Neuroscience-Guided Cognitive Remediation in Adolescents at Risk for Psychosis

描述(由申请人提供)：该项目的目的是通过使青少年和年轻人的认知功能障碍正常化，以拯救易患精神病的大脑，这些青少年和年轻人是发展成第一次精神病发作的高风险人群。我们将对40名超高风险(UHR)青少年和16-25岁的过渡年龄青少年进行80小时(16周)的密集计算机化神经适应认知训练，他们符合精神分裂症“前驱综合征”的诊断标准。受试者将从加利福尼亚州的两个研究地点(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非常危险的年轻人的影响将与年龄和性别匹配的健康对照受试组获得的效果进行比较，并与40名接受电脑游戏“主动控制”的匹配组的UHR年轻人获得的效果进行比较。这一方法得到了我们目前由NIMH资助的基于神经可塑性的认知修复成人慢性精神分裂症患者随机对照试验的数据的支持，在60小时的强化训练后，处理速度、工作记忆以及言语学习和记忆方面的非常显著的改善是显而易见的。来自三名参加了40小时训练练习的UHR青少年的初步“开放标签”数据显示，在注意力/工作记忆、情景记忆和执行功能方面，平均z分数改善了0.9分、0.7分和1.1分。因此，我们的总体目标是：1)使用实验神经科学的原理来利用大脑可塑性的机制和纠正UHR个体皮质中的异常信息处理；2)预防或减轻精神障碍的发生，并改善这些青少年和过渡年龄青年的适应功能。公共卫生叙述：这项研究的目的是使用神经科学指导的计算机化训练练习来补救年轻人出现的思维困难，这些年轻人有很高的精神病发作风险。如果这一干预措施被证明是有效的，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，并可能降低患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.