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（申请人提供）：本提案的总体目标是：1）制备和储存480例临床双相情感障碍患者的淋巴母细胞（LCL）和血浆，用于未来实验; 2）使用LCL表征LCL中的钙活性，以a）预测治疗结局，B）提供信息以帮助精神科医生选择最有可能对个体双相患者有效的治疗方案，以及c）有助于更可靠的双相情感障碍的有效诊断。这项研究将导致更个性化和全面有效的治疗和双相情感障碍（BD）的结果。为了实现这些目标，我们建议从参加双极CHOICE试验的患者中额外抽取血液。10个研究中心的双极CHOICE网络在2010年12月至2013年期间进行了迄今为止BD最大的前瞻性随机比较有效性研究。还将对80名健康对照受试者进行测试，以帮助区分可能与双相情感障碍诊断相关或预测治疗反应的钙测量阈值与无双相情感障碍的人中自然发生的水平。这些研究将测试基于证据的生物标志物（当受到与人类大脑功能中自然发生的化学物质类似的化学物质刺激时进行的钙实验室测试）是否可以预测对双极CHOICE研究中比较的两种情绪稳定剂（锂和奎替卡松）的反应可能性。还将研究钙检测结果，以确定其作为建立双相情感障碍有效诊断和解释双相情感障碍特征的主要干扰症状（例如，冲动、快速变化的情绪、睡眠障碍）。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。 这项拟议的连续性钙信号传导研究的独特优势在于在NIMH医疗保健研究和质量局资助的研究中使用双极CHOICE样本，该研究将提供全方位的参与者和结局，确保结果可推广到实际的临床护理。仅需要额外支付进行生物标志物钙信号研究的费用; AHRQ奖全额资助480例患者、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，并最大限度地保留，除了随机药物外，每组将有连续的个性化治疗，以管理特定的情绪状态和共病状况。 BD是一种终身、慢性和高度复发的心境障碍，其特征在于躁狂或轻躁狂发作以及抑郁发作。全谱双相情感障碍的终生患病率约为4.5%，半数患者报告在14岁时发病，遗传率估计为80%。这种高度的人类痛苦和慢性负担使双相情感障碍成为全球十大残疾原因之一，直接和间接费用估计为706亿美元 2008年，在美国。 奎替鲁与锂的双极CHOICE研究符合检测治疗有效性生物标志物的所有相关标准。这些标准包括可以通过生物标志物明确区分患者的证据，将生物标志物与所研究的疾病和治疗联系起来的证据基础，以及对一组的益处的预测。在分子水平上理解生物学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，有时被称为个性化医疗，对比较有效性研究有很大的影响。 公共卫生相关性：这项钙生物标志物研究是对400多名临床双相情感障碍患者进行的有效性比较研究的一部分，其目的是改善治疗结局的预测，帮助精神科医生选择最可能对单个双相情感障碍患者有效的治疗方案，并提高双相情感障碍诊断的有效性。这项研究将导致更个性化和全面有效的治疗和双相情感障碍的结果。