Characterization of Prodromal Schizophrenia

描述(申请人提供)：精神分裂症的早期干预在研究和临床实践中都是一个越来越有影响力的运动，其基础是在疾病的前驱阶段开始的治疗可以预防精神病。然而，几乎没有长期的前瞻性信息可以用来了解前驱症状的性质、进展或真实结果。由于并不是所有符合既定标准的人实际上都会患上精神分裂症，因此仍然需要确定那些真正有可能患上以后疾病的人。这项研究旨在前瞻性地描述前驱症状的发展过程，并确定其哪些决定性症状预示着后来出现的精神病和精神分裂症。此外，这项研究将扩大结果的范围，超出精神病的预测，以强调精神分裂症所有阶段的严重功能障碍。因此，目前的要求是用5年时间大幅扩大和加强这项研究。拟议延续的主要目标包括：1)验证疾病进展的神经发育阶段模型；2)区分可用作特征标记的神经认知、行为和临床风险因素的“脆弱核心”；3)延长随访至4年，更准确地评估结果，重点放在功能障碍上；以及4)确定是否可以得出一个综合指数，准确预测哪些前驱受试者将转化为精神病。在第二阶段的过程中，总共将招募148名患者，并与作为第一阶段的一部分已经招募的152名参与者相结合。这将产生一个由300名前驱个体组成的组合样本--这不仅将具有相当大的统计能力，而且还代表了文献中最大的前驱样本之一。根据我们的发展战略，样本将被分为4个诊断阶段，每个亚组75名患者。此外，还将包括100名健康对照的比较样本。这一设计预计将为开发针对广泛结果的有效、特定阶段的干预措施提供必要的前瞻性证据基础。预防精神病仍然是一个非常长期的目标。

DESCRIPTION (provided by applicant): Early intervention for schizophrenia is an increasingly influential movement in both research and clinical practice, and is based on the notion that treatment initiated during the prodromal phase of illness may prevent psychosis. However, little long-term prospective information is available to understand the nature, progression, or true outcome of the prodrome. Since not all individuals meeting established criteria will actually develop schizophrenia, there remains a primary need to identify those at true risk for later illness. This study is designed to prospectively characterize the developmental course of the prodrome and to determine which of its defining symptoms predict later emerging psychosis and schizophrenia. Further, this study will expand the range of outcomes beyond prediction of psychosis, to emphasize the severe functional impairments that characterize all phases of schizophrenia. Thus, the current request is for 5 years to substantially expand and enhance the study. Major goals of the proposed continuation include: 1) to validate a neurodevelopmental stage model of illness progression; 2) to differentiate a "vulnerability core" of neurocognitive, behavioral and clinical risk factors that may serve as trait markers; 3) to lengthen follow-up to 4 years, to more accurately assess outcome, with a major new focus on functional disability, and 4) to establish whether a composite index can be derived that will accurately predict which prodromal subjects will convert to psychosis. A total of 148 patients will be recruited over the course of Phase II and be combined with 152 participants already recruited as part of Phase I. This will generate a combined sample of 300 prodromal individuals-which will not only have considerable statistical power but also represents 1 of the largest prodromal samples in the literature. Based on our developmental strategy, the sample will be divided into 4 diagnostic stages, with 75 patients in each subgroup. In addition, a comparison sample of 100 healthy controls will be included. This design is expected to provide the prospective evidence base essential to develop effective, stage-specific interventions targeting a broad spectrum of outcomes. Prevention of psychosis remains a very long-term goal.