1/8-Predictors and Mechanisms of Conversion to Psychosis

精神分裂症和其他形式的精神病影响着大约3%的患有精神障碍的人口 通常是慢性的和致残的。发病高峰年龄在18-30岁之间，恰好发生在生命中的最高年龄 富有成效的几年开始了。尽管遗传易感性和大脑发育异常是已知的 精神分裂症和相关综合征的病因和病理生理在很大程度上 未知。迄今为止，对发病的前瞻性观察，即从脆弱到无序的转变，还没有 这是可能的，因为大多数真正有风险的人不能在发病前被识别出来。这阻碍了这些努力。 在预防方面。然而，风险确定方法的最新进展使可靠的识别成为可能 有精神病前期或“前驱症状”临床症状的求助人士在1-2个月内发展成精神病 年利率在20%-50%之间。因此，临床高危人群现在可以进行跟踪。 前瞻性地预测精神病的发展和出现。然而，由于发病率较低， 精神分裂症和临床高危病例结果的异质性，单一地点研究不能 有效地利用风险标准来确定精神病的预测因素和机制。NAPLS 联合体就是为了解决这个问题而成立的。NIMH资助的北美八个研究前驱现象的网站 使用常见前驱症状评估工具的患者汇集数据以创建此类样本中的最大样本 全世界(N=291)人，其中35%在两年后转变为精神病。一种基线解算算法 生成的数据预测精神病的阳性预测力约为80%，敏感度约为40%。在这 修订后的提案，我们描述了一项合作的前瞻性研究，我们将招募800名病例和400名患者 使用常见的标准化临床和神经生物学措施，在5年内进行适当的控制。其目的是 收集具有足够大小和能力的样本，以严格测试对感染和感染 精神病在脑结构、电生理、应激激素、 和基因组学，以及在前驱症状和流行病学的临床领域。修订后的提案 解决审查者的关切，包括将研究计划和措施纳入统一的 框架。这些发现将增强我们识别即将发生精神病的高危人群的能力，方法是 提炼转换的预测因素，并扩大我们对潜在神经机制的理解。是这样的 知识对于今后在早期发现、干预和预防精神障碍方面的努力至关重要。预防精神分裂症和其他精神病可以减轻个人和家庭的巨大负担 给社会带来痛苦和经济损失。此8站点项目旨在提高我们识别高风险的能力 并准确定位精神病患者出现的神经生物学变化 无序。这些努力对于制定有效的预防干预战略至关重要。 精神错乱。

Schizophrenia and other forms of psychosis affect approximately 3% of the population with a disorder that is usually chronic and disabling. The peak age of onset is between ages 18-30, occurring just as life's most productive years are beginning. Although genetic liability and abnormal brain development are known contributing factors, the etiology and pathophysiology of schizophrenia and related syndromes is largely unknown. To date, prospective observation of onset, i.e., the transition from vulnerability to disorder, has not been possible because most persons at true risk cannot be identified premorbidly. This has hampered efforts at prevention. However, recent progress in risk ascertainment methodology has enabled reliable identification of help-seeking persons with pre-psychotic or "prodromal" clinical syndromes who develop psychosis within 1-2 years at rates between 20%-50%. Thus, clinical high-risk populations are now available for tracking prospectively the development and emergence of psychosis. However, because of the low incidence of schizophrenia and the heterogeneity of outcomes in clinical high-risk cases, single site studies cannot efficiently exploit the risk criteria in identifying predictors and mechanisms of psychosis. The NAPLS consortium was created to solve this problem. Eight NIMH-funded sites in North America studying prodromal patients using a common prodromal assessment instrument pooled data to create the largest sample of such persons worldwide (N=291), 35% of whom converted to psychosis after 2¿ years. An algorithm of baseline data was generated predicting psychosis with about 80% positive predictive power and 40% sensitivity. In this revised proposal, we describe a collaborative prospective study for which we will recruit 800 cases and 400 appropriate controls over 5 years using common, standardized clinical and neurobiological measures. The aim is to collect a sample with sufficient size and power to rigorously test elements critical to the liability for and development of psychosis in the biomarker domains of brain structure, electrophysiology, stress hormones, and genomics, and in the clinical domains of prodromal presentation and epidemiology. The revised proposal addresses reviewers' concerns, including the integration of the research plan and measures into a unifying framework. The findings will enhance our ability to identify persons at high risk for imminent psychosis, by refining predictors of conversion, and expanding our understanding of the underlying neural mechanisms. Such knowledge is critical for future efforts at early detection, intervention and prevention of psychotic disorders. Preventing schizophrenia and other psychoses could relieve an enormous burden of personal and family suffering and economic losses to society. This 8-site project aims to increase our ability to identify high-risk individuals prior to onset and to pinpoint neurobiological changes that underlie the emergence of a psychotic disorder. These efforts are critical to the development of effective preventative intervention strategies for psychotic disorders.