Developing Blood Tests for Mood Disorders

开发情绪障碍的血液测试

• 批准号: 7981594
• 负责人: Alexander B Niculescu
• 金额: $ 231万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7981594
• 关键词: Animal Model; Area; Biological Markers; Bipolar Disorder; Blood; Blood Tests; Brain; Caring; Clinical; Complex; Development; Disease; Future; Gene Expression; Genes; Genetic; Health; Health Care Costs; Hospitalization; Interview; Laboratories; Manic; Medical; Mental Depression; Modality; Mood Disorders; Moods; Nature; Patient Self-Report; Patients; Personal Satisfaction; Pharmaceutical Preparations; Pilot Projects; Probability; Quality of life; Reliance; Sensitivity and Specificity; Series; Symptoms; Testing; Work; base; cohort; economic impact; high reward; high risk; human subject; impression; improved; social

DESCRIPTION (Provided by the applicant) Abstract: There are to date no clinical laboratory blood tests for mood disorders. Given the complex nature of mood disorders, the current reliance on patient self-report of symptoms and the clinician's impression on interview of patient is a rate limiting step in delivering the best possible care with existing treatment modalities, as well as in developing new and improved treatment approaches, including new medications. We have provided proof of principle for an approach to help identify blood biomarkers for mood disorders (Le-Niculescu et al. 2009). Such biomarkers can serve as a basis for objective clinical laboratory tests. Our approach to identifying candidate biomarkers is based on the integration of genetic and gene expression studies, in human subjects and animal models. In pilot studies in this area, recently published1 (Le- Niculescu et al. 2009) we have identified a series of high probability blood candidate biomarker genes for mood state that deserve future scrutiny. A predictive score developed based on a panel of ten top candidate biomarkers (five for high mood, five for low mood) shows sensitivity and specificity for high mood (mania) and low mood (depression) states, in two independent patient cohorts. Our preliminary studies suggest that blood biomarkers may offer an unexpectedly informative window into brain functioning and disease state. This high-risk, high reward work needs to be extended and refined, which is what we propose to do. The development of clinical laboratory blood tests for mood disorders such as depression and bipolar disorder will have an impact on patient health, well-being, quality of life, and independent functioning, as well as decrease hospitalizations and overall health-care costs. Given the fact that 1 in 5 people in the US will suffer from a major mood disorder in their lifetime, the potential medical, social and economic impact of such work cannot be overstated. Public Health Relevance: No objective clinical laboratory tests for psychiatric disorders exist to date. The current reliance on imprecise diagnostic classifications, on the patient's self-report of symptoms and the clinicians impression, leads to less than optimal diagnosis and treatment of these prevalent, distressing and disabling conditions. Moreover, the lack of objective diagnostic tests constitutes a significant barrier to the development of new medications and treatment approaches. Our work aims to provide solutions to these problems.

描述(由申请人提供) 摘要：到目前为止，还没有针对情绪障碍的临床实验室血液测试。鉴于情绪障碍的复杂性质，目前依赖于患者对症状的自我报告和临床医生对患者面谈的印象是利用现有治疗方式提供尽可能好的护理以及开发包括新药在内的新的和改进的治疗方法的速度限制步骤。我们已经为帮助识别情绪障碍的血液生物标记物的方法提供了原则证据(Le-Nulescu等人。2009年)。这些生物标志物可以作为客观的临床实验室检测的基础。我们识别候选生物标记物的方法是基于人类受试者和动物模型中的遗传和基因表达研究的整合。在这一领域的试点研究中，最近发表了1(Le-Nrulescu等人)。2009)我们已经确定了一系列情绪状态的高概率血液候选生物标记基因，值得进一步研究。根据一组十大候选生物标记物(五个用于高情绪，五个用于低情绪)开发的预测分数在两个独立的患者队列中显示了对高情绪(躁狂)和低情绪(抑郁)状态的敏感性和特异性。我们的初步研究表明，血液生物标记物可能为了解大脑功能和疾病状态提供了一个出人意料的信息窗口。这项高风险、高回报的工作需要延伸和细化，这也是我们提议要做的。抑郁症和双相情感障碍等情绪障碍的临床实验室血液测试的发展将对患者的健康、福祉、生活质量和独立功能产生影响，并减少住院和总体医疗成本。鉴于美国每5个人中就有一个人一生中会患上严重的情绪障碍，这类工作的潜在医疗、社会和经济影响怎么强调都不为过。 公共卫生相关性：到目前为止，还没有针对精神疾病的客观临床实验室测试。目前依赖于不精确的诊断分类，依赖于患者对症状的自我报告和临床医生的印象，导致对这些普遍、令人痛苦和致残的疾病的诊断和治疗不够理想。此外，缺乏客观的诊断测试构成了开发新药和治疗方法的重大障碍。我们的工作旨在为这些问题提供解决方案。

项目成果

Convergent functional genomic studies of ω-3 fatty acids in stress reactivity, bipolar disorder and alcoholism.

• DOI: 10.1038/tp.2011.1
• 发表时间: 2011-04-26
• 期刊: Translational psychiatry
• 影响因子: 6.8
• 作者: Le-Niculescu H;Case NJ;Hulvershorn L;Patel SD;Bowker D;Gupta J;Bell R;Edenberg HJ;Tsuang MT;Kuczenski R;Geyer MA;Rodd ZA;Niculescu AB
• 通讯作者: Niculescu AB

Dissecting Suicidality Using a Combined Genomic and Clinical Approach.

使用基因组和临床相结合的方法剖析自杀。

• DOI: 10.1038/npp.2016.228
• 发表时间: 2017
• 期刊: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
• 作者: Niculescu,AlexanderB;Le-Niculescu,Helen
• 通讯作者: Le-Niculescu,Helen