Longitudinal Imaging of Patients at Clinical Risk for Psychosis.

描述（由申请人提供）：重要的是在早期阶段评估精神分裂症，以确定受影响的大脑部位，从而更好地了解疾病的原因并制定适当的预防干预措施。一个主要的研究目标是使用磁共振成像（MRI）来识别大脑异常区域，这将告知我们关于精神分裂症早期进化和出现的机制的知识。我们的研究小组通过使用钆对比的高分辨率功能性MRI变体确定了一种有前景的成像生物标志物——海马亚区基础功能增加，这与精神分裂症本身有关，与疾病阶段（如妄想）阳性精神病症状的严重程度有关，并在一个小队列中预测了从前驱或临床高危状态到精神病的进展（Schobel， Lewandowski等，2009）。到目前为止，这些发现是基于相对较小的受试者队列，27名精神分裂症患者，27名精神病临床高风险患者和24名对照受试者。我们的目标是在我们之前发表的研究的基础上，扩大精神分裂症和有精神病临床风险的患者的队列，以测试假定标记物的预测价值，并包括对大脑功能和结构的纵向评估。这项提议的意义在于明确测试使用高分辨率fMRI变体来检测精神分裂症早期阶段的效用，测试使用低分辨率非侵入性fMRI变体来检测精神分裂症早期阶段的效用，并阐明异常脑功能与发病结构之间的关系。如果提出的目标得以实现，我们在疾病前驱阶段的诊断能力将得到提高，同时我们对突发精神疾病的病理生理学的理解也将得到加强，这两者都是开发预防性干预措施以减少精神分裂症和相关精神疾病显著发病率的关键。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Schizophrenia, like all diseases of the brain, targets specific brain regions more than others. Pinpointing these targeted regions with brain imaging is challenging but important, for diagnostic purposes and for understanding mechanisms of disease. In this application we will use two variants of functional brain imaging that can detect disease-associated dysfunction in small regions of the brain and apply this to patients at clinical risk for psychosis who are followed prospectively for clinical and brain imaging outcomes. The main project goal is to definitively test the hypothesis of hippocampal hyperfunction as a pathogenic driver in schizophrenia and related disorders.