NEUROPSYCHOLOGICAL AND NEUROIMAGING ABNORMALITIES IN SIBLING PAIRS DISCORDANT

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心，不一定是研究者所在机构。目的：本研究的目的是确定在BPD患者中发现的神经心理学和结构MRI异常是否存在于其未受影响的兄弟姐妹中，从而提高这些措施可用作BPD内表型的可能性。 研究方法：1. 对20对BPD不一致的兄弟姐妹（20名BPD患者和20名他们的兄弟姐妹）和20名匹配的健康受试者进行神经心理学的注意力、执行功能、工作记忆和陈述记忆测试。我们假设这些措施将在BPD患者受损，并在较小程度上，他们的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采集高质量的结构MRI图像，以更好地定义与BPD相关的前额和内侧颞叶/边缘异常。我们假设前额叶皮质异常对BPD的遗传易感性敏感，并将探讨杏仁核异常与BPD风险相关的可能性。 精神相关性：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，尽管有大量证据表明BPD的风险是遗传的，但这种疾病的分子遗传基础仍然难以捉摸。鉴于有证据表明，诱发BPD的基因可能在没有临床表型表达的情况下传播，人们对开发基因型和表型之间介导过程的指标产生了兴趣。此类同源表型或内表型可直接指示潜在病理或疾病易感性，因此可在受影响和未受影响的个体中测量。这些标记物通常是定量的，这将允许尚未用于定性表型标记物的分析策略。开发BPD的内表型标记的最终希望是促进与疾病相关的遗传位点的搜索，并在基因型携带者中隔离环境对疾病表达的贡献，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 healthy 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 associated 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. CLINCAL 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 phonotype. 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 endophenotypic 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.