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越来越多的证据表明，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，有氧运动与改善精神分裂症患者的生活质量和降低症状水平有关。由于已经发现运动可以刺激人类内侧颞神经的发生，并且在精神分裂症的研究中广泛观察到相关的异常，因此体育活动可能是一个重要的干预措施。在精神病前驱期，即紧接在精神病正式发病之前的一段时间，青少年会经历轻微的症状减弱，并伴有认知退化和社会职业功能的全面下降，在任何地方，10-35%的青少年会在两年内过渡到精神分裂症等精神病。尽管运动干预有望实现，而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风险青年（UHR）进行有氧运动的实验研究。了解有氧运动对UHR青年的潜在益处是不可或缺的，因为前驱期是一个可行的干预时期，在此期间仍在发生相当大的大脑发育。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前景。目前迫切需要实验研究来确定有氧运动是否能刺激颞叶内侧神经发生，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症状和运动调查员组成的专家团队将对一组15名UHR青少年和年轻人（16-24岁）进行为期12周的运动试验，以确定哪种运动强度/频率对参与者来说是可容忍的，并且对改善有氧健康是最佳的（65%）

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.