LONGITUDINAL NEUROIMAGING OF FIRST EPISODE SCHIZOPHRENIA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 第一代神经影像研究表明，解剖病理出现在精神分裂症的第一个发作(FE)，但留下了关于最初的病理及其纵向过程的主要悬而未决的问题。迫切需要答案来区分反映静止性脑病的缺陷和那些随着疾病进展的缺陷。大多数知识来自对慢性患者的横断面研究，但有证据表明，FE患者的病理不那么严重，可能存在与疾病相关的恶化。现在还怀疑一些抗精神病药物(APD)会影响大脑结构。这些发现突显了研究首发患者的必要性，从而能够准确地识别不能反映治疗或长期疾病影响的病理。这些发现进一步指出，有必要进行足够长时间的纵向随访，以期发生解剖学变化和相关的功能变化。新的研究还必须包括对治疗的充分控制和对营养状况的评估，以帮助区分最初和正在进行的与疾病相关的病理与与疾病无关的因素。为了能够与当前的实践相关联，必须评估接受新型APDS作为一线治疗的患者的大脑结构和结构-功能关系的变化。这项拟议的研究使用了磁共振成像(MRI)方法，在一个独特的样本中使用了首发抗精神病药物的患者(N=116)和人口统计学上匹配的健康志愿者(N=84)，他们正在参与一项目前由NIMH支持的研究。患者将随机接受三种新的APDS(奥氮平、利培酮或齐拉西酮)中的一种一线治疗，并进行为期3年的密集跟踪，进行广泛的临床、神经认知和功能结果评估。在治疗前、对照治疗16周后和3年后，将进行多个采集序列的MRI检查。将使用现有的和创新的形态计量学分析方法，能够详细绘制与组差异、纵向变化和功能指数相关的神经解剖变异图。所获得的数据将对区分初始和正在进行的解剖病理学，以及明确初始和正在进行的病理过程与多维反应模式和长期结果的关系具有重要意义。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The first generation of neuroimaging studies showed that anatomic pathology is present at the first episode (FE) of schizophrenia but left major unanswered questions about the initial pathology and its longitudinal course. Answers are critically needed to distinguish deficits reflecting static encephalopathy from those that progress with the illness. Most knowledge comes from cross-sectional studies of chronic patients, but evidence suggests that pathology is less severe in FE patients, and that there may be illness-associated deterioration. It is now suspected also that some antipsychotic drugs (APDs) affect brain structure. These findings highlight the need to study first episode patients, enabling accurate identification of pathology that cannot reflect treatment or long-term illness effects. The findings further point to the need for longitudinal follow-up of sufficient duration that anatomic changes and related functional changes can be expected to occur. New research must also include adequate control over treatments and assessments of nutritional status to help distinguish initial and ongoing illness-related pathologies from factors unrelated to the illness. To enable relevance to current practice, changes in brain structure and structure-function relations must be evaluated in patients receiving novel APDs as first-line treatments. The proposed research uses magnetic resonance imaging (MRI) methods in a unique sample of antipsychotic-na¿ve, first-episode patients (N = 116), and demographically matched healthy volunteers (N = 84), who are participating in a study now supported by the NIMH. Patients will be randomized to first-line treatment with one of three new APDs (olanzapine, risperidone, or ziprasidone), and followed intensively for 3 years with a broad range of clinical, neurocognitive, and functional outcomes assessments. MRI exams with multiple acquisition sequences will be conducted before treatment, after 16 weeks of controlled treatment, and after 3 years. Both established and innovative approaches to morphometric analysis will be used, enabling detailed mapping of neuroanatomic variations that are associated with group differences, longitudinal changes, and functional indices. The data obtained will have major implications for segregating initial from ongoing anatomic pathology, and specifying the relations of initial and ongoing pathologic processes to multidimensional response patterns and long-term outcomes.