6/8-Predictors and Mechanisms of Conversion to Psychosis

6/8-转变为精神病的预测因素和机制

基本信息

批准号：
7529854
负责人：
KRISTIN S. CADENHEAD
金额：
$ 35.39万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
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 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7529854
关键词：
Address Adolescent Adult Advisory Committees Affect Affective Age Age of Onset Algorithms American Antipsychotic Agents Appendix Area Arts Attention Award Biological Biological Assay Biological Markers Biology Brain Calibration California Candidate Disease Gene Chronic Classification Clinical Clinical assessments Collaborations Commit Consensus Core Facility DNA DSM-IV Data Data Set Depth Deterioration Development Diabetes Mellitus Diagnosis Diagnostic Disease EP300 gene Early Diagnosis Early Intervention Economics Electrophysiology (science)Elements Enrollment Ensure Epidemiology Etiology Evaluation Family Family history of Functional disorder Funding Future Genetic Genetic Polymorphism Genetic Predisposition to Disease Genome Genomics Goals Grant HPSE gene Heart Diseases Heterogeneity Hormonal Hormones Hospitals Hydrocortisone Image Impaired cognition Impairment Incidence Individual Influentials Information Networks International Intervention Investigation Knowledge Laboratories Laboratory Procedures Life Light Literature Longitudinal Studies Los Angeles Measures Medial Memory Messenger RNA Meta-Analysis Methodology Methods Modeling Monitor National Institute of Mental Health Natural History Neurobiology Neurocognition Neurocognitive Neurocognitive Deficit Neuropsychology North America North Carolina Numbers Occupational Onset of illness Outcome Paper Paranoia Pathway interactions Patients Performance Persons Phase Policies Population Postdoctoral Fellow Preparation Prevention Prevention intervention Prevention strategy Preventive Intervention Problem Solving Process Productivity Prospective Studies Protocols documentation Psychopathology Psychosocial Factor Psychotic Disorders Public Health Publications Publishing RNA Range Rate Recruitment Activity Reporting Request for Applications Research Research Personnel Retrospective Studies Risk Risk Factors Role Sample Size Sampling Schizophrenia Science Score Seminal Series Site Societies Staging Stress Structure Subgroup Symptoms Syndrome System Temporal Lobe Testing Thinking Time Traction Training Twin Studies Universities Visit Walkers Wood material Work affective psychoses base career cluster computing deviant endophenotype executive function experience follow-up genetic association genome wide association study gray matter help-seeking behavior hypothalamic-pituitary-adrenal axis image processing improved indexing instrument interest lymphoblastoid cell line member neuroimaging neuromechanism neurophysiology neuropsychological prevent programs prospective psychogenetics psychosocial repository size social social cognition symposium trait treatment effect

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. PUBLIC HEALTH RELEVANCE: 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.

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。公共卫生相关性：预防精神分裂症和其他精神病可能会减轻个人和家庭苦难以及对社会的经济损失的巨大负担。这个8个站点的项目旨在提高我们在发作之前识别高风险个体的能力，并确定神经生物学的变化，这是精神病疾病出现的基础。这些努力对于制定有效的精神疾病预防干预策略至关重要。