GENETICS OF BIPOLAR DISORDER IN LATINO POPULATIONS

拉丁裔人群双向情感障碍的遗传学

• 批准号: 7718754
• 负责人: Michael A Escamilla
• 金额: $ 0.04万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718754
• 关键词: Affect; Amygdaloid structure; Anterior; Atlases; Bipolar Disorder; Brain; Brain region; Cerebral aqueduct; Cerebrospinal Fluid; Computer Retrieval of Information on Scientific Projects Database; DNA; DSM-IV; Data; Diagnosis; Diagnostic; Family; Family member; Funding; Generations; Genes; Genetic; Goals; Grant; Gray unit of radiation dose; Hispanics; Image; Individual; Institution; Latino; Left; Magnetic Resonance; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Neurocognitive; Patients; Population; Positioning Attribute; Predisposition; Procedures; Protons; Publishing; Range; Relative (related person); Reporting; Research; Research Personnel; Resources; Sample Size; Sampling; Scanning; Series; Siblings; Site; Slice; Source; Standards of Weights and Measures; Structure; Testing; Thick; Three-Dimensional Image; Three-Dimensional Imaging; Time; Training; United States National Institutes of Health; Weight; base; case control; density; endophenotype; experience; genetic pedigree; gray matter; interest; size; trait; white matter

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. 2007 OBJECTIVE: The goal of this project is to collect diagnostic information and DNA samples from 385 families of Latino descent, each with a minimum of two siblings affected with BPI (DSM-IV diagnosis) in order to detect BPI susceptibility loci in this population. Endophenotypes defined by neurocognitive and structural MRI tests related to BPI will be validated in these pedigrees and genes which contribute to these biologic variables will also be mapped through covariate quantitative trait analyses. RESEARCH PLAN AND METHODS: Imaging data will be acquired for a subset of subjects (from approximately 30 families) at the San Antonio site in order to validate structural imaging measures as endophenotypes. We will obtain MRIs for approximately 60 subjects a year (15 siblings with BPI, 30 unaffected siblings, and 15 controls) over a four year period. We have extensive experience in obtaining these MRIs for BP subjects and controls and have done so for 140 subjects over the last two years. We will use a GE/Elscint Prestige 2-T high-field magnetic resonance (MR) scanner, located at the UTHSCSA Research Imaging Center (RIC). The scans will be performed by a highly trained MR technician. A sagittal scout series is first obtained to verify patient position, image quality, and clarity of the full extent of the aqueduct of sylvius to locate a midline sagittal image. 3D T1-FFE (T-1 weighted fast field echo) will be performed in the coronal plane with TR of 25 ms, TE of 5 ms, flip angle of 40o, field of view (FOV) 240 mm x 220 mm, slice thickness of 1.0 mm, NEX=2 and matrix size of 256x192, to obtain images covering the entire brain. We will additionally use a spin echo sequence to obtain T2 and proton density images in the axial plane and screen for neuroradiological abnormalities. The total time to collect the 3D T1-FFE and spin echo sequence is approximately 25 minutes. The proposed regions-of-interest (ROIs) will be identified and delineated according to previously published methods for anatomical MRI measurements of these particular brain regions. The anatomical regions will be identified in 3 anatomical planes, in reference to standard anatomical brain atlases, and examination of the three-dimensional volume-rendered view of these structures will be used to facilitate identification of boundaries. All morphometric measures will be performed by raters well trained to do these specific procedures, and who have achieved inter-rater reliability of over 0.90 for these specific measurements. The volume of gray and white matter and cerebrospinal fluid (CSF) in the brain ROIs will be estimated using the 3D T1-FFE MRI data and a semi-automated segmentation method based on the generation of histogram of gray, white matter and cerebrospinal fluid pixel intensities. This method uses a histogram approach to determine the thresholds for separation of gray matter, white matter, and CSF, as per method previously described 180,181,186,187. With the proposed sample size of 60 affected individuals and 60 healthy comparison subjects, we will have 80% power (1-b%) to reject the null hypothesis (a=0.05) of no between group difference for a contrast with small effect size (minimum effect size = 0.25). Given the effect sizes of case-control contrast for the anterior cingulate (effect size=1.08) and left amygdala (effect size=0.64) reported above, we anticipate power to detect between group differences to vary from 96 to 99.9%. Assuming that volumetric measurements for unaffected relatives are midway between affected and unrelated individuals, with 120 unaffected family members and 60 healthy comparison subjects, we anticipate power to detect between group differences to range from 59 to 99.6%, depending on the ROI.

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。 2007年 目的：本项目的目的是收集385个拉丁裔家庭的诊断信息和DNA样本，每个家庭至少有两个兄弟姐妹患有BPI(DSM-IV诊断)，以检测该人群中BPI的易感基因。与BPI相关的神经认知和结构MRI测试所定义的内表型将在这些家系中得到验证，影响这些生物变量的基因也将通过协变量数量性状分析进行定位。 研究计划和方法：将在圣安东尼奥遗址获取部分受试者(来自大约30个家庭)的成像数据，以验证结构成像测量作为内表型的有效性。我们将在四年内每年获得大约60名受试者的磁共振成像(15名患有BPI的兄弟姐妹，30名未受影响的兄弟姐妹，15名对照)。我们在为BP受试者和对照获得这些核磁共振成像方面拥有丰富的经验，在过去两年中已经为140名受试者这样做了。我们将使用位于UTHSCSA研究成像中心(RIC)的GE/Elscint Prestige 2-T高场磁共振(MR)扫描仪。扫描将由训练有素的MR技术人员执行。首先获得矢状面侦察序列，以验证患者的位置、图像质量和Sylvius导水管全范围的清晰度，以定位中线矢状面图像。3D T1-FFE(T-1加权快速场回波)在冠状面进行，TR25ms，TE 5ms，翻转角40o，视野240 mm×220 mm，层厚1.0 mm，NEX=2，矩阵大小256x192，获得覆盖全脑的图像。此外，我们还将使用自旋回波序列获得轴面上的T2和质子密度图像，并筛查神经放射异常。收集3D T1-FFE和自旋回波序列的总时间约为25分钟。 建议的感兴趣区(ROI)将根据先前发表的解剖MRI测量这些特定脑区的方法进行识别和描绘。解剖区域将参照标准解剖脑图谱在3个解剖平面上识别，并将检查这些结构的三维体积再现视图，以便于识别边界。所有的形态测量将由训练有素的评分员执行这些特定的程序，并且对于这些特定的测量，评分员之间的可信度超过0.90。使用3DT1-FFE MRI数据和基于灰质、白质和脑脊液像素强度直方图的半自动分割方法，估计脑ROI中灰质、白质和脑脊液(CSF)的体积。该方法使用直方图方法来确定灰质、白质和脑脊液分离的阈值，如前面描述的方法180、181、186、187。 在60个患病个体和60个健康对照受试者的拟议样本量下，我们将有80%的权力(1-b%)拒绝组间差异的零假设(a=0.05)，以进行小效应大小(最小效应大小=0.25)的对照。考虑到前面报道的病例对照对比对前扣带回(效应大小=1.08)和左侧杏仁核(效应大小=0.64)的效应大小，我们预计检测组间差异的能力从96%到99.9%不等。假设未受影响的亲属的体积测量介于受影响和无血缘关系的个体之间，有120名未受影响的家庭成员和60名健康对照受试者，我们预计检测组间差异的能力从59%到99.6%，取决于ROI。