BRAIN MYELIN INTEGRITY IN BIPOLAR DISORDER: AN IN VIVO MAGNETIC RESONANCE IMG

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：直到最近，脑髓鞘和白质还不是双相情感障碍患者的主要研究重点。髓鞘(隔离神经的白质)和影响髓鞘形成的因素都是可以深刻影响神经元连接的过程。解剖磁共振成像(MRI)研究表明，双相情感障碍患者脑白质高信号的比率增加，这可能破坏了与这种疾病的病理生理有关的大脑结构之间的连接。最近，有报道显示双相情感障碍患者的胼胝体(一种连接两个大脑半球的白质中线结构，允许两个半球之间的交流)的特定亚区体积较小，MRI信号强度降低。这些发现提示髓鞘和白质异常参与了双相情感障碍的病理生理学。本研究旨在探讨双相情感障碍患者脑白质区域是否存在局部髓鞘异常。 研究计划：我们建议利用一种新的方法来测量髓鞘的完整性，该方法基于三池的概念，该概念提出髓鞘将水部分分离为髓鞘、有髓轴突和混合池。在我们的初步研究中，三池方法成功地估计了髓鞘形成的速度和开始。我们将使用1.9特斯拉磁共振磁铁对30名未经治疗的双相情感障碍患者和30名匹配的健康对照进行研究。 方法：我们将招募30名未经治疗的双相情感障碍患者和30名年龄、性别和种族相匹配的健康对照，总共60人，在两年的时间里，男性和女性，年龄18-75岁。双相情感障碍患者的纳入标准是：a)DSM-IV诊断为I型双相情感障碍；b)过去6个月内没有药物滥用；c)没有目前的医疗问题；d)在参与研究时至少两周没有接受精神药物治疗；以及e)除焦虑障碍外，没有共病的精神障碍。精神病学诊断将根据DSM-IV标准，使用SCID-IV面谈建立，并随后在研究精神病学家的临床评估中得到确认。汉密尔顿抑郁量表-17项和青年躁狂评定量表将用于评估临床症状的严重程度。标准的神经心理组合将在进入方案时进行管理，以调查神经心理缺陷的可能性。所有受试者都将接受脑部核磁共振扫描，扫描过程一次进行，耗时2小时。所有图像将在大口径1.9T磁共振成像系统(Elscint，Haifa，以色列)上获取。统计分析将使用SPSS版本11.5软件(SPSS，Inc.，芝加哥，伊利诺伊州)进行。 临床意义：这项研究将首次调查双相情感障碍患者的大脑髓鞘完整性，并通过这样做，有助于了解相关的疾病机制。它最终可能导致开发出针对这种疾病的新的、更有效的治疗干预措施。

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: Until recently, brain myelin and white matter have not been a major focus of investigation in bipolar patients. Myelin (the white matter insulating the nerves), and factors that affect myelination are processes that could profoundly affect neuronal connectivity. Anatomical magnetic resonance imaging (MRI) studies have shown increased rates of white matter hyperintensifies in bipolar disorder, which might be disrupting connectivity among the brain structures implicated in the pathophysiology of this disorder. Recently, reports indicating smaller size and decreased MRI signal intensity in specific sub-regions of corpus callosum (a white matter midline structure that connects the two brain hemispheres, allowing inter-hemispheric communication) in bipolar patients have appeared. These findings suggest the involvement of myelin and white matter abnormalities in the pathophysiology of bipolar disorder. The purpose of this study is to examine whether there are regional myelin abnormalities in white matter brain regions in bipolar patients. RESEARCH PLAN: We propose to utilize a new method to measure myelin integrity, based on the three-pool concept, which proposes that myelin segregates water fractions into myelin, myelinated axons, and mixed pools. The three-pool method successfully estimated the rate and onset of myelination in our preliminary studies. We will study a group of 30 untreated bipolar patients and 30 matched healthy controls, using a 1.9 Tesla MRI magnet. METHODS: We will recruit a group of 30 untreated bipolar patients and 30 healthy controls matched for age, gender and ethnicity, for a total of 60 persons, over a 2-year period, both male and female, ages 18-75. Inclusion criteria for bipolar patients are: a) DSM-IV diagnosis of bipolar disorder type I; b) no substance abuse within the past 6 months; c) no current medical problems; d) not receiving psychotropic medications for at least two weeks at the time of participation in the study; and e) no comorbid psychiatric disorders, except for Anxiety Disorders. Psychiatric diagnosis will be established according to the DSM-IV criteria, using the SCID-IV Interview, and confirmed subsequently in a clinical evaluation by a research psychiatrist. The Hamilton Depression Rating Scale - 17 items and the Young Mania Rating Scale will be used to rate the severity of clinical symptoms. A standard neuropsychological battery will be administered at the time of entrance in the protocol to investigate the possibility of neuropsychological deficits. All subjects will undergo a brain MRI scan, which is performed in a single session and takes 2 hours. All images will be acquired on a large-bore 1.9 T MRI system (Elscint, Haifa, Israel). Statistical analyses will be performed using SPSS version 11.5 software (SPSS, Inc., Chicago, IL). CLINICAL RELEVANCE: This study will investigate, for the first time, brain myelin integrity in bipolar disorder, and by doing so, contribute to understanding the disease mechanisms involved. It could ultimately result in the development of new and more effective therapeutic interventions for this disorder.