Project 1 ACISR

项目1 ACISR

• 批准号: 8110777
• 负责人: CHRISTOPH U CORRELL
• 金额: $ 7.66万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-27 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8110777
• 关键词: Adherence; Adolescent; Adverse effects; American; Anti-Anxiety Agents; Antidepressive Agents; Antipsychotic Agents; Area; Attenuated; Biological Process; Brain; Chronic; Clinical Research; Data; Development; Developmental Delay Disorders; Disease; Early identification; Early treatment; Fluoxetine; General Population; Generations; Goals; Incidence; Incipient Schizophrenia; Individual; Intervention; Intervention Studies; Lead; Longitudinal Studies; Masks; Mediating; Medicine; Mood stabilizers; Neurodevelopmental Disorder; Outcome; Patients; Personal Satisfaction; Pharmaceutical Preparations; Phase; Physicians; Pilot Projects; Prevalence; Prevention; Preventive Intervention; Psychotic Disorders; Randomized; Recurrent disease; Relapse; Research; Retrospective Studies; Risk; Role; Safety; Sampling; Schizophrenia; Severities; Symptoms; Time; Wood material; Work; aged; aripiprazole; base; clinically relevant; cohort; design; first episode schizophrenia; functional decline; functional outcomes; gray matter; high risk; hypnotic; improved functioning; open label; prevent; prodromal psychosis; programs; protective effect; psychopharmacologic; symptomatic improvement; treatment response

Early Recognition and Prevention During the Psychotic Prodrome. After more than five decades of increasingly refined psychopharmacologic developments, schizophrenia has remained one of the most severe and disabling disorders in medicine. Since interventions after a first schizophrenia episode have not been able to alter the generally chronic and relapsing disease course (Robinson et al. 2004), eariy intervention and prevention of schizophrenia are a vital goal. Initial, retrospective studies that demonstrated presence of a symptomatic prepsychotic illness phase of clinically relevant severity and duration (Hafner et al. 1999) provided the practical basis for early identification efforts. Several lines of evidence further supported the potential utility of eariy interventions for the schizophrenia prodrome. These include an increasing appreciation that schizophrenia is a neurodevelopmental disorder characterized by early developmental delays and problems, and that is further associated with a significant functional decline and brain morphological changes (Correll and Kane 2004; Sawa and Snyder, 2002; Woods 1998). Moreover, the duration of untreated psychosis (Marshall et al. 2005), and number of relapses have been associated with decreased grey matter and worse functional outcomes, even after controlling for potentially relevant confounders (Perkins et al. 2005). Importantly, brain morphological changes have also been demonstrated during the transition from prodromal psychosis to full blown psychosis (Pantelis et al. 2003), suggesting that early intervention may be a potential vehicle to effectively interrupt biological processes involved in the development of psychosis and its adverse functional consequences. Prodromal schizophrenia research conducted over the past ten years at our Center and others has further consolidated the evidence that eariy identification and intervention studies during the schizophrenia prodrome are possible. Eariy recognition programs have identified high risk samples with conversion rates to psychosis between 10 and 40% over one to two years (Yung et al. 2008). In the largest study to date by the North American Prodromal Longitudinal Study (NAPLS) group of which Dr. Cornblatt at our Center is one of the PIs, a conversion rate of 35.3% over 2.5 years was reportecl (Cannon et al. 2008). These conversion rates to psychosis are 10-40 times the prevalence rate observed in the general population and far greater than the expected incidence rate during such a brief time period (Eaton 1999).

精神病前驱症状的早期识别和预防。经过50多年日益完善的精神药理学发展，精神分裂症仍然是医学上最严重和最致残的疾病之一。由于首次精神分裂症发作后的干预不能改变通常的慢性和复发性疾病进程（罗宾逊et al.2004），因此精神分裂症的早期干预和预防是至关重要的目标。最初的回顾性研究证明存在具有临床相关严重程度和持续时间的症状性精神病前期（Hafner et al. 1999），为早期识别工作提供了实践基础。一些证据进一步支持早期干预对精神分裂症前驱症状的潜在效用。其中包括人们越来越认识到， 精神分裂症是一种神经发育障碍，其特征在于早期发育延迟和问题，并且还与显著的功能下降和脑形态变化相关（Correll和 Kane 2004; Sawa和Snyder，2002; Woods 1998）。此外，未治疗精神病的持续时间（马歇尔et al. 2005）和复发次数与灰质减少和功能结局较差相关，即使在控制了潜在相关混杂因素后也是如此（Perkins et al. 2005）。重要的是，在从前驱精神病向完全发作的精神病转变期间也证明了脑形态学变化（Pantelis等人，2003），这表明早期干预可能是有效中断精神病发展及其不良功能后果所涉及的生物学过程的潜在手段。 在过去的十年里，在我们中心和其他人进行的前驱精神分裂症研究进一步巩固了在精神分裂症前驱症状期间进行早期识别和干预研究是可能的证据。早期的识别程序已经识别出高风险样本，在一到两年内转化为精神病的比率在10%到40%之间（Yung等人，2008）。在北美前驱期纵向研究（NAPLS）组迄今为止最大的研究中，我们中心的Cornblatt博士是其中一名PI，2.5年内的转换率为35.3%（Cannon等人，2008）。这些转化为精神病的比率是在一般人群中观察到的患病率的10-40倍，并且远远高于在如此短的时间段内的预期发病率（Eaton 1999）。