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

• 批准号: 7693812
• 负责人: Scott W Woods
• 金额: $ 59.3万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 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/7693812
• 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; public health relevance; repository; social

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）：约 3% 的人口患有精神分裂症和其他形式的精神病，这些疾病通常是慢性且致残的。发病高峰年龄在 18 岁至 30 岁之间，此时正值生命中生产力最高的时期开始。尽管遗传倾向和大脑发育异常是已知的促成因素，但精神分裂症及相关综合征的病因学和病理生理学在很大程度上尚不清楚。迄今为止，对发病情况（即从脆弱性到疾病的转变）的前瞻性观察尚不可能，因为大多数处于真正风险的人无法在病前识别。这阻碍了预防工作。然而，风险确定方法的最新进展已经能够可靠地识别患有精神病前期或“前驱期”临床综合征的寻求帮助者，这些人在 1-2 年内以 20%-50% 的比率发展为精神病。因此，临床高危人群现在可用于前瞻性追踪精神病的发展和出现。然而，由于精神分裂症的发病率低以及临床高风险病例结果的异质性，单中心研究无法有效利用风险标准来识别精神病的预测因素和机制。 NAPLS 联盟就是为了解决这个问题而创建的。北美 NIMH 资助的 8 个研究中心使用通用的前驱评估工具汇总数据，创建了全球此类患者的最大样本 (N=291)，其中 35% 的患者在 2 年后转变为精神病。生成的基线数据算法可预测精神病，其阳性预测能力约为 80%，敏感性为 40%。在这份修订后的提案中，我们描述了一项合作前瞻性研究，我们将在 5 年内使用常见的标准化临床和神经生物学措施招募 800 例病例和 400 名适当对照。目的是收集足够大小和功效的样本，在大脑结构、电生理学、应激激素和基因组学的生物标志物领域，以及前驱表现和症状的临床领域，严格测试对精神病的责任和发展至关重要的元素。流行病学。修订后的提案解决了审稿人的担忧，包括将研究计划和措施纳入统一框架。这些发现将通过完善转变的预测因素并扩大我们对潜在神经机制的理解，增强我们识别即将发生精神病的高风险人群的能力。这些知识对于未来早期发现、干预和预防精神障碍的努力至关重要。公共卫生相关性：预防精神分裂症和其他精神病可以减轻个人和家庭痛苦以及社会经济损失的巨大负担。这个包含 8 个地点的项目旨在提高我们在发病前识别高风险个体的能力，并查明精神障碍出现背后的神经生物学变化。这些努力对于制定有效的精神障碍预防干预策略至关重要。