HIPPOCAMPAL METABOLISM IN SCHIZOPHRENIA

精神分裂症的海马代谢

• 批准号: 3475525
• 负责人: THOMAS EDWARD NORDAHL
• 金额: $ 16.93万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3475525
• 关键词: antipsychotic agents; brain metabolism; corpus striatum; deoxyglucose; haloperidol; hippocampus; human subject; magnetic resonance imaging; positron emission tomography; schizophrenia

Recent data, obtained by magnetic resonance imaging (MRI), positron emission tomography (PET), electrophysiological methods, and post-mortem examination, suggest that there may be an abnormality in the anterior hippocampal region (including amygdala) in schizophrenia. Hippocampal involvement in schizophrenia is supported by findings indicating that lesions in or stimulation of the hippocampal region can cause symptoms typical of schizophrenia. There is evidence that antipsychotic agents, such as remoxipride and clozapine, may act upon the mesolimbic dopamine system and this lends support to the notion that a functional hippocampal defect in patients with schizophrenia may be a causative factor in the typical symptoms of schizophrenia. Also, myelination of cortico-hippocampal relays occurs during late adolescence, generally the earliest time of onset of psychotic symptoms in patients with schizophrenia. Prefrontal decrease in regional cerebral metabolic rate of glucose (rCMRglc) measured by PET has been noted in some studies of chronic, medication-free patients. This could be related to a defect in the hippocampal region. This project will use the high-resolution (2.6 mm) 600-crystal PET (PET-600) and the tracer [F-18]-2-fluoro-2-deoxyglucose (FDG) for the measurement of rCMRglc in schizophrenia. We will correlate rCMRglc in the hippocampal region with typical symptoms of schizophrenia, in order to test the hypothesis that the hippocampal function is involved in producing these symptoms. We will also study the effects of two different anti-psychotic agents, remoxipride and haloperidol, on hippocampal, limbic, and striatal glucose metabolism in schizophrenia. An important strength of the proposed research is the use of a PET system with sufficient spatial resolution to quantitate activity in the hippocampal region. Blurring (lower recovery coefficients) seen in lower resolution systems results in a reduction of the apparent metabolic rate. High resolution of the scanner, however, increases the need for accuracy of positioning. We achieve this accuracy by the use of high resolution emission and transmission images obtained with the same instrument, as well as with magnetic resonance imaging (MRI). A total of 24 normal subjects and 24 patients with schizophrenia will be studied over a 4 year period. Twelve of the patients will be studied after a two week medication-free period and again after six weeks of treatment with remoxipride. The remaining twelve patients will be studied after two weeks free of medication and again after six weeks of treatment with haloperidol. This project is focused on the investigation of hippocampal metabolism in schizophrenia seeking to localize functional abnormalities. The relationship between anterior hippocampal region (including amygdala) and striatal region rCMRglc with psychotic and motor symptoms of schizophrenia will be studied.

最新数据，通过磁共振成像（MRI）获得，正电子 排放断层扫描（PET），电生理方法和验尸后 检查，表明前部可能有异常 精神分裂症中的海马区（包括杏仁核）。 海马 研究结果表明，参与精神分裂症的参与表明 海马区域的病变或刺激可能引起症状 精神分裂症的典型特征。 有证据表明抗精神病药， 例如雷莫斯克里德和氯氮平，可能作用于中唇胺的多巴胺 系统及其对功能性海马的概念提供了支持 精神分裂症患者的缺陷可能是导致因素 精神分裂症的典型症状。 另外，髓鞘 皮质 - 海马继电器发生在青春期晚期，通常 患者的精神病症状发作最早的时间 精神分裂症。 区域大脑代谢率的前额叶降低 通过PET测量的葡萄糖（RCMRGLC）在某些研究中已注意到 慢性，无药物的患者。 这可能与缺陷有关 海马区。 该项目将使用高分辨率（2.6毫米）600晶体宠物 （PET-600）和示踪剂[F-18] -2-Fluoro-2-脱氧葡萄糖（FDG） 精神分裂症中RCMRGLC的测量。 我们将在 具有精神分裂症典型症状的海马区域，以测试 海马功能与生产有关的假设 症状。 我们还将研究两种不同的反精神病的影响 在海马，边缘和纹状体上的剂，雷莫西和氟哌啶醇 精神分裂症中的葡萄糖代谢。 拟议研究的重要优势是使用宠物系统 具有足够的空间分辨率来定量活性 海马区。 在较低的 分辨率系统导致明显的代谢率降低。 但是，扫描仪的高分辨率增加了对准确性的需求 定位。 我们通过使用高分辨率实现了这种准确性 发射和传输图像也用相同的仪器获得 与磁共振成像（MRI）一样。 共有24名正常受试者和24例精神分裂症患者将是 在4年内学习。 十二例患者将在 一个两周的无药物治疗后，又有六周的治疗 与Remoxipride。 两名患者将在两次之后进行研究 几周没有药物治疗，经过六周的治疗 氟哌啶醇。 该项目的重点是调查海马代谢 试图定位功能异常的精神分裂症。 这 前海马区（包括杏仁核）和 具有精神分裂症的精神病和运动症状的纹状体区域RCMRGLC 将被研究。