Imaging Hippocampal Function in Psychosis

描述（由申请人提供）：我们拟研究早期精神病（ESOP）海马功能障碍的演变。海马体体积较小是精神分裂症患者大脑结构异常中最明显的特征之一。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，尚不清楚在疾病过程中海马结构和功能何时异常，以及海马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我们干预疾病过程的能力。我们将招募处于新发精神障碍早期的患者，利用高场7T磁共振成像研究海马结构，利用3T脑血容量（CBV）和BOLD信号磁共振成像研究海马活动。我们将在关系记忆测试中衡量表现，关系记忆是一种依赖海马体的记忆，在精神分裂症中受损。我们将对患者进行为期2年的随访，测量精神障碍患者海马体积的变化。我们预测，海马体活动在发病时就已经异常，并且在病程中不会发生显著变化。作为异常活动的结果，记忆功能在发病时就已经中度受损。在患病的头两年里，海马体活动的异常增加导致了海马体的结构变化。这种结构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体地图。首先，解剖图谱将区分整个海马前后区的四个扇形和两个区域的体积。利用这种高分辨率的海马体包裹，我们将检验前区CA1主要在精神病患者中受到影响的假设。其次，功能图将评估海马的四个部门和两个区域的CBV和BOLD信号。有了这些图谱，我们将检验精神病患者海马抑制减弱的假设。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，关系记忆是一种依赖海马体的记忆，在精神分裂症中受损。提出的纵向研究设计将使我们能够研究精神障碍海马功能障碍的时间。本研究项目的目标是鉴定用于精神疾病早期诊断的海马标记物。

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.