Longitudinal Imaging of Patients at Clinical Risk for Psychosis.

摘要 重要的是在早期阶段评估精神分裂症，以确定大脑部位， 受影响，以便更好地了解疾病的原因， 制定干预措施。一个主要的研究目标是利用磁共振成像 (MRI)以确定大脑异常的区域，这将告知我们的知识， 精神分裂症早期演变和出现的潜在机制。我们的团队发现 一种有前途的成像生物标志物，使用钆功能MRI的高分辨率变体 对比-海马亚区的基础功能增加，这与 精神分裂症本身，与各疾病阶段阳性精神病症状的严重程度有关 例如妄想，以及从前驱症状或临床高风险发展为精神病的预测。 在一个小队列中的状态（Schobel，Lewandowski等人，2009） 重要的是，迄今为止的这些发现是基于相对较小的受试者队列，27 精神分裂症患者，27例精神病临床高风险患者，24例 比较科目。我们的目标是在我们以前发表的研究的基础上， 精神分裂症和精神病临床风险患者的队列，以测试 推定标记物，并包括脑功能和结构的纵向评估。的 这项建议的意义在于明确测试使用高分辨率功能磁共振成像变体的效用 检测精神分裂症的最早阶段，测试使用低分辨率非- 侵入性fMRI变异检测精神分裂症的最早阶段，并阐明 异常的大脑功能和结构之间的联系如果拟议的目标得以实现， 我们在疾病前驱阶段的诊断能力将得到加强， 了解紧急精神病的病理生理学，这两者都是关键， 制定预防性干预措施，努力减少 精神分裂症和相关精神障碍。

Abstract It is important to evaluate schizophrenia in its early stages in order to identify brain sites that are affected, such that causes of illness may be better understood and appropriate preventive interventions developed. A major research goal has been to use magnetic resonance imaging (MRI) to identify areas of brain abnormality which would inform our knowledge as to the mechanisms underlying the early evolution and emergence of schizophrenia. Our group identified a promising imaging biomarker using a high-resolution variant of functional MRI using gadolinium contrast- increased basal function in hippocampal subregions, which was associated with schizophrenia itself, related to the severity of positive psychotic symptoms across illness stages such as delusions, and predicted progression to psychosis from a prodromal or clinical high-risk state in a small cohort (Schobel, Lewandowski et al. 2009) Importantly, these findings to date are based upon a relatively small cohort of subjects, 27 patients with schizophrenia, 27 patients who are at high clinical risk for psychosis, and 24 comparison subjects. We aim to build upon our previous published study by expanding the cohort of schizophrenia and patients at clinical risk for psychosis to test the predictive value of the putative marker, and include longitudinal assessment of brain function and structure. The significance of this proposal is to definitively test the utility of using a high-resolution fMRI variant to detect the earliest stages of schizophrenia, to test the utility of using a lower-resolution non- invasive fMRI variant to detect the earliest stages of schizophrenia, and to clarify the relationship between abnormal brain function and structure in its onset. If the proposed aims are achieved, our diagnostic capabilities in prodromal stages of disease will be enhanced as well as our understanding of the pathophysiology of emergent psychotic illness, both of which are key to developing preventative interventions in an effort to reduce the significant morbidity of schizophrenia and related psychotic disorders.