IN VIVO STUDIES OF THE PI PATHWAY IN BIPOLAR DISORDER

双相情感障碍 PI 通路的体内研究

• 批准号: 7627522
• 负责人: JAIR C SOARES
• 金额: $ 5.98万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7627522
• 关键词: Bipolar Disorder; Blood Platelets; Blood specimen; Brain; Brain scan; Computer Retrieval of Information on Scientific Projects Database; Condition; DSM-IV; Densitometry; Depressed mood; Development; Diagnosis; Diagnostic; Disease; Functional disorder; Funding; Grant; Inositol; Institution; Lasers; Lithium; Magnetic Resonance Spectroscopy; Manic; Measurement; Membrane; Pathway interactions; Patients; Phosphatidylinositols; Protons; Recruitment Activity; Research; Research Personnel; Resources; Scanning; Source; Thin Layer Chromatography; United States National Institutes of Health; clinically relevant; frontal lobe; in vivo; two-dimensional

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The phosphoinositol (PI) pathway may be abnormal in bipolar disorder, and this could be an important mechanism involved in its pathophysiology and the mechanisms of action of lithium and other treatments for this condition. This study will investigate in vivo the intracellular PI pathway in bipolar disorder patients, and examine the hypothesis of a dysfunction in this pathway in patients suffering from this disorder. RESEARCH PLAN: We will recruit 90 un-medicated bipolar subjects (30 depressed, 30 euthymic, 30 manic), 30 lithium-treated euthymic patients, and 60 matched healthy controls over the course of a 5 year period. Patients will be diagnosed according to the DSM-IV criteria and need to meet diagnostic criteria for bipolar disorder type I. METHODS: Patients will provide blood samples for determination of platelet membrane phosphoinositides, which will be done with two-dimensional thin-layer chromatography followed by scanning laser densitometry. They will also undergo a 1.5T proton magnetic resonance spectroscopy (MRS) brain scan, which will allow the quantitation of may-inositol in a single voxel placed in the frontal cortex. Correlations will be examined between brain myo-inositol and platelet phosphoinositide levels and between these measurements and specific disease states. The impact of lithium treatment will also be examined. CLINICAL RELEVANCE: This study may result in substantial contributions to the understanding of the pathophysiology of bipolar disorder and ultimately contribute to the development of new treatments for this condition.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：双相情感障碍患者的磷脂酰肌醇(PI)通路可能存在异常，这可能是其病理生理机制及锂等药物治疗的重要机制之一。这项研究将在体内研究双相情感障碍患者的细胞内PI途径，并检验患有这种障碍的患者这一途径功能障碍的假说。 研究计划：在5年的时间里，我们将招募90名未用药的双相情感受试者(30名抑郁症患者，30名欣快症患者，30名躁狂症患者)，30名接受锂盐治疗的患者，以及60名匹配的健康对照组。患者将根据DSM-IV标准进行诊断，并需要满足I型双相情感障碍的诊断标准。 方法：患者提供血样用于血小板膜磷脂的测定，用二维薄层层析和扫描激光密度计进行。他们还将接受1.5T质子磁共振波谱(MRS)脑扫描，这将允许定量放置在额叶皮质的单个体素中的肌醇。将检查脑肌醇和血小板磷脂酰肌醇水平之间的相关性，以及这些测量和特定疾病状态之间的相关性。锂治疗的影响也将被检查。 临床意义：这项研究可能会对了解双相情感障碍的病理生理学做出实质性贡献，并最终有助于开发这种疾病的新治疗方法。