8/8-Predictors and Mechanisms of Conversion to Psychosis

8/8-转变为精神病的预测因素和机制

基本信息

批准号：
8793697
负责人：
Scott W Woods
金额：
$ 20.89万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-30 至 2014-09-24
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8793697
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 Repository 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 Health 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 social

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：精神分裂症和其他形式的精神病会影响大约3％的人群，患有通常是慢性和残疾的疾病。发病的峰值年龄在18-30岁之间，就像人生生产最多的岁月一样。尽管遗传责任和脑发育异常是已知的因素，但精神分裂症和相关综合征的病因和病理生物学基本上是未知的。迄今为止，对发病的前瞻性观察，即，从脆弱性到无序的过渡是不可能的，因为大多数处于真正风险的人都无法审视。这阻碍了预防的努力。但是，风险确定方法的最新进展使人们能够可靠地识别患有精神病前或“前驱”临床综合症的寻求帮助者，他们在1 - 2年内以20％-50％的速度在1 - 2年内发展精神病。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。但是，由于精神分裂症的发生率低以及在临床高危病例中结果的异质性，因此单个部位研究无法有效利用风险标准在识别精神病的预测因素和机制方面。 NAPLS联盟的创建是为了解决这个问题。北美的八个由NIMH资助的地点使用常见的前瞻性评估仪器汇总数据来研究前驱患者，以创建全球此类此类人的最大样本（n = 291），其中35％在2年后转化为精神病。生成了基线数据的算法，以预测精神病，其阳性预测能力约为80％，灵敏度为40％。在这项修订的建议中，我们描述了一项协作的前瞻性研究，我们将使用常见的，标准化的临床和神经生物学指标在5年内招募800例和400个适当的对照。目的是收集具有足够大小和功率的样本，以严格测试对大脑结构，电生理学，应激激素和基因组学以及前驱动物学表现和流行病学的临床领域的生物标志物领域责任和发展至关重要的元素。修订后的提案解决了审稿人的担忧，包括将研究计划的整合和措施整合到统一的框架中。这些发现将增强我们通过完善转化率的预测以及扩展我们对基本神经机制的理解来确定即将到来精神病的高风险的人的能力。这种知识对于未来的早期发现，干预和预防精神病疾病至关重要。