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大约3%的人口， 通常是慢性的和致残的。发病的高峰年龄在18-30岁之间，发生在生命中最重要的时期。 富有成效的年份开始了。虽然遗传易感性和大脑发育异常是众所周知的， 精神分裂症和相关综合征的病因学和病理生理学在很大程度上是 未知迄今为止，对发病的前瞻性观察，即，从脆弱到混乱的转变， 这是因为大多数处于真正危险中的人不能在发病前被识别出来。这阻碍了 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。 患有精神病前期或“前驱”临床综合征的求助者， 年利率在20%-50%之间。因此，临床高风险人群现在可用于跟踪 精神病的发展和出现。然而，由于发病率低， 精神分裂症和临床高危病例结局的异质性，单中心研究不能 有效地利用风险标准来识别精神病的预测因子和机制。NAPLS 联盟的成立就是为了解决这个问题。北美八个NIMH资助的研究前驱症状的地点 患者使用共同的前驱评估工具汇总数据，以创建此类最大样本， 全球范围内的患者（N=291），其中35%在2年后转为精神病。基线的一种算法 产生了预测精神病的数据，阳性预测能力约为80%，灵敏度约为40%。在这 修订后的建议，我们描述了一个合作的前瞻性研究，我们将招募800例和400 使用常见的标准化临床和神经生物学措施进行5年的适当控制。目的 是收集具有足够大小和能力的样本，以严格测试对责任至关重要的元素， 在脑结构、电生理学、应激激素等生物标志物领域的精神病发展， 和基因组学，并在前驱表现和流行病学的临床领域。的订正提案 解决了审查者的关注，包括将研究计划和措施纳入统一的 框架.研究结果将加强我们识别高危人士的能力， 改进转化的预测因子，扩大我们对潜在神经机制的理解。等 知识对于今后早期发现、干预和预防精神病的努力至关重要。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 给社会带来的经济损失和痛苦。这个8个地点的项目旨在提高我们识别高风险 个人发病前，并查明神经生物学的变化，基础上出现的精神病 disorder.这些努力对于制定有效的预防性干预战略至关重要， 精神障碍

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.