Diffusion Tensor Imaging in First-Episode Schizophrenia

描述（由申请人提供）：大量研究表明，精神分裂症的特征在于额颞区的缺陷，越来越多的证据表明，该整合系统的脑白色物质的缺陷对现象学至关重要。扩散张量成像（DTI）可用于量化水自扩散的方向性和相干性，从而允许检查体内的白色物质微观结构。精神分裂症的初步DTI研究表明，与健康志愿者相比，慢性患者存在白色病变，但关于解剖病理学的特异性，特别是在疾病早期和抗精神病药物治疗前，留下了重大的未回答的问题。此外，迄今为止，很少有工作是针对了解这些白色物质赤字的功能意义。通过K 01机制，PI已完成初步研究，证明与健康志愿者相比，首发精神分裂症患者的中额和上级颞白色物质、扣带束和钩束的各向异性分数（FA）较低或迹线较高。需要更大的样本来确认这些初步研究结果，辨别其神经心理学和临床相关性，并研究它们如何与包括额颞系统的脑容量测量相关。此外，最近的经验和理论研究表明，大脑白色物质的缺陷可能是精神分裂症抗精神病药物无反应的一个因素，但这一领域的研究一直受到缺乏对照临床试验招募患者和测试假设的限制。我们建议扫描一组独特的60名首次使用抗精神病药物的首发精神分裂症患者，这些患者将参加NIMH赞助的为期12周的利培酮与阿立哌唑双盲临床试验，该试验将在我们的精神分裂症高级干预和服务研究中心的支持下进行，并招募60名年龄和性别匹配的健康志愿者。本研究的具体目的是：（1）确定与健康志愿者相比，首次使用抗精神病药物的精神分裂症患者白色微结构病理的区域特异性;（2）确定与健康志愿者相比，患者异常白色微结构的功能相关性;（3）与健康志愿者相比，检查患者额叶白色物质显微结构与海马体积之间的关系;（4）确定脑白色区域预测首次发作精神分裂症患者的抗精神病药物初治的治疗反应。这些异常的识别在第一次发病的疾病可能是有用的识别指标的脆弱性，这可能会导致改善早期识别个人的精神分裂症的风险。

DESCRIPTION (provided by applicant): Considerable research suggests that schizophrenia is characterized by a defect in frontotemporal regions with increasing evidence that a defect in the brain white matter of this integrated system is critical to phenomenology. Diffusion tensor imaging (DTI) can be used to quantify the directionality and coherence of water self-diffusion allowing the examination of white matter microstructure in-vivo. Initial DTI studies in schizophrenia demonstrated that white matter pathology is present in chronic patients compared to healthy volunteers, but left major unanswered questions regarding the specificity of anatomic pathology, especially early in the illness and prior to antipsychotic treatment. Moreover, little work to date has been directed at understanding the functional significance of these white matter deficits. Through the K01 mechanism the PI has completed preliminary studies demonstrating lower fractional anisotropy (FA) or higher trace in the middle frontal and superior temporal white matter, cingulum bundle and uncinate fasciculus in first-episode schizophrenia patients compared to healthy volunteers. Larger samples are required to confirm these initial findings, discern their neuropsychological and clinical correlates and to examine how they relate to brain volumetric measures comprising the frontotemporal system. 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, but research in this area has been limited by the lack of controlled clinical trials from which to recruit patients and test hypotheses. We propose scanning a unique group of 60 antipsychotic drug-naive, first-episode schizophrenia patients to be enrolled in an NIMH- sponsored double-blind 12 week clinical trial of risperidone versus aripiprazole to be conducted under the aegis of our Advanced Center for Intervention and Services Research in Schizophrenia and 60 age- and sex-matched healthy volunteers. The specific aims of this study are to: (1) determine the regional specificity of white matter microstructural pathology in antipsychotic drug-naive first-episode patients with schizophrenia compared to healthy volunteers using DTI; (2) determine the functional correlates of abnormal white matter microstructure in patients compared to healthy volunteers; (3) examine the relationship between frontal lobe white matter microstructure and hippocampal volume in patients compared to healthy volunteers; (4) identify brain white matter regions that predict treatment response in antipsychotic drug-naive patients with first-episode schizophrenia. 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 identification of individuals at risk for schizophrenia.