Imaging Hippocampal Function in Psychosis

描述(由申请人提供)：我们建议研究精神病早期(ESOP)海马区功能障碍的演变。在精神分裂症患者中，海马体体积变小是最强烈的结构性脑异常之一。此外，现在有令人信服的证据表明精神分裂症患者的海马体活动异常。然而，目前尚不清楚在疾病过程中，海马体结构和功能何时变得异常，以及海马体的哪些区域受到影响。澄清这些问题将提高我们对疾病机制的理解和干预疾病过程的能力。我们将招募新出现的精神病患者的早期阶段，用高场7T磁共振成像研究海马结构，用3T磁共振脑血容量图(CBV)和BOLD信号研究海马活动。我们将测量在关系记忆测试中的表现，关系记忆是精神分裂症中受损的一种海马体依赖记忆。我们将对患者进行为期2年的跟踪，并测量精神障碍患者的海马体体积的变化。我们预测，海马体活动在疾病开始时就已经异常，并且在疾病过程中不会有明显的变化。作为异常活动的结果，记忆功能在发病时已经中度受损。在疾病的头两年中，海马体活动的异常增加导致海马体结构的变化。这种结构性变化与记忆缺陷的进一步发展有关。为了验证我们的假设，我们将开发两种类型的高分辨率海马区地图。首先，解剖图将区分整个海马体前后部的四个扇区和两个区域的体积。利用这张高分辨率的海马区切片，我们将检验这一假设，即精神障碍患者的前部CA1主要受影响。其次，功能图将评估海马体四个扇区和两个区域的CBV和BOLD信号。利用这些图谱，我们将检验精神病患者海马区抑制减弱的假说。我们将把海马体结构和活动的测量与关系记忆测试的表现联系起来，关系记忆是精神分裂症中受损的一种海马体依赖记忆。拟议的纵向研究设计将使我们能够研究精神障碍患者海马区功能障碍的时间。本研究项目的目标是确定用于精神障碍早期诊断的海马区标志物。

DESCRIPTION (provided by applicant): We propose to study the evolution of hippocampal dysfunction in the early stage of psychosis (ESOP). Smaller hippocampal volume is one of the most robust structural brain abnormalities in patients with schizophrenia. In addition, there is now compelling evidence for an abnormality of hippocampal activity in schizophrenia. However, it is unclear when in the disease process hippocampal structure and function become abnormal and which regions of the hippocampus are affected. Clarifying these questions will improve our understanding of the disease mechanism and our ability to intervene in the disease process. We will recruit patients at an early stage of their emerging psychotic disorder to study hippocampal structure with high-field 7T magnetic resonance imaging and hippocampal activity with 3T magnetic resonance mapping of cerebral blood volume (CBV) and BOLD signal. We will measure performance on tests of relational memory, a form of hippocampus-dependent memory that is impaired in schizophrenia. We will follow patients for 2 years and measure the change of hippocampal volume in psychotic disorders. We predict that hippocampal activity is abnormal already at the onset of the illness and does not change significantly over the course of the illness. As a consequence of abnormal activity, memory function is already moderately impaired at illness onset. Over the course of the first 2 years of illness, the abnormally increase activity of the hippocampus leads to structural changes in the hippocampus. This structural change is associated with a further progression of memory deficits. To test our hypotheses, we will develop two types of high-resolution hippocampal maps. First, anatomical maps will distinguish the volume of four sectors and two regions throughout the entire anterior-posterior extent of the hippocampus. Using this high-resolution parcellation of the hippocampus, we will test the hypothesis that the anterior sector CA1 is primarily affected in psychotic disorder patients. Second, functional maps will assess CBV and BOLD signal in the four sectors and two regions of the hippocampus. With these maps we will test the hypothesis of decreased hippocampal inhibition in psychotic disorders. We will correlate the measures of hippocampal structure and activity with the performance on tests of relational memory, a form of hippocampus- dependent memory that is impaired in schizophrenia. The proposed longitudinal study design will allow us to study the timing of hippocampal dysfunction in psychotic disorders. The goal of this research project is the identification of hippocampal markers for the early diagnosis of psychotic disorders.