。有可能类似的机制可能是SCZ中潜在的认知能力增强的基础。声发射是一种潜在的改善SCZ认知的重要手段，但关于声发射在SCZ中的认知效应的研究却少之又少。这个项目将填补这一重要的知识空白。这项研究将是随机的评分者盲目平行 分组临床试验，对40名18-70岁患有SCZ或分裂情感障碍的参与者进行12周的AE训练与由伸展运动组成的对照条件(CONT)的比较。该项目的具体目标是：具体目标1：比较患有精神分裂症的退伍军人在训练结束时(12周)接受AE训练的可行性和有效性。我们预测，在我们的VA人群中完成这项培训将是可行的，并且AE组将比CONT组表现出显著的认知改善(通过测量和治疗研究改善精神分裂症共识认知电池中的认知)。MCCB在培训后8周的随访将是次要的结果。具体目标2：评估心血管健康水平的提高是否会促进认知能力的改善。心血管健康状况将通过可靠和有效的摄氧量(VO2max)测量来评估，在AE和CONT干预12周之前和之后，以及训练后8周的随访中。估计最大摄氧量是最合适的测试，因为它考虑了参与者的初始健康水平，而不会有完整的最大摄氧量测试的体力消耗和可怕体验。我们预测，在训练后12周和8周的随访中，AE组估计的最大摄氧量改善将预测认知能力的提高。具体目标3：比较AE组和CONT组日常功能能力(加州大学圣地亚哥分校绩效技能评估，UPSA)的变化。我们预测，在训练后12周和8周的随访中，AE组将比CONT组在UPSA上表现出更大的进步。