1/8-Predictors and Mechanisms of Conversion to Psychosis

1/8-转变为精神病的预测因素和机制

• 批准号: 7871117
• 负责人: TYRONE D CANNON
• 金额: $ 20.88万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7871117
• 关键词: Address; Adolescent; Affect; Affective; Age; Age of Onset; Algorithms; Antipsychotic Agents; Attention; Biological; Biological Markers; Brain; Candidate Disease Gene; Chronic; Clinical; DNA; DSM-IV; Data; Data Set; Deterioration; Development; Diagnostic; Disease; EP300 gene; Early Diagnosis; Economics; Electrophysiology (science); Elements; Enrollment; Epidemiology; Etiology; Family; Functional disorder; Funding; Future; Genetic; Genetic Predisposition to Disease; Genomics; Heterogeneity; Hormonal; Hormones; Hydrocortisone; Impairment; Incidence; Individual; Intervention; Knowledge; Life; Longitudinal Studies; Measures; Medial; Memory; Meta-Analysis; Methodology; National Institute of Mental Health; Neurobiology; Neurocognition; Neurocognitive; North America; Outcome; Paranoia; Pathway interactions; Patients; Performance; Persons; Phase; Population; Prevention; Prevention strategy; Preventive Intervention; Problem Solving; Process; Prospective Studies; Protocols documentation; Psychosocial Factor; Psychotic Disorders; RNA; Recruitment Activity; Research; Risk; Sample Size; Sampling; Schizophrenia; Series; Site; Societies; Stress; Structure; Subgroup; Syndrome; Temporal Lobe; Testing; Time; Work; base; deviant; endophenotype; executive function; follow-up; gray matter; help-seeking behavior; high risk; improved; instrument; interest; meetings; neuroimaging; neuromechanism; neurophysiology; prevent; programs; progression marker; prospective; psychosocial; repository; social

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.

精神分裂症和其他形式的精神病会影响大约3％的人口 通常是慢性和残疾。发病的峰值年龄在18-30岁之间，这是一生中最大的 生产年份已经开始。尽管遗传责任和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因素，主要是 未知。迄今 之所以可能，是因为大多数处于真正风险的人都无法在病态上识别。这阻碍了努力 预防。但是，风险确定方法的最新进展已实现可靠的身份证明 在1-2之内发展精神病的临床综合症的寻求帮助的人 年龄在20％-50％之间。这就是临床高风险人群现在可以追踪 前瞻性的精神病的发展和出现。但是，由于事件的低点 精神分裂症和临床高危病例中结果的异质性，单个站点研究不能 有效利用识别精神病的预测因素和机制的风险标准。 napls 创建了联盟来解决这个问题。北美的八个NIMH资助的地点研究前驱 使用常见前代评估仪器的患者合并了数据，以创建最大的样本 全球人（n = 291），其中35％在2年后转化为精神病。基线算法 生成数据，以约80％的阳性预测能力和40％的灵敏度预测精神病。在这个 修订的建议，我们描述了一项协作的前瞻性研究，我们将招募800例和400例 使用常见的，标准化的临床和神经生物学指标，可以在5年内进行适当的控制。目的 是收集具有足够尺寸和功能的样本，以严格测试对责任至关重要的样本和 大脑结构，电生理学，应力角的生物标志物领域的精神病发展， 和基因组学，以及前驱介绍和流行病学的临床领域。修订的建议 解决审稿人的关注点，包括将研究计划的整合和措施整合到统一中 框架。这些发现将增强我们通过 完善转化的预测指标，并扩展我们对潜在神经机制的理解。这样的 知识对于未来在早期发现，干预和预防精神病疾病的努力至关重要。防止精神分裂症和其他精神病可以挽救个人和家庭的巨大燃烧 对社会的苦难和经济损失。这个8个站点的项目旨在提高我们识别高风险的能力 发作之前的个体并查明神经生物学的变化，这是精神病的出现的基础 紊乱。这些努力对于制定有效的预防性干预策略至关重要 精神病。