Imaging biomarkers of ECT response in major depressive disorder

重度抑郁症 ECT 反应的影像生物标志物

• 批准号: 8579531
• 负责人: Randall Espinoza
• 金额: $ 39.84万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8579531
• 关键词: Address; Aftercare; Anterior; Antidepressive Agents; Biological; Biological Markers; Blood; Blood specimen; Brain; Brain imaging; Clinical; Clinical Data; Clinical assessments; Cognitive; Corpus striatum structure; DSM-IV; Data; Diffusion; Disease; Economic Burden; Electroconvulsive Therapy; Family; Funding; Future; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Genes; Genomics; Glutamates; Goals; Health Care Costs; Health Sciences; Image; Immune response; Immune system; Individual; Inflammation; Inflammatory; Knowledge; Link; Lymphocyte; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Major Depressive Disorder; Measurement; Measures; Mental Depression; Mental disorders; Methodology; Modeling; Molecular Profiling; Moods; Multimodal Imaging; Neurobiology; Parents; Pathway interactions; Patients; Perfusion; Peripheral; Phenotype; Plasma; Pre-Clinical Model; Procedures; Process; Protons; Psychoneuroimmunology; Recruitment Activity; Relapse; Research; Research Infrastructure; Risk; Sampling; Scanning; Series; Societies; Structure; System; Testing; Therapeutic; Time; Translations; Treatment outcome; base; cost effective; cytokine; design; disability; effective therapy; experience; high risk; imaging modality; improved; indexing; inflammatory marker; innovation; meetings; neurochemistry; neuroimaging; neurotrophic factor; novel; parent project; peripheral blood; public health relevance; relating to nervous system; response; success; time interval; treatment response; treatment strategy

DESCRIPTION (provided by applicant): Major Depressive Disorder (MDD) disrupts the lives of millions of people each year and presents a substantial societal and economic burden. Despite prior research, the mechanisms underlying treatment response and relapse in MDD remain unclear. Several treatments for MDD are available, but establishing the best form of treatment can be a protracted trial and error process where some patients remain unresponsive. The parent R01 for this proposed supplement is applying a leading-edge multimodal imaging approach to identify biomarkers indexing complementary aspects of treatment-induced brain plasticity focusing on fronto-limbic and striatal circuitry in an electroconvulsive therapy (ECT) treatment model. Magnetic resonance imaging (MRI) that includes structural, functional, diffusion and perfusion imaging and MR proton magnetic resonance spectroscopy (1HMRS) is being performed at 4 time points: prior to the 1st ECT treatment, after the 2nd ECT session, 1 week after completion of the ECT index series and at 6-months post treatment when relapse will be determined. Clinical assessments are being made at two additional interval time points. Demographically similar control subjects are being imaged twice to allow estimation of the variance associated with serial assessments and to determine normalization of biomarkers in association with treatment success in MDD. Leveraging the infrastructure of the R01, intramural funding has allowed us to also obtain blood samples at each of the imaging time points for two other biologically important measures complementary to the imaging and clinical data: peripheral lymphocyte gene expression levels and psychoneuroimmunology (PNI) measures of inflammation. Analysis of the preliminary gene expression data supports the potential for these measures, when used in concert with the imaging results, to more precisely characterize the neurobiological bases of MDD and the neural processes associated with treatment success. In this supplement, we propose to extend our neuroimaging biomarker aims to also include gene expression and PNI aims. As with parent R01, the potential impact of the proposed research to science and health is large. New scientific leads may inform novel treatment approaches, identify individuals at risk for developing depression, elucidate disease-related genomic or endophenotypic factors, identify subpopulations of MDD patients who are more likely to benefit from a particular treatment, and may predictively identify patients at high risk for relapse thereb allowing for the use of alternate or more aggressive individualized treatment strategies. Longitudinal measurements of gene expression and PNI markers, in combination with neuroimaging in the context of the rapid clinical response to ECT, is an innovative approach ideally suited for charting the trajectory of mental illness to determine where, when and how to intervene.

描述（由申请人提供）：重度抑郁症（MDD）每年扰乱数百万人的生活，并带来巨大的社会和经济负担。尽管有先前的研究，但MDD治疗反应和复发的机制仍不清楚。MDD有几种治疗方法，但建立最佳治疗形式可能是一个漫长的试验和错误过程，其中一些患者仍然没有反应。该拟定补充剂的母公司R01正在应用一种前沿的多模态成像方法，以识别生物标志物，该生物标志物指示治疗诱导的脑可塑性的互补方面，重点关注电休克治疗（ECT）治疗模型中的额边缘系统和纹状体回路。在4个时间点进行磁共振成像（MRI），包括结构、功能、弥散和灌注成像以及MR质子磁共振波谱（1HMRS）：第一次ECT治疗前、第二次ECT治疗后、ECT指数系列完成后1周和治疗后6个月（确定复发时）。在另外两个间隔时间点进行临床评估。人口统计学相似的对照受试者将接受两次成像，以估计与系列评估相关的方差，并确定与MDD治疗成功相关的生物标志物的标准化。利用R01的基础设施，内部资金使我们能够在每个成像时间点获得血液样本，用于补充成像和临床数据的其他两个生物学重要指标：外周淋巴细胞基因表达水平和炎症的心理神经免疫学（PNI）指标。初步基因表达数据的分析支持这些措施的潜力，当与成像结果一起使用时，可以更精确地表征MDD的神经生物学基础和与治疗成功相关的神经过程。在本补充中，我们建议扩展我们的神经影像生物标志物目标，也包括基因表达和PNI目标。与亲本R01一样，拟定研究对科学和健康的潜在影响很大。新的科学线索可以告知新的治疗方法，识别有患抑郁症风险的个体，阐明疾病相关的基因组或内表型因素，识别更有可能从特定治疗中获益的MDD患者亚群，并可以预测性地识别复发风险高的患者，从而允许使用替代或更积极的个体化治疗策略。基因表达和PNI标记物的纵向测量，结合ECT快速临床反应背景下的神经影像学，是一种创新方法，非常适合绘制精神疾病的轨迹，以确定何时何地以及如何干预。