IN VIVO STUDIES OF THE PI PATHWAY IN BIPOLAR DISORDER

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 目的：磷酸肌醇（PI）通路在双相情感障碍中可能异常，这可能是其病理生理学和锂和其他治疗方法作用机制的重要机制。 本研究将在体内研究双相情感障碍患者的细胞内PI通路，并检查患有这种疾病的患者在此通路中的功能障碍的假设。 研究报告：我们将招募90名未经药物治疗的双相情感障碍受试者（30名抑郁症患者，30名正常心境患者，30名躁狂症患者），30名锂治疗的正常心境患者和60名匹配的健康对照，为期5年。 患者将根据DSM-IV标准进行诊断，并且需要符合I型双相情感障碍的诊断标准。 方法：患者将提供用于测定血小板膜磷酸肌醇的血液样本，这将通过二维薄层色谱法随后扫描激光密度测定法完成。 他们还将接受1.5T质子磁共振波谱（MRS）脑部扫描，这将允许在额叶皮层中放置的单个体素中定量五月肌醇。 将检查脑肌醇和血小板磷酸肌醇水平之间的相关性，以及这些测量结果与特定疾病状态之间的相关性。 还将研究锂处理的影响。 临床相关性：这项研究可能会对双相情感障碍的病理生理学的理解做出重大贡献，并最终有助于开发这种疾病的新治疗方法。

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.