Depression and Brain Metabolism

抑郁症和大脑新陈代谢

• 批准号: 6681186
• 负责人: DAN VLAD IOSIFESCU
• 金额: $ 16.21万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-03 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6681186
• 关键词: adult human (21+); antidepressants; bioenergetics; brain metabolism; citalopram; clinical research; drug resistance; high energy compound; human subject; human therapy evaluation; longitudinal human study; major depression; mental disorder chemotherapy; neuropharmacology; nuclear magnetic resonance spectroscopy; patient oriented research; phosphorus; postdoctoral investigator

DESCRIPTION (provided by applicant): In this application for an NIMH Mentored Patient-Oriented Research Career Development Award (K-23), the candidate proposes to develop expertise in the study of major depressive disorder (MDD), clinical evaluation of treatment response, and brain energy metabolism. The research component of this proposal involves an open, acute and prospective follow-up of subjects with MDD treated with citalopram. Several studies utilizing phosphorus-31 magnetic resonance spectroscopy (P31-MRS) have shown that subjects with MDD, compared with healthy volunteers, appear to have decreased brain levels of several compounds characteristic for the cellular high-energy phosphorus metabolism. However, no studies to date report measurements before and after treatment. We propose to study MDD subjects who respond to antidepressant treatment, MDD subjects refractory to antidepressant treatment, and healthy volunteers. We will use P-31 MRS to measure brain levels of phosphorus compounds at baseline, two weeks into treatment and at the end of treatment (in order to separate the brain metabolic effects of antidepressant medications from the effects of MDD). We aim to correlate brain levels of high-energy phosphorus compounds with the clinical symptoms of MDD and the clinical response to antidepressant treatment. The study outlined here has the potential to advance our knowledge on the pathophysiology of MDD. With the K-23 Award, the candidate seeks to gain expertise in: (1) designing and carrying out clinical trials for MDD, (2) biostatistical methods, and (3) magnetic resonance spectroscopy techniques as applied to clinical trials. The career development plan in this proposal includes a rich, multidisciplinary didactic component, with coursework in research design and biostatistics at the Harvard School of Public Health, magnetic resonance imaging at the Massachusetts Institute of Technology, and research ethics. The integrated research study and career development plan outlined here will lay the foundations for future independent investigation by the candidate in this area. The development of a larger scale R01 project investigating the role of brain energy metabolism in a population of treatment-resistant subjects with MDD will be started during the last two years of the award period.

描述（由申请人提供）：在NIMH指导的以患者为导向的研究职业发展奖（K-23）的申请中，候选人建议发展重性抑郁症（MDD）研究，治疗反应的临床评价和大脑能量代谢方面的专业知识。本提案的研究部分涉及对接受西酞普兰治疗的MDD受试者进行开放、急性和前瞻性随访。利用磷-31磁共振波谱（P31-MRS）的几项研究表明，与健康志愿者相比，MDD受试者似乎具有细胞高能磷代谢特征的几种化合物的脑水平降低。然而，迄今为止没有研究报告治疗前后的测量结果。我们建议研究对抗抑郁药治疗有反应的MDD受试者、抗抑郁药治疗难治的MDD受试者和健康志愿者。我们将使用P-31 MRS测量基线、治疗2周和治疗结束时磷化合物的脑水平（以将抗抑郁药物的脑代谢效应与MDD的效应分开）。我们的目的是将脑内高能磷化合物水平与MDD的临床症状和抗抑郁治疗的临床反应相关联。这里概述的研究有可能提高我们对MDD病理生理学的认识。通过K-23奖，候选人寻求获得以下方面的专业知识：（1）设计和实施MDD临床试验，（2）生物统计方法，（3）应用于临床试验的磁共振波谱技术。本提案中的职业发展计划包括丰富的多学科教学内容，包括哈佛公共卫生学院的研究设计和生物统计学课程、马萨诸塞州理工学院的磁共振成像课程以及研究伦理学课程。这里概述的综合研究学习和职业发展计划将为候选人在这一领域的未来独立调查奠定基础。在奖励期的最后两年，将开始开发一个更大规模的R 01项目，研究脑能量代谢在治疗抵抗性MDD受试者人群中的作用。