Longitudinal Imaging of Patients at Clinical Risk for Psychosis.

描述(由申请人提供)：重要的是要评估精神分裂症的早期阶段，以确定受影响的大脑部位，以便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)来识别大脑异常的区域，这将使我们了解精神分裂症早期进化和出现的机制。我们的团队发现了一种很有希望的成像生物标记物，它使用了一种高分辨率的功能磁共振成像变种，它使用Gd对比增强海马区的基本功能，它与精神分裂症本身有关，与妄想等疾病阶段的阳性精神症状的严重性有关，并在一小群人中预测从前驱症状或临床高危状态发展到精神病(Schobel，Lewandowski等人)。重要的是，到目前为止，这些发现是基于相对较少的受试者队列，27名精神分裂症患者，27名精神病临床高危患者，以及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，通过扩大精神分裂症和临床精神病风险患者的队列来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。这项建议的意义是明确测试使用高分辨率功能磁共振变体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功能磁共振变体检测精神分裂症早期阶段的效用，并澄清发病时脑功能异常与结构之间的关系。如果实现拟议的目标，我们对疾病前驱阶段的诊断能力将得到提高，我们对紧急精神疾病的病理生理学的了解也将得到加强，这两者都是制定预防性干预措施的关键，以努力降低精神分裂症和相关精神障碍的显著发病率。 与公共健康相关：精神分裂症和所有脑部疾病一样，比其他疾病更多地针对特定的大脑区域。通过脑成像精确定位这些靶区具有挑战性，但对于诊断目的和了解疾病机制来说，这一点很重要。在这项应用中，我们将使用两种不同的脑功能成像，它们可以检测大脑小区域的疾病相关功能障碍，并将其应用于临床上有精神病风险的患者，他们将接受前瞻性的临床和脑成像结果跟踪。该项目的主要目标是明确地测试海马体功能亢进是精神分裂症和相关疾病的致病驱动因素的假说。

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.