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: 8114776
• 负责人: Randall Espinoza
• 金额: $ 60.8万
• 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/8114776
• 关键词: Aftercare; Anatomic Models; Animals; Anisotropy; Anterior; Antidepressive Agents; Architecture; Area; Biological; Biological Markers; Biological Markers; Blood flow; Brain; Brain Chemistry; Cerebrovascular Circulation; Characteristics; Choline; Clinical; Clinical assessments; Corpus striatum structure; Coupled; Creatine; Cross-Sectional Studies; DSM-IV; Data; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Dorsal; Dysmorphology; Economic Burden; Electroconvulsive Shock; Electroconvulsive Therapy; Evaluation; Family; Fiber; Functional Magnetic Resonance Imaging; Future; Genetic; Glutamates; Goals; Health Care Costs; Health Sciences; Hippocampus (Brain); Image; Image Analysis; Imaging technology; Individual; Knowledge; Left; Link; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Major Depressive Disorder; Measurement; Measures; Mental Depression; Mental disorders; Metabolism; Methodology; Methods; Metric; Modeling; Morphology; Multimodal Imaging; N-acetylaspartate; Neurobiology; Neurophysiology - biologic function; Pathway interactions; Patients; Perfusion; Perfusion Weighted MRI; Pharmacotherapy; Procedures; Process; Protons; Psychotherapy; Refractory; Regional Perfusion; Relapse; Research; Resolution; Rest; Risk; Scanning; Series; Signal Transduction; Societies; Spin Labels; Structure; Surface; Techniques; Testing; Thalamic structure; Therapeutic; Thick; Time; Tissues; Translating; Treatment Factor; Treatment outcome; Variant; Weight; adult neurogenesis; base; blood oxygen level dependent; brain tissue; design; disorder control; effective therapy; experience; gamma-Aminobutyric Acid; high risk; improved; in vivo; indexing; innovation; interest; longitudinal analysis; meetings; morphometry; neurogenesis; novel; relating to nervous system; response; success; time interval; trait; 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. Advances in imaging technologies and in computational image analysis techniques continue to provide new and unique opportunities for elucidating the neurobiological bases of MDD and the neural processes associated with treatment success. To accelerate knowledge in this area, we propose to apply a leading-edge multimodal imaging approach to identify biomarkers indexing complementary aspects of treatment-induced brain plasticity focusing on fronto-limbic and striatal circuitry. Magnetic resonance imaging (MRI) will include structural, functional, diffusion and perfusion imaging and MR proton magnetic resonance spectroscopy (1HMRS), which jointly reflect brain chemistry, morphology, tissue architecture, resting state activity and blood flow, which is coupled to metabolism. Longitudinal and cross-sectional analyses will identify baseline factors and treatment-related changes in imaging biomarkers predictive of treatment outcome that may translate into the clinical setting to guide more effective treatment strategies. Electroconvulsive therapy (ECT), used to treat refractory depression, is an established and highly effective procedure eliciting a rapid response in eligible individuals. Since response occurs over a relatively short time period compared to psycho- or pharmacotherapy, ECT will be used as the treatment model to establish neurobiological correlates of therapeutic response. Patients with MDD will be followed prospectively to characterize the trajectories of ECT-related biological responses, which are expected to overlap those of other forms of treatment. Imaging will be 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 will be made at two additional interval time points. Demographically similar control subjects will be 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. 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 genetic 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 thereby allowing for the use of alternate or more aggressive individualized treatment strategies. Multimodal longitudinal imaging 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. PUBLIC HEALTH RELEVANCE: Depression is a commonly experienced illness that disables the lives of millions of people each year. The goal of the proposed research is to identify changes in the brain that will help us to understand why and how some people respond to treatment for depression while others do not. This knowledge may allow us to use biological markers to predict who will respond to treatment in the future and to design more effective treatments or cures that will improve the lives of patients and their families and lower health care costs to society.

描述（由申请人提供）：重度抑郁症（MDD）每年破坏数百万人的生活，并带来重大的社会和经济负担。尽管事先进行了研究，但MDD治疗反应和复发的基础机制仍不清楚。可以使用几种MDD治疗方法，但是建立最佳治疗形式可以是持久的试验和错误过程，其中一些患者仍然没有反应。成像技术和计算图像分析技术的进步继续为阐明MDD的神经生物学基础以及与治疗成功相关的神经过程提供新的独特机会。为了加速这一领域的知识，我们建议采用领先的多模式成像方法来识别生物标志物，以索引治疗引起的脑可塑性的互补方面，以额 - 夹层和纹状体电路为重点。磁共振成像（MRI）将包括结构，功能，扩散和灌注成像以及MR质子磁共振光谱（1HMR）共同反映了脑化学，形态学，组织结构，静止状态活性和血液流动，并伴随着代谢。纵向和横截面分析将确定基线因素和与治疗相关的成像生物标志物的变化，可预测治疗结果，这可能转化为临床环境，以指导更有效的治疗策略。用于治疗难治性抑郁症的电抽搐治疗（ECT）是一种已建立且高效的程序，可在合格的个体中迅速反应。由于与心理或药物疗法相比，反应发生在相对较短的时间段内，因此ECT将用作治疗模型，以建立治疗反应的神经生物学相关性。前瞻性遵循MDD的患者，以表征与ECT相关的生物学反应的轨迹，这些轨迹有望重叠其他形式的治疗。成像将在4个时间点进行：在第一个ECT治疗之前，第二个ECT疗程，在ECT指数序列完成后1周，并在确定复发后6个月后进行成像。临床评估将以两个间隔时间点进行。人口统计学上相似的对照受试者将进行两次成像，以估算与串行评估相关的方差，并确定生物标志物与MDD中治疗成功相关的归一化。拟议的研究对科学和健康的潜在影响很大。新的科学铅可能会为新颖的治疗方法提供信息，确定患有抑郁症风险的人，阐明与疾病相关的遗传或内型型因素，确定更有可能从特定治疗中受益的MDD患者的亚群，并可以预测地识别出高风险的患者，从而允许使用替代或更具侵略性的个人化治疗策略。在快速临床反应的背景下，多模式纵向成像是一种创新的方法，非常适合绘制精神疾病的轨迹，以确定何时，何时以及如何干预。 公共卫生相关性：抑郁症是一种常见的疾病，每年都会破坏数百万人的生活。拟议的研究的目的是确定大脑的变化，这将帮助我们了解某些人为什么以及如何对抑郁症的治疗做出反应，而另一些人则没有反应。这些知识可能使我们能够使用生物标记来预测谁将来会对治疗做出反应，并设计更有效的治疗方法或治疗方法，以改善患者及其家人的生活，并降低对社会的医疗保健费用。