Imaging biomarkers of ECT response in major depressive disorder

描述(由申请人提供)：严重抑郁障碍(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。尽管之前进行了研究，但MDD治疗反应和复发的潜在机制仍不清楚。有几种治疗MDD的方法可用，但建立最佳治疗形式可能是一个旷日持久的试验和错误过程，一些患者仍然没有反应。成像技术和计算机图像分析技术的进步继续为阐明MDD的神经生物学基础和与治疗成功相关的神经过程提供新的和独特的机会。为了加速这一领域的知识，我们建议应用一种前沿的多模式成像方法来识别生物标记物，这些生物标记物索引治疗诱导的大脑可塑性的互补方面，重点是额叶边缘和纹状体回路。磁共振成像(MRI)将包括结构、功能、扩散和灌注成像和磁共振质子磁共振波谱(1HMRS)，它们共同反映大脑的化学、形态、组织结构、静息状态下的活动和与新陈代谢相关的血流。纵向和横断面分析将确定基线因素和成像生物标记物中与治疗相关的变化，预测治疗结果，可能转化为临床环境，以指导更有效的治疗策略。电休克治疗(ECT)用于治疗难治性抑郁症，是一种成熟而高效的程序，在符合条件的患者中能产生快速反应。由于与心理或药物治疗相比，反应发生的时间相对较短，ECT将被用作治疗模型，以建立治疗反应的神经生物学关联。将对MDD患者进行前瞻性跟踪，以描述与ECT相关的生物学反应的轨迹，预计这些反应将与其他形式的治疗重叠。成像将在4个时间点进行：第一次ECT治疗前，第二次ECT治疗后，ECT指数系列结束后一周，以及治疗后6个月确定复发。临床评估将在另外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，以评估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正常化。这项拟议的研究对科学和健康的潜在影响是巨大的。新的科学线索可能为新的治疗方法提供信息，识别患抑郁症的风险个体，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，并可能预测性地识别复发风险较高的患者，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图，以确定在哪里、何时和如何进行干预。

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.