IDENTIFICATION OF BIOMARKERS FOR LITHIUM SENSITIVITY IN BIPOLAR DISORDERS

双相情感障碍中锂敏感性生物标志物的鉴定

• 批准号: 8173614
• 负责人: CHIAKI FUKUHARA
• 金额: $ 12.9万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173614
• 关键词: Adult; Affect; Animals; Be++ element; Beryllium; Biological Assay; Biological Markers; Bipolar Disorder; Cell model; Cells; Clinical; Computer Retrieval of Information on Scientific Projects Database; Core Facility; Diagnostic; Disease; Family history of; Funding; Gene Expression; Gene Expression Profiling; Gene Mutation; Genes; Genetic; Goals; Grant; Human; Institution; Lithium; Manic; Medical center; Mental Depression; Mental disorders; Mood stabilizers; Patients; Pattern; Perception; Peripheral; Pharmaceutical Preparations; Recurrence; Reporting; Research; Research Personnel; Resources; Rest; Rodent; Sampling; Skin; Sleep Wake Cycle; Source; Suicide; Testing; Therapeutic; Therapeutic Effect; Tissue-Specific Gene Expression; United States; United States National Institutes of Health; brain cell; cost; functional genomics; prevent; response; trend

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. Bipolar disorder is characterized by recurrent episodes of mania and depression, a common psychiatric disorder. This disorder affects about 2.3 million adults every year in the US, costing $44 billion annually, but less than half of these patients are treated successfully. The mood stabilizer, lithium, has proven its efficacy in preventing the recurrence of mania and suicide more than any other drug for more than 50 years. In the past decade, however, lithium use in the United States has declined substantially, a trend not seen in the rest of the world. One of the reasons for this is the perception that lithium is more difficult to use. Additionally, only a subpopulation of patients shows benefits from lithium treatment, and therapeutic effects may not be fully apparent for several months. Therefore, it would be beneficial if there were a simple, rapid, and reliable assay that can be applied prior to treating patients with the drug to predict which patients will show a therapeutic response to lithium. Bipolar disorder patients with a family history of the disorder respond to lithium treatment better than those without such a family history, suggesting that lithium sensitivity is controlled in part by genetic factors. Since gene mutations affect not only the cells of the brain but also peripheral cells, lithium sensitivity may be predicted using peripheral cells. In the past, numerous studies have been conducted on gene expression by lithium stimulation in rodents and humans. The observation that lithium affects gene expression patterns in a variety of cells suggests that monitoring gene expression in human peripheral cells may provide a comprehensive diagnostic for patients' responsiveness to lithium. However, due to the lack of any animal or cell model regarding lithium sensitivity, no study exists in which differential gene expression is reported between lithium responders and nonresponders. Therefore, the goal of our present proposal is to identify a set of marker genes that are differentially expressed between lithium : responders and non-responders, and test our hypothesis that clinical response to lithium can be predicted using gene expression patterns in human peripheral cells. In addition to the P.I., the proposed study will be conducted by a team, which consists of the Functional Genomics Core Facility at MSM, and Dr. Ghaemi, Tufts Medical Center, MA. The proposed study will be an element within our bipolar disorder sleep-wake cycle study, in which we already have access to skin samples of bipolar patients.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 躁郁症的特征是躁狂和抑郁症的复发发作，这是一种常见的精神疾病。在美国，这种疾病每年影响约230万成年人，每年耗资440亿美元，但不到一半的患者被成功治疗。情绪稳定液锂已证明了其在50多年来比任何其他药物都比任何其他药物都多于预防躁狂和自杀的功效。然而，在过去的十年中，美国的锂使用大幅下降，这在世界其他地区未见。造成这种情况的原因之一是，人们认为锂更难使用。此外，只有患者的亚群显示出锂治疗中的好处，并且几个月内的治疗作用可能尚不完全显而易见。因此，如果有一个简单，快速和可靠的测定方法，可以在治疗药物患者之前预测哪些患者对锂的治疗反应，这将是有益的。具有该疾病家族史的双相情感障碍患者对锂治疗的反应比没有这样家族史的患者更好，这表明锂敏感性部分受遗传因素控制。由于基因突变不仅影响大脑的细胞，而且影响周围细胞，因此可以使用外围细胞预测锂敏感性。过去，啮齿动物和人类中锂刺激对基因表达进行了许多研究。锂会影响各种细胞中基因表达模式的观察结果表明，监测人外围细胞中的基因表达可能为患者对锂的反应提供全面的诊断。但是，由于缺乏有关锂敏感性的任何动物或细胞模型，尚无研究，其中锂反应者和无反应者之间均报道了差异基因表达。因此，我们目前的提议的目的是确定一组锂之间差异表达的标记基因： 响应者和无反应者，并检验我们的假设，即可以使用人外围细胞中的基因表达模式来预测对锂的临床反应。除P.I.外，拟议的研究还将由一个团队进行，该团队由MSM的功能基因组核心设施和马萨诸塞州塔夫茨医疗中心的Ghaemi博士组成。拟议的研究将是我们双相情感障碍睡眠效果周期研究中的一个元素，在该研究中，我们已经可以使用双极患者的皮肤样本。