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.

现在有相当多的证据表明，在精神分裂症的第一次发作中存在解剖病理学。 很少有研究针对了解这些解剖缺陷及其纵向 病程可用于预测治疗反应、神经心理和功能结果。 措施。在病程早期识别对标准无反应的患者 抗精神病药物治疗可能对药物干预和治疗策略产生重大影响 改善后续预后。精神分裂症治疗反应的神经生物学预测因素有 然而，没有很好的定义，这种现象没有明确的神经生物学基础，尽管有缺陷 在大脑中，灰质已被牵连。此外，最近的经验和理论工作表明， 脑白质缺陷可能是精神分裂症抗精神病药物无反应的一个促成因素。 精神分裂症的神经生物学预测因素的研究在很大程度上是由于缺乏 从受控临床试验中招募患者并测试有关反应的假设。我们的 初步数据表明，通过皮质表面标测评估的前额叶灰质缺陷 方法：预测首发精神分裂症患者的治疗反应。其他初步数据 提示额颞区较低的分数各向异性，如通过扩散张量成像评估 与这些患者的治疗无反应有关。在本研究中，我们建议扫描一个 独一无二的75例抗精神病药物--NATVE，首发精神分裂症患者。患者将被抽出 来自NIMH赞助的(2R01-MH60004)利培酮与 阿立哌唑，随后作为CIDAR临床的一部分，在对照治疗下进行定期评估 算法一年。本研究的具体目的是：(1)确定大脑皮层 首发精神分裂症患者灰质体积/密度和白质分数各向异性 12周随机临床试验后和52周后的治疗反应/结果 对照治疗；以及(2)检测灰质体积/密度和白质分数的变化 首发患者在12周随机临床试验和52周对照试验中的各向异性 治疗与治疗反应/结果的关系。最初对这些异常的识别 疾病发作可能有助于确定脆弱性的指标，这可能会导致早期改善 精神分裂症高危个体的识别。