Blood Biomarkers for Psychosis: Specificity vs Overlap with Mood Disorders

精神病的血液生物标志物：特异性与与情绪障碍的重叠

• 批准号: 8811010
• 负责人: Alexander B Niculescu
• 金额: --
• 依托单位: RLR VA MEDICAL 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 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8811010
• 关键词: Address; Adverse effects; Affect; Animal Model; Animals; Anxiety; Area; Biological Markers; Biology; Bipolar Disorder; Blood; Blood Tests; Brain; Candidate Disease Gene; Caring; Clinic; Clinical; Clinical Treatment; Clinical assessments; Clozapine; Complex; Data; Development; Diagnosis; Disease; Early Intervention; Future; Gene Chips; Gene Expression; Gene Expression Profiling; Genes; Genetic; Genetic study; Genomic approach; Goals; Hallucinations; Harvest; Health; Health Care Costs; Healthcare; Hospitalization; Human; Individual; Inflammatory; Interview; Laboratories; Lead; Lymphocyte; Measurement; Measures; Mental Depression; Mental disorders; Meta-Analysis; Modality; Molecular; Mood Disorders; Moods; Nature; Paper; Pathway interactions; Patient Self-Report; Patients; Peripheral; Personal Satisfaction; Pharmaceutical Preparations; Phencyclidine; Post-Traumatic Stress Disorders; Predictive Value; Probability; Psychiatry; Psychotic Disorders; Publishing; Quality of life; Recruitment Activity; Relapse; Research; Risk; Running; Safety; Sampling; Schizoaffective Disorders; Schizophrenia; Series; Severities; Solid; Source; Specificity; Study Subject; Symptoms; Testing; Time; Validation; Veterans; Visit; Whole Blood; Work; base; cohort; differential expression; disease classification; drug development; follow-up; functional genomics; human data; human subject; immune activation; impression; improved; information gathering; interest; lymphoblastoid cell line; male; peripheral blood; prevent; psychotic symptoms; public health relevance; response; trait; translational approach

DESCRIPTION (provided by applicant): We have previously proposed, and provide proof for, an approach to help identify blood biomarkers for mood state. Such biomarkers can serve as a basis for objective clinical laboratory tests. We are interested in carrying out similar studies to identify blood biomarkers for psychosis and to address the important scientific and clinical issue of specificity vs. overlap between the biomarkers for these disorders. There are to date no clinical laboratory blood tests for psychosis Given the complex nature of psychotic 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 deliverig the best possible care with existing treatment modalities, as well as in developing new and improved treatment approaches, including new medications. We propose to identify biomarkers using Convergent Functional Genomics (CFG), an approach developed by us over the last decade, which is based on comprehensive integration of gene expression and genetic data, from human and animal model studies. We have provided proof of principle for this approach helping to identify blood biomarkers for mood disorders (Le- Niculescu et al. 2009)1 and more recently for psychosis (Kurian et al. 2011)2. In that latter work, we have identified a series of high probability blood candidate biomarker genes for psychosis that deserve future scrutiny. A predictive score developed based on a panel of seven top candidate biomarkers for hallucinations (a key symptom for psychosis), shows good sensitivity and moderate specificity, in independent patient cohorts. Our preliminary studies suggest that blood biomarkers may offer an unexpectedly informative window into brain functioning and psychosis state. This exciting preliminary work needs to be carefully extended and replicated in a larger independent cohort, as well as compared to normal controls to derive additional normative data, which is what we propose to do in this project. Moreover, there was overlap between our lists of candidate genes and biomarkers for mood disorders and for psychosis, suggesting that we need to better understand the overlap between bipolar disorder and schizophrenia, and, as a field, explore and refine our integration of nosology with biology. Potential Impact on Veterans Health Care: The development of clinical laboratory blood tests for psychosis will lead to more targeted treatments for veterans affected by psychiatric disorders involving psychotic symptoms, such as schizophrenia and schizoaffective disorder, as well as severe forms of bipolar disorder, depression and PTSD, with improved efficacy and decreased side-effects. This will have an impact on patient health, well-being, safety, quality of life, and independent functioning, as well as decrease hospitalizations and overall health-care costs. Moreover, biomarker profiling may help with assessing response to treatment, risk of relapse, and early intervention efforts to prevent the full-blown development of illness in susceptible individuals.

描述(由申请人提供)： 我们之前已经提出了一种方法，并为其提供了证据，以帮助识别情绪状态的血液生物标志物。这些生物标志物可以作为客观的临床实验室检测的基础。我们有兴趣进行类似的研究，以确定精神病的血液生物标记物，并解决这些疾病的生物标记物之间的特异性与重叠这一重要的科学和临床问题。考虑到精神病的复杂性质，目前还没有针对精神病的临床实验室血液测试，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新的和改进的治疗方法，包括新药物的速度限制步骤。我们建议使用融合功能基因组学(CFG)来识别生物标记物，这是我们在过去十年中发展的一种方法，它基于从人类和动物模型研究中获得的基因表达和遗传数据的全面集成。我们已经为这种方法提供了原则证据，有助于识别情绪障碍的血液生物标记物(Le-Nulescu等人)。2009年)1和最近的精神病(Kurian等人)。在后一项工作中，我们已经确定了一系列值得未来仔细研究的精神病的高概率血液候选生物标记基因。根据幻觉(精神病的关键症状)的七个顶级候选生物标记物的小组制定的预测评分，在独立的患者队列中显示出良好的敏感性和中等的特异性。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精神状态提供了一个出人意料的信息窗口。这一激动人心的初步工作需要在更大的独立队列中仔细扩展和复制，并与正常对照进行比较，以得出更多的规范数据，这也是我们在这个项目中建议做的。此外，我们列出的情绪障碍和精神病的候选基因和生物标志物之间存在重叠，这表明我们需要更好地理解双相情感障碍和精神分裂症之间的重叠，并作为一个领域，探索和完善我们的病因学与生物学的整合。对退伍军人医疗保健的潜在影响：精神病临床实验室血液测试的发展将导致对受精神分裂症和分裂情感障碍等精神障碍以及严重形式的双相情感障碍、抑郁症和创伤后应激障碍等精神障碍影响的退伍军人进行更有针对性的治疗，从而提高疗效并减少副作用。这将对患者的健康、幸福、安全、生活质量和独立功能产生影响 随着住院人数的减少和整体医疗成本的降低。此外，生物标记物分析可能有助于评估治疗反应、复发风险以及早期干预努力，以防止易感个体疾病的全面发展。