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

描述（由申请人提供）：来自动物文献、健康人群和精神分裂症研究的累积证据表明，定期锻炼对神经发生、突触可塑性和认知等整体功能有积极影响。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改善和症状水平的降低有关。由于运动已被发现刺激人类内侧颞叶神经发生，相关的异常已被广泛观察到精神分裂症的研究，体力活动可能是一个重要的干预。在精神病前驱症状期间，即精神病性障碍正式发作之前的一段时间，青少年经历轻微的减弱症状，伴随认知退化和社会职业功能的全面下降，并且在两年期间内有10-35%的青少年继续转变为精神病性障碍，如精神分裂症。尽管运动干预的承诺，以及内侧颞叶异常在精神病的病因模型中发挥的关键作用，但还没有对超高危青年（UHR）进行有氧运动的实验研究。了解有氧运动对UHR青少年的潜在益处是不可或缺的，因为前驱症状是一个可行的干预时期，在此期间仍有相当多的大脑发育。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越来越大，因此了解运动对各自大脑行为的影响具有相当大的希望。迫切需要实验研究来确定规定的有氧运动是否可以刺激颞中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，一个由经验丰富的前驱期和运动研究人员组成的专家团队将通过12周的运动试验跟踪一组15名UHR青少年和年轻人（年龄16-24岁），以确定参与者可耐受的运动强度/频率水平，以及改善有氧健身的最佳水平（65%）。 最大摄氧量和每周2次训练与85%强度和每次3次训练），如果有氧体能改善（即，VO 2 max、VO 2 peak、解释阈值）与内侧颞叶结构体积（海马和海马旁回）的增加和伴随的认知功能改善（即，包括已知在内侧颞叶结构上大量招募的任务）以及行为学和社会/角色功能。如果达到基准，这些数据将用于简化一项为期三年的评估者盲法对照试验（15例UHR-运动，15例UHR-等待-对照），以确定干预措施在以下方面的疗效： 促进中颞健康以及伴随的认知、临床和社会职业功能改善。参与者将接受长达24个月的随访，以确定干预是否对临床病程和向精神病转变产生影响。总的来说，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，并有可能为UHR青少年提供有前途的新治疗方法。

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.