Improving Outcomes in Geriatric Depression: Magnetic Seizure Therapy

改善老年抑郁症的疗效：磁癫痫疗法

• 批准号: 8400423
• 负责人: STEFAN B ROWNY
• 金额: $ 18.56万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8400423
• 关键词: Acute; Address; Adverse effects; Aging; Amnesia; Antidepressive Agents; Area; Biometry; Bradycardia; Brain; Cardiac; Case Study; Cerebrum; Clinical; Clinical Trials Design; Cognitive; Convulsive therapy; Coronary Arteriosclerosis; Data; Dementia; Depressed mood; Development; Development Plans; Diabetes Mellitus; Dose; Drops; Elderly; Electricity; Electroconvulsive Therapy; Electrodes; Electroencephalography; Electromagnetics; Exposure to; Focal Seizure; Functional Imaging; Future; General Population; Glucose; Goals; Gold; Hamilton Rating Scale for Depression; Image; Impaired cognition; Individual; Intervention; Knowledge; Light; Limb structure; Measures; Medical; Mental Depression; Metabolic; Modality; Mood Disorders; Motor; Neurobiology; Outcome; Pattern; Pharmaceutical Preparations; Population; Randomized; Randomized Controlled Trials; Relative (related person); Reporting; Research; Research Personnel; Resistance; Risk; Safety; Scalp structure; Seizures; Severity of illness; Side; Site; Stimulus; Structure; Study of magnetics; Tachycardia; Technetium Tc 99m Exametazime; Temporal Lobe; Testing; Therapeutic; Therapeutic Effect; Training; Variant; Work; career development; clinical effect; cognitive function; cognitive reserve; cranium; design; effective intervention; effective therapy; electric field; electric impedance; evidence base; fluorodeoxyglucose positron emission tomography; geriatric depression; improved; magnetic seizure therapy; meetings; neurobiological mechanism; neuroimaging; neuromechanism; neurophysiology; novel; novel strategies; older patient; regional difference; relating to nervous system; response; risk benefit ratio; single episode major depressive disorder; single photon emission computed tomography; suicidal risk; therapy development; tool

DESCRIPTION (provided by applicant): Finding safe and effective treatments for late-life depression is imperative given the aging of the general population and the significant risk of suicide in this demographic. This K-23 application will prepare the candidate to achieve his long-term goal of developing safe and effective interventions for severe depression among the aging, guided by neurobiological mechanisms of outcomes. Elderly patients with severe medication resistant depression need viable treatment options. When medications fail, or illness severity demands emergent treatment, Electroconvulsive Therapy (ECT) remains the gold standard, but its use is limited due to risks of cognitive impairment and other side effects. This is a special concern for elderly patients with co-morbid dementia and medical illnesses. Our ability to meet this pressing need is hampered by insufficient knowledge of the neural mechanisms underlying the cognitive side effects of ECT, and a means to differentiate them from mechanisms of antidepressant action. Magnetic seizure therapy (MST) is in development as a means of reducing the cognitive side effects of ECT through a more focal seizure induction. Studies have found MST-induced seizures to be more focal, with less amnesia, but no studies in the elderly have been conducted to date. The ability to optimize MST as a less invasive but effective treatment for severe depression would be facilitated through knowledge of its mechanisms of action in comparison with ECT, though little is known about the functional neurobiological effects of MST and how they compare with ECT. Specifically, there have been no imaging studies of MST. Furthermore, focal seizure induction with MST represents a tool to study the effects of seizures related to side effects and differentiate those from mechanisms responsible for antidepressant response. Indeed, contrasting the effects of these two modalities that both induce seizures but differ so markedly in cognitive side effects presents an unparalleled opportunity to define the brain mechanisms responsible for ECT-induced amnesia. We propose to study these mechanisms with topographical EEG and FDG-PET, in a randomized controlled trial of ECT vs. MST in depressed elders. This study will provide pilot data for more extensive future work in depression in the elderly. Furthermore, this work will shed light on the mechanisms of action of the most effective treatment for depression, providing the first test of whether regional differences in the neural response to seizures result in differential clinical effects of depression and cognitive function. The career development plan is designed to enable the candidate to become a proficient, independent investigator working at the convergence of functional neuroimaging, late-life mood disorders, and neurostimulation interventions. Training in geriatric depression, brain stimulation, neurophysiology, neuroimaging, research trial design, and biostatistics will support the candidate's development into an independent investigator in the field of rational intervention development for depression in late life.

描述(由申请人提供)：鉴于人口老龄化和这一人群中自杀的重大风险，寻找安全有效的老年抑郁症治疗方法是当务之急。这一K-23应用程序将使候选人做好准备，以实现他的长期目标，即在神经生物学结果机制的指导下，为老年人中的严重抑郁症开发安全有效的干预措施。患有严重耐药抑郁症的老年患者需要可行的治疗方案。当药物无效或病情严重需要紧急治疗时，电休克治疗(ECT)仍然是黄金标准，但由于认知障碍和其他副作用的风险，其使用受到限制。这是对患有痴呆症和内科疾病的老年患者的特别关注。我们满足这一迫切需求的能力受到了阻碍，因为我们对ECT认知副作用的神经机制了解不足，以及将其与抗抑郁作用机制区分开来的方法。磁癫痫疗法(MST)是一种通过更有针对性的癫痫诱导来减少ECT的认知副作用的手段。研究发现，MST诱发的癫痫发作更有针对性，健忘症更少，但到目前为止还没有对老年人进行研究。通过了解MST与ECT相比的作用机制，将MST优化为一种侵入性较小但有效的严重抑郁症治疗方法的能力将得到促进，尽管人们对MST的功能神经生物学效应以及它们与ECT的比较知之甚少。具体地说，目前还没有关于MST的影像研究。此外，MST的局灶性癫痫诱导是一种研究与副作用相关的癫痫发作影响的工具，并将这些副作用与抗抑郁反应的机制区分开来。事实上，对比这两种模式的效果，这两种模式都会导致癫痫发作，但认知副作用差异如此之大，这为我们提供了一个无与伦比的机会，可以确定导致ECT诱发健忘症的大脑机制。我们建议在抑郁症老年人的ECT和MST的随机对照试验中，用脑电地形图和FDG-PET研究这些机制。这项研究将为今后更广泛地开展老年抑郁症的研究提供先导数据。此外，这项工作将阐明治疗抑郁症最有效的方法的作用机制，首次测试癫痫发作时神经反应的区域差异是否会导致抑郁症和认知功能的不同临床效果。职业发展计划旨在使应聘者成为一名熟练的、独立的研究员，致力于功能神经成像、晚年情绪障碍和神经刺激干预的融合。在老年抑郁症、脑刺激、神经生理学、神经成像、研究试验设计和生物统计学方面的培训将支持候选人发展成为老年抑郁症理性干预发展领域的独立调查者。