NEUROPSYCHOLOGICAL AND NEUROIMAGING ABNORMALITIES IN SIBLING PAIRS DISCORDANT

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：本研究的目的是确定在BPD患者中发现的神经心理和结构MRI异常是否存在于他们未受影响的同胞中，从而提高这些指标可用于BPD的内表型的可能性。 研究计划和方法： 1.对20对不符合BPD的兄弟姐妹(20名BPD患者及其20名兄弟姐妹)和20名匹配的高热受试者进行注意力、执行功能以及工作和陈述性记忆的神经心理学测试。我们推测，这些措施在BPD患者中会受到损害，在较小程度上也会损害他们未受影响的兄弟姐妹。 2.使用Siemens 3 Telsa MRI扫描仪，在同一样本中获得高质量的结构MRI图像，以更好地确定与BPD相关的前额叶和内侧颞缘异常。我们假设前额叶皮质的异常对BPD的遗传易感性很敏感，并将探索杏仁核异常与BPD风险相关的可能性。 临床意义：双胞胎家庭和收养研究表明，双相情感障碍(BPD)基本上是可遗传的。然而，尽管有相当多的证据表明BPD的风险是遗传的，但这种疾病的分子遗传学基础仍然难以捉摸。鉴于有证据表明BPD的易感基因可能在没有临床表型表达的情况下传播，人们对开发在基因和表型之间调节过程的指示剂产生了兴趣。这种相关的表型或内表型可以直接指示潜在的病理或疾病易感性，因此可以在受影响和未受影响的个体中进行测量。这些标记通常是定量的，这将允许采取定性表型标记所不具备的分析策略。为BPD开发内生型标记的最终希望是促进与该疾病相关的遗传位点的搜索，以及分离环境对基因携带者疾病表达的影响，可能导致预防或治疗策略。

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 aim of this study is to determine if neuropsychological and structural MRI abnormalities identified in BPD patients are present in their unaffected siblings, raising the potential that these measures could be used as endophenotypes for BPD. RESEARCH PLAN AND METHODS: 1. Apply a neuropsychological battery of tests of attention, executive function, and working and declarative memory to 20 sibling pairs discordant for BPD (20 BPD patients and 20 of their siblings) and 20 matched heatlhy subjects. We hypothesize that these measures will be impaired in BPD patients, and to a lesser degree, to their unaffected siblings. 2. Acquire high quality Structural MRI images, using a Siemens 3 Telsa MRI scanner, in this same sample to better define the prefrontal and medial temporal/limbic abnormalities aasociated with BPD. We hypothesize that abnormalities in the prefrontal cortex will be sensitive to genetic liability for BPD and will explore the possibility that amygdale anomalies are associated with risk for BPD. CLINICAL RELEVANCE: Twin family and adoption studies have demonstrated that bipolar disorder (BPD) is substantially heritable. Yet, despite considerable evidence that risk for BPD is inherited, the molecular genetic basis for this illness remains elusive. Given evidence that genes predisposing to BPD may be transmitted without expression of the clinical phenotype, interest has arisen in developing indicators of processes mediating between genotype and phenotype. Such allied phenotypes, or endophenotypes, may directly index the underlying pathology, or liability to disease, and hence can be measured in both affected and unaffected individuals. These markers are often quantitative, which will allow for analysis strategies that have not been available for qualitative phenotypic markers. The ultimate promise of developing endophynotypic markers for BPD is to facilitate the search for genetic loci associated with the disorder and in the isolation of environmental contributions to illness expression among genotype carriers, possibly leading to prevention or treatment strategies.