Blood Biomarkers for Psychosis: Specificity vs Overlap with Mood Disorders

描述（由申请人提供）： 我们之前已经提出并提供了证据，一种帮助识别情绪状态血液生物标志物的方法。这样的生物标志物可以作为客观的临床实验室测试的基础。我们有兴趣进行类似的研究，以确定精神病的血液生物标志物，并解决这些疾病的生物标志物之间的特异性与重叠的重要科学和临床问题。 迄今为止，没有临床实验室血液检查精神病鉴于精神障碍的复杂性，目前依赖于患者自我报告的症状和临床医生对患者的印象是一个限制速度的步骤，在提供最好的护理与现有的治疗方式，以及在开发新的和改进的治疗方法，包括新的药物。 我们建议使用融合功能基因组学（CFG）来识别生物标志物，这是我们在过去十年中开发的一种方法，该方法基于对人类和动物模型研究中基因表达和遗传数据的全面整合。我们已经提供了这种方法的原理证明，有助于鉴定情绪障碍的血液生物标志物（Le- Niculescu et al. 2009）1和最近的精神病（Kurian et al. 2011）2。在后一项工作中，我们已经确定了一系列高概率的精神病血液候选生物标志物基因，值得进一步研究。基于幻觉（精神病的关键症状）的七种顶级候选生物标志物的小组开发的预测评分在独立的患者队列中显示出良好的灵敏度和中等特异性。我们的初步研究表明，血液生物标志物可能提供了一个意想不到的信息窗口，了解大脑功能和精神病状态。 这项令人兴奋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，以获得额外的规范性数据，这也是我们在本项目中建议做的。此外，我们的候选基因列表和情绪障碍和精神病的生物标志物之间存在重叠，这表明我们需要更好地了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，探索和完善我们的疾病分类学与生物学的整合。对退伍军人医疗保健的潜在影响：精神病临床实验室血液检测的发展将导致对受精神障碍影响的退伍军人进行更有针对性的治疗，这些精神障碍涉及精神病症状，如精神分裂症和情感障碍，以及严重形式的双相情感障碍，抑郁症和创伤后应激障碍，疗效提高，副作用减少。这将对患者的健康、福祉、安全、生活质量和独立功能产生影响 降低住院率和整体医疗费用。此外，生物标志物分析可能有助于评估对治疗的反应，复发风险和早期干预措施，以防止易感个体疾病的全面发展。

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.