Exercise and markers of medial temporal health in youth at-risk for psychosis

有精神病风险的青少年的运动和内侧颞叶健康指标

• 批准号: 9131473
• 负责人: Angela Bryan
• 金额: $ 23.85万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-28 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9131473
• 关键词: Adherence; Adolescent; Adolescent and Young Adult; Adverse effects; Aerobic Exercise; Affect; Age; Animals; Area; Attenuated; Benchmarking; Brain; Cardiovascular system; Chronically Ill; Clinical; Cognition; Cognitive; Control Groups; Coupled; Data; Deterioration; Development; Effectiveness; Episodic memory; Exercise; Exercise Physiology; Feeling; Frequencies; Future; Goals; Health; Hearing; Hippocampus (Brain); Human; Individual; Intervention; Lead; Learning; Light; Literature; Measures; Medial; Memory; Mental disorders; Modeling; Neurobehavioral Manifestations; Neuronal Plasticity; Occupational; Outcome; Parahippocampal Gyrus; Participant; Patients; Phase; Physical activity; Pilot Projects; Play; Population; Psychotic Disorders; Quality of life; Randomized; Recruitment Activity; Research Personnel; Risk; Role; Schizophrenia; Shapes; Short-Term Memory; Specificity; Staging; Structure; Symptoms; Synaptic plasticity; Temporal Lobe; Testing; Treatment Efficacy; VO2max; Verbal Learning; Waiting Lists; Youth; actigraphy; base; blind; brain behavior; brain health; cell growth; cognitive function; control trial; cost; data integrity; design; exercise intensity; exercise intervention; exercise prescription; experience; fitness; follow-up; functional decline; functional improvement; high risk; human subject protection; improved; meetings; neurogenesis; neuroimaging; prevent; research study; response; social; sound; symptomatology; vigorous intensity

DESCRIPTION (provided by applicant): Accumulating evidence from the animal literature, healthy populations, and schizophrenia studies suggests that regular exercise positively affects integral functions such as neurogenesis, synaptic plasticity and cognition. Likewise, preliminary evidence suggests that aerobic activity has been associated with improved quality of life and a lower level of symptoms in patients with schizophrenia. Because exercise has been found to stimulate human medial temporal neurogenesis, and related abnormalities have been widely observed in studies of schizophrenia, physical activity may be in an important intervention. During the psychosis prodrome, a period immediately preceding formal onset of psychotic disorders, adolescents experience subtle attenuated symptoms coupled with cognitive deterioration and a global decline in socio-occupational functioning and anywhere between 10-35% go on to transition to a psychotic disorder such as schizophrenia in a two-year period. Despite the promise of exercise interventions, and the critical role medial temporal lobe abnormalities play in etiological models of psychosis, there have been no experimental studies of aerobic exercise in ultra-high risk youth (UHR). Understanding the potential benefits of aerobic exercise in UHR youth is integral as the prodrome is a viable period of intervention in which considerable brain development is still occurring. Further, as there have been challenges associated with many of the available interventions, and an increasing level of potential found in neuroplasticity-based interventions, understanding the effect of exercise on respective brain-behavior holds considerable promise. Experimental research is sorely needed to determine if prescribed aerobic exercise can stimulate medial-temporal neurogenesis and ameliorate cognition and symptoms/functioning in this vital group. In the proposed study, an expert team of experienced prodromal and exercise investigators will follow a group of 15 UHR adolescent and young adults (ages 16-24) through a 12 week exercise trial to determine which level of exercise intensity/frequency is tolerable for participants and optimal for improving aerobic fitness (65% of VO2max and 2 sessions per week versus 85% intensity and 3 sessions per peek) and if improvements in aerobic fitness (i.e., VO2max, VO2peak, ventilatory threshold) are associated with increases in medial temporal structure volume (hippocampus and parahippocampal gyrus) and accompanying improvements in cognitive function (i.e., including tasks known to recruit heavily on medial temporal structures) as well as symptomatology and social/role functioning. If the benchmarks are met, this data will be used to streamline a three-year rater-blind controlled trial (15 UHR-exercise, 15 UHR waitlisted-control) to determine the efficacy of the intervention in promoting medial temporal health as well as accompanying cognitive, clinical, and socio-occupational function improvement. Participants will be followed up to 24-months to determine if the intervention has an affect on clinical course and transition to psychosis. Taken together, this study is important for understanding the lessons necessary for planning a future large-scale trial, and has the potential to shed light on a promising new treatment for UHR youth.

描述（由申请人提供）：从动物文献、健康人群和精神分裂症研究中积累的证据表明，定期锻炼会对神经发生、突触可塑性和认知等整体功能产生积极影响。同样，初步证据表明，有氧活动与精神分裂症患者生活质量的提高和症状的降低有关。由于运动被发现可以刺激人类内侧颞神经发生，并且在精神分裂症的研究中广泛观察到相关异常，因此体力活动可能是一种重要的干预措施。在精神病前驱症状期间，即精神障碍正式发作之前的一段时期，青少年会经历微妙的减弱症状，伴有认知恶化和社会职业功能的整体下降，并且 10-35% 的青少年会继续转变为精神障碍，例如两年内患精神分裂症。尽管运动干预有希望，并且内侧颞叶异常在精神病的病因模型中发挥着关键作用，但目前还没有针对超高危青少年（UHR）进行有氧运动的实验研究。了解有氧运动对 UHR 青少年的潜在益处至关重要，因为前驱症状是一个可行的干预时期，在此期间大脑仍在发育。此外，由于许多可用的干预措施都存在挑战，并且基于神经可塑性的干预措施的潜力不断增加，因此了解运动对相应大脑行为的影响具有很大的希望。迫切需要实验研究来确定规定的有氧运动是否可以刺激内侧颞叶神经发生并改善这一重要群体的认知和症状/功能。在拟议的研究中，由经验丰富的前驱和运动调查员组成的专家团队将跟踪一组由 15 名 UHR 青少年和年轻人（16-24 岁）进行的为期 12 周的运动试验，以确定参与者可以忍受的运动强度/频率水平是改善有氧健身的最佳选择（65% 最大摄氧量和每周 2 次训练对比 85% 强度和每次 3 次训练）以及有氧适能（即最大摄氧量、峰值摄氧量、通气阈）的改善是否与内侧颞叶结构体积（海马和海马旁回）的增加以及伴随的改善相关认知功能（即，包括已知大量消耗内侧颞结构的任务）以及症状学和社会/角色功能。如果达到基准，该数据将用于简化为期三年的评估者盲对照试验（15 项 UHR 练习，15 项 UHR 候补对照），以确定干预措施的有效性 促进内侧颞叶健康以及伴随的认知、临床和社会职业功能的改善。参与者将接受长达 24 个月的随访，以确定干预措施是否对临床病程和向精神病的转变产生影响。综合起来，这 这项研究对于了解规划未来大规模试验所需的经验教训非常重要，并且有可能为 UHR 青少年提供一种有前景的新治疗方法。