MR Imaging Predictors of Response & Outcome in First Episode Schizophrenia

现在有相当多的证据表明，解剖病理学是目前在第一次发作的精神分裂症。 很少有研究旨在了解这些解剖缺陷及其纵向 病程可用于预测治疗反应以及神经心理和功能结局 措施在病程早期识别对标准治疗无反应的患者 抗精神病药物治疗可能对药物干预和治疗策略有重要意义。 改善后续预后。精神分裂症治疗反应的神经生物学预测因子 然而，这种现象没有得到很好的定义，并且这种现象没有明确的神经生物学基础，尽管这是一种缺陷。 大脑灰质中的神经元也受到了牵连此外，最近的经验和理论工作表明， 脑白色物质的缺陷可能是精神分裂症中抗精神病药物无反应的一个促成因素。 精神分裂症神经生物学预测因子的研究在很大程度上受到限制， 对照临床试验，从中招募患者和测试有关反应的假设。我们 初步数据表明，前额叶灰质缺陷，通过皮质表面映射评估， 方法，预测首发精神分裂症患者的治疗反应。其他初步数据 表明额颞区较低的各向异性分数，如通过扩散张量成像所评估的， 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 一组75名首次使用抗精神病药物的首发精神分裂症患者。患者将被抽取 来自NIMH申办的（2 R 01-MH 60004）利培酮与 阿立哌唑，并随后在对照治疗下进行定期评估，作为CIDAR临床研究的一部分。 算法一年。本研究的具体目的是：（1）确定皮层与神经元之间的关系， 首发精神分裂症患者灰质体积/密度和白色物质分数各向异性的研究 12周随机临床试验后和52周后的治疗反应/结果 对照治疗;和（2）检查灰质体积/密度和白色物质分数的变化 在12周随机临床试验期间和52周对照试验后， 治疗与治疗反应/结果的关系。这些异常的识别首先 疾病发作可能有助于确定脆弱性指标，这可能导致改善早期 识别有精神分裂症风险的个体。

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.