Neuroscience-Guided Cognitive Remediation in Adolescents at Risk for Psychosis

项目描述（由申请人提供）：本项目旨在通过使首次精神病发作高风险的青少年和年轻人的认知功能障碍正常化，“拯救”易患精神病的大脑。我们将对40名年龄在16-25岁、符合精神分裂症“前驱综合征”诊断标准的超高风险（UHR）青少年和过渡年龄青年进行80小时（16周）的强化计算机化神经适应性认知训练。受试者将从加州的两个研究地点（加州大学旧金山分校和加州大学戴维斯分校）合作抽取。这种基于神经可塑性的认知修复对这些高危青少年的影响将与年龄和性别匹配的健康对照对象组的效果进行比较，并与40名UHR青少年进行电脑游戏“主动控制”条件的匹配组的效果进行比较。这种方法得到了nimh资助的随机对照试验数据的支持，该试验对成年慢性精神分裂症患者进行了基于神经可塑性的认知修复，在经过60小时的强化训练后，处理速度、工作记忆、语言学习和记忆都有了显著的改善。初步的“开放标签”数据来自三名参加了40小时训练的UHR青少年，结果显示，注意力/工作记忆的平均z得分提高了0.9，情景记忆提高了0.7，执行功能提高了1.1。因此，我们的总体目标是：1)利用实验神经科学的原理来利用大脑可塑性机制并纠正UHR个体皮层中的异常信息处理；2)预防或减轻这些青少年和过渡年龄青少年的精神病发作，改善其适应功能。公共卫生叙述：本研究的目的是使用神经科学指导的计算机化训练练习来纠正发生在精神病发作风险很高的年轻人中的思维困难。如果这种干预被证明是有用的，它将为年轻人提供一种安全且易于应用的非药物治疗方法，并且可能降低严重精神疾病的风险并改善长期结果。

DESCRIPTION (provided by applicant): The purpose of this project is to "rescue" the psychosis-prone brain by normalizing the cognitive dysfunction of adolescents and young adults who are at high risk for developing a first psychotic episode. We will apply 80 hours (16 weeks) of intensive computerized neuroadaptive cognitive training exercises to 40 ultra high-risk (UHR) adolescents and transitional age youth, ages 16-25, who meet diagnostic criteria for the "prodromal syndrome" in schizophrenia. Subjects will be drawn collaboratively from two research sites in California (UCSF and UC Davis). The effects of this neuroplasticity-based cognitive remediation on these very high-risk youth will be compared to the effects obtained in an age- and sex- matched group of healthy comparison subjects, and to the effects obtained in a matched group of 40 UHR youth who undergo a computer games "active control" condition. This approach is supported by data from our current NIMH-funded randomized controlled trial of neuroplasticity-based cognitive remediation in adult patients with chronic schizophrenia, where highly significant improvements in processing speed, working memory, and verbal learning and memory, are apparent after 60 hours of intensive training. Preliminary "open-label" data from three UHR adolescents who participated in 40 hours of training exercises showed mean z-score improvements of 0.9 on attention/working memory, 0.7 on episodic memory, and 1.1 on executive functioning. Our overall aims are thus to: 1) Use principles from experimental neuroscience to harness mechanisms of brain plasticity and correct aberrant information processing in the cortex of UHR individuals; 2) Prevent or attenuate the onset of psychotic disorder and improve adaptive functioning in these adolescents and transitional age youth. PUBLIC HEALTH NARRATIVE: The purpose of this study is to use neuroscience-guided computerized training exercises to remediate the thinking difficulties that occur in young people who are at very high risk of developing a psychotic episode. If this intervention proves useful, it will provide a non- pharmacological treatment approach for young people that is safe and easy to apply, and that may reduce the risk for serious mental illness as well as improve long-term outcome.