MR Imaging Predictors of Response & Outcome in First Episode Schizophrenia

MR 成像反应预测因子

• 批准号: 8065451
• 负责人: PHILIP R SZESZKO
• 金额: $ 18.91万
• 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: 2010-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8065451
• 关键词: Algorithms; Anatomy; Anisotropy; Antipsychotic Agents; Brain; Clinical; Clinical assessments; Controlled Clinical Trials; Data; Defect; Diffusion Magnetic Resonance Imaging; Double-Blind Method; Drug Exposure; Exposure to; Functional disorder; Heterogeneity; Honey; Individual; Intervention; Investigation; Knowledge; Lead; Left; Longitudinal Studies; Magnetic Resonance Imaging; Maps; Methods; Modeling; Neurobiology; Outcome; Outcome Measure; Pathology; Patients; Randomized; Randomized Clinical Trials; Recruitment Activity; Research; Risk; Risperidone; Sample Size; Scanning; Schizophrenia; Study models; Surface; Testing; Translating; Work; aripiprazole; base; clinical care; density; experience; first episode schizophrenia; functional outcomes; gray matter; improved; longitudinal course; neuroimaging; neuropsychological; outcome forecast; prospective; response; treatment response; week trial; white matter

There is now considerable evidence that anatomic pathology is present at the first episode of schizophrenia. Little research has been directed at understanding whether these anatomic deficits and their longitudinal course can be used to predict treatment response and neuropsychological and functional outcome measures. The identification of patients early in the course of illness who are nonresponsive to standard antipsychotic treatment could have significant implications for pharmacologic intervention and strategies for improving subsequent prognosis. Neurobiological predictors of treatment response in schizophrenia have not been well defined, however, and this phenomenon has no clear neurobiological basis, although a defect in the brain gray matter has been implicated. Moreover, recent empirical and theoretical work suggests that a defect in the brain white matter may be a contributing factor to antipsychotic nonresponse in schizophrenia. The investigation of neurobiological predictors in schizophrenia has been limited in large part due to the lack of controlled clinical trials from which to recruit patients and test hypotheses regarding response. Our preliminary data suggest that prefrontal gray matter deficits, as assessed via cortical surface mapping methods, predict treatment response in patients with first episode schizophrenia. Additional preliminary data suggest that lower fractional anisotropy, as assessed via diffusion tensor imaging, in frontotemporal regions is associated with treatment nonresponse in these patients. In the present study we propose scanning a unique group of 75 antipsychotic drug-naTve, first episode schizophrenia patients. Patients will be drawn from an NIMH-sponsored (2R01-MH60004) double-blind randomized 12-week trial of risperidone vs. aripiprazole, and followed with regular assessments under controlled treatment as part of the CIDAR clinical algorithm for one year. The specific aims of this study are to: (1) determine the relationship between cortical gray matter volume/density and white matter fractional anisotropy in first episode patients with schizophrenia and treatment response/outcome following the 12 week randomized clinical trial and after 52 weeks of controlled treatment; and (2) examine changes in gray matter volume/density and white matter fractional anisotropy in first episode patients over the 12 week randomized clinical trial and after 52 weeks of controlled treatment in relationship to treatment response/outcome. The identification of these abnormalities at the first episode of illness may be useful for identifying indicators of vulnerability, which may lead to improved early dentification of individuals at risk for schizophrenia.

现在有大量证据表明，精神分裂症的第一集存在解剖病理学。 很少有研究旨在了解这些解剖缺陷及其纵向是否 课程可用于预测治疗反应以及神经心理学和功能结果 措施。疾病早期对患者的鉴定，对标准无反应 抗精神病药物治疗可能对药理学干预和策略产生重大影响 改善随后的预后。精神分裂症治疗反应的神经生物学预测指标 然而，没有得到很好的定义，这种现象没有明确的神经生物学基础，尽管缺陷 在脑灰质中已被牵涉。此外，最近的经验和理论工作表明 脑白质缺陷可能是导致精神分裂症抗精神病药无反应的因素。 精神分裂症中神经生物学预测因子的研究在很大程度上受到了限制，这是由于缺乏 从中招募患者和关于反应的假设的对照临床试验。我们的 初步数据表明，前额叶灰质缺陷，如通过皮质表面映射评估 方法，预测第一发精神分裂症患者的治疗反应。其他初步数据 建议通过扩散张量成像评估，较低的分数各向异性在额颞区 与这些患者的治疗无反应有关。在本研究中，我们建议扫描 独特的75种抗精神病药，第一事件精神分裂症患者。将吸引患者 来自NIMH赞助的（2R01-MH60004）双盲随机12周的Risperidone vs。 Aripiprazole，然后在受控治疗中进行定期评估，作为CIDAR临床的一部分 算法一年。这项研究的具体目的是：（1）确定皮质之间的关系 灰质体积/密度和白质分数各向异性在精神分裂症患者中 和治疗反应/结果在12周后期的临床试验之后以及52周后 受控治疗； （2）检查灰质体积/密度和白质分数的变化 在12周的随机临床试验和52周后，第一集患者的各向异性患者的各向异性 与治疗反应/结果的关系。第一次识别这些异常 疾病发作可能有助于识别脆弱性指标，这可能会导致早期改善 牙齿的牙齿滋养患有精神分裂症风险的人。