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: 8607600
• 负责人: Randall Espinoza
• 金额: $ 97.43万
• 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/8607600
• 关键词: Aftercare; Anatomic Models; Animals; Anisotropy; Anterior; Antidepressive Agents; Architecture; Area; Biological; 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; public health relevance; 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.

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。尽管之前有研究，MDD 治疗反应和复发的机制仍不清楚。 MDD 有多种治疗方法，但确定最佳治疗方式可能是一个漫长的反复试验过程，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了新的、独特的机会。为了加速这一领域的知识，我们建议应用领先的多模态成像方法来识别生物标志物，这些生物标志物索引治疗引起的大脑可塑性的互补方面，重点关注额叶边缘和纹状体回路。磁共振成像（MRI）将包括结构、功能、扩散和灌注成像以及MR质子磁共振波谱（1HMRS），它们共同反映与新陈代谢相关的大脑化学、形态、组织结构、静息状态活动和血流。纵向和横断面分析将确定预测治疗结果的成像生物标志物的基线因素和与治疗相关的变化，这些变化可能转化为临床环境，以指导更有效的治疗策略。电惊厥疗法 (ECT) 用于治疗难治性抑郁症，是一种既定且高效的治疗方法，可在符合条件的个体中产生快速反应。由于与心理治疗或药物治疗相比，反应发生的时间相对较短，因此 ECT 将用作治疗模型来建立治疗反应的神经生物学相关性。 MDD 患者将被前瞻性随访，以表征 ECT 相关生物反应的轨迹，预计这些反应将与其他形式的治疗重叠。将在 4 个时间点进行影像学检查：第 1 次 ECT 治疗前、第 2 次 ECT 治疗后、完成 ECT 指数系列后 1 周以及治疗后 6 个月（此时将确定复发）。将在另外两个间隔时间点进行临床评估。人口统计相似的对照受试者将被成像两次，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。拟议研究对科学和健康的潜在影响是巨大的。新的科学线索可以为新的治疗方法提供信息，识别有患抑郁症风险的个体，阐明与疾病相关的遗传或内表型因素，识别更有可能从特定治疗中受益的MDD患者亚群，并可以预测性识别高风险患者从而允许使用替代或更积极的个体化治疗策略。在 ECT 快速临床反应的背景下，多模态纵向成像是一种创新方法，非常适合绘制精神疾病的轨迹，以确定在何处、何时以及如何进行干预。