Calcium Study of Lymphoblasts in Bipolar Patients to Aid Diagnosis and Treatment

双相情感障碍患者淋巴细胞的钙研究有助于诊断和治疗

• 批准号: 8283631
• 负责人: CHARLES LEE BOWDEN
• 金额: $ 18.64万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-25 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8283631
• 关键词: Adverse effects; Age of Onset; Agonist; Am 80; Award; Benefits and Risks; Biological; Biological Markers; Bipolar Disorder; Blood; Blood specimen; Brain; Calcium; Calcium Signaling; Cells; Chemicals; Chronic; Circadian Rhythms; Clinical; Controlled Study; Diagnosis; Diagnostic; Direct Costs; Disease; Disease remission; Effectiveness; Facilities and Administrative Costs; Functional disorder; Funding; Future; Goals; Health Services Research; Heritability; Human; Impulsivity; Individual; Intervention; Investigation; Laboratories; Lead; Life; Link; Lithium; Lymphocyte; Major Depressive Disorder; Manic; Measurement; Measures; Medical Technology; Medicine; Mental Depression; Mental Health; Molecular; Molecular Target; Mood Disorders; Mood stabilizers; Moods; National Institute of Mental Health; Neurons; Onset of illness; Outcome; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacogenomics; Plasma; Plasma Cells; Prevalence; Process; Psychiatrist; Randomized; Recurrence; Reporting; Research; Sampling; Sensitivity and Specificity; Signal Transduction; Single Nucleotide Polymorphism; Site; Sleep disturbances; Stress; Symptoms; Test Result; Testing; Thyroid Function Tests; Treatment Effectiveness; Treatment Efficacy; Treatment Protocols; Treatment outcome; Tremor; United States; United States Agency for Healthcare Research and Quality; United States National Institutes of Health; biobank; calcium indicator; calcium metabolism; clinical care; comparative effectiveness; cost; disability; effective therapy; effectiveness research; established cell line; evidence base; expectation; health care quality; hypomania; improved; indexing; lymphoblast; lymphoblastoid cell line; meetings; non-drug; novel; prospective; quetiapine; research study; resilience; response; treatment response; valproate; volunteer

DESCRIPTION (provided by applicant): The overall aims of this proposal are to 1) prepare and store lymphoblastoid cells (LCLs) and plasma from 480 clinically ill bipolar patients for future experiments and 2) use the LCLs to characterize calcium activity in the LCLs to a) predict treatment outcomes, b) provide information to aid psychiatrists in selecting a treatment regimen most likely to be effective for an individual bipolar patient and c) contribute to more reliable an valid diagnosis of bipolar disorder. The research will result in more personalized and overall effective treatments and outcomes of bipolar disorder (BD). To accomplish these aims, we propose an additional blood draw from patients participating in the Bipolar CHOICE Trial. The 10 site Bipolar CHOICE Network is conducting between December 2010 and 2013 the largest prospective randomized comparative effectiveness study in BD to date. Eighty healthy control subjects will also be tested to aid in differentiating the threshold values of the calcium measurements that may be diagnostically associated with bipolar disorder or predictive of treatment responses from levels that occur naturally in persons without bipolar disorder. The studies will test whether evidence based biomarkers (calcium laboratory tests conducted when stimulated by chemicals similar to ones occurring naturally in human brain function) in cell lines established from a blood sample predict the likelihood of response to the two mood stabilizers (lithium and quetiapine) being compared in the Bipolar CHOICE study. The calcium test results will also be studied to determine their utility as an additional criterion in establishing a valid diagnosis of bipolar disorder and in explaining the principal disturbed symptoms that characterize bipolar disorders (e.g., impulsivity, rapidly shifting moods, sleep disturbances). Each of these objectives serves our pragmatic goal of developing more personalized treatments for bipolar disorder. A unique strength of this proposed adjunctive calcium signaling investigation resides in using the Bipolar CHOICE sample in the NIMH Agency for Healthcare Research and Quality funded study, which will provide a full spectrum of participants and of outcomes, insuring that the results will be generalizable to actual clinical care. Only the costs o conducting the biomarker calcium signaling studies will be additionally required; the AHRQ award fully funds the 480 patient, randomized, 6 month duration comparative effectiveness study. To enhance recruitment, minimize selection and volunteer bias, and maximize retention, in addition to randomized medications, each group will have adjunctive personalized treatment to manage specific mood states and comorbid conditions. BD is a lifelong, chronic and highly recurrent mood disorder characterized by episodes of mania or hypomania as well as episodes of depression. The full spectrum of bipolar disorder has a lifetime prevalence of approximately 4.5% with half of patients reporting their onset by age 14 and heritability estimated to be 80%. This high degree of human suffering and chronic burden has placed bipolar disorder among the top 10 causes of disability worldwide, with direct and indirect costs estimated to be $70.6 billion per year in 2008 dollars in the United States. The Bipolar CHOICE study of quetiapine vs. lithium meets all pertinent criteria for testing biomarkers of treatment effectiveness. These criteria include evidence that patients can be clearly differentiated by the biomarker, an evidence base linking the biomarker both to the disease and treatment studied and prediction of benefit for one group. Understanding biological differences at the molecular level could transform our ability to use and develop medical technologies more effectively, targeting interventions at more defined groups of individuals with greater precision. This potential, sometimes referred to as personalized medicine, has strong bearing on comparative effectiveness research. PUBLIC HEALTH RELEVANCE: The goals of this calcium biomarker study conducted as part of a comparative effectiveness study of over 400 clinically ill bipolar patients are to improve prediction of treatment outcomes, aid psychiatrists in selecting a treatment regimen most likely to be effective for an individual bipolar patient and improve the validity of diagnosis of bipolar disorder. The research will result in more personalized and overall effective treatments and outcomes of bipolar disorder.

描述(由申请人提供)：这项建议的总体目标是1)制备和存储480名临床双相患者的淋巴母细胞(LCL)和血浆，用于未来的实验；2)使用LCLS来表征LCLS中的钙活动，以a)预测治疗结果，b)提供信息，帮助精神科医生选择对个别双相患者最有效的治疗方案，以及c)有助于更可靠地对双相情感障碍进行有效诊断。这项研究将导致双相情感障碍(BD)的更个性化和全面有效的治疗和结果。为了实现这些目标，我们建议从参与双相选择试验的患者中额外抽血。10个地点的两极选择网络在2010年12月至2013年期间进行了迄今为止在BD进行的最大规模的前瞻性随机比较有效性研究。80名健康对照受试者也将接受测试，以帮助区分钙测量的阈值，这些阈值可能被诊断为与双相情感障碍有关，或者预测治疗反应，而不是双相情感障碍患者的自然水平。这些研究将测试从血液样本建立的细胞系中基于证据的生物标记物(在被类似于人类大脑功能的化学物质刺激时进行的钙实验室测试)是否可以预测在双相选择研究中比较的两种情绪稳定剂(锂和奎硫平)的反应可能性。钙测试结果也将被研究，以确定它们作为建立双相情感障碍的有效诊断和解释双相情感障碍特征的主要紊乱症状(例如，冲动、情绪快速变化、睡眠障碍)的额外标准的有效性。这些目标中的每一个都服务于我们开发更个性化的双相情感障碍治疗方法的务实目标。这项拟议的辅助钙信号研究的独特优势在于使用了NIMH医疗研究和质量资助研究机构中的双极选择样本，该研究将提供全方位的参与者和结果，确保结果将可推广到实际的临床护理。只有进行生物标记物钙信号研究的费用才是额外需要的；AHRQ奖完全资助了480名患者、随机、持续6个月的比较有效性研究。为了加强招募，最大限度地减少选择和志愿者偏见，并最大限度地留住患者，除了随机药物治疗外，每个组都将进行辅助的个性化治疗，以管理特定的情绪状态和共病情况。BD是一种终生的、慢性的和高度反复发作的情绪障碍，其特征是躁狂或轻躁狂症以及抑郁症的发作。双相情感障碍的全部谱系终生患病率约为4.5%，其中一半患者报告在14岁之前发病，遗传率估计为80%。这种高度的人类痛苦和长期负担已将双相情感障碍列为全球导致残疾的十大原因之一，直接和间接成本估计为706亿美元 2008年在美国每年的美元。奎硫平与锂的双极选择研究符合测试治疗有效性生物标记物的所有相关标准。这些标准包括通过生物标记物可以清楚地区分患者的证据，将生物标记物与所研究的疾病和治疗联系起来的证据基础，以及对一组人的益处的预测。在分子水平上了解生物差异可以改变我们更有效地使用和开发医疗技术的能力，以更精确的方式针对更明确的个体群体进行干预。这种潜力，有时被称为个性化药物，对比较有效性研究有很大影响。 公共卫生相关性：这项钙生物标记物研究是对400多名临床患病的双相情感障碍患者进行的比较有效性研究的一部分，其目的是改善对治疗结果的预测，帮助精神科医生选择对个人双相情感障碍患者最有效的治疗方案，并提高双相情感障碍诊断的有效性。这项研究将带来更个性化和全面有效的双相情感障碍的治疗和结果。