Depression and Brain Metabolism

抑郁症和大脑新陈代谢

• 批准号: 6771906
• 负责人: DAN VLAD IOSIFESCU
• 金额: $ 16.54万
• 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/6771906
• 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) 申请中，候选人提议发展重度抑郁症 (MDD) 研究、治疗反应的临床评估和脑能量代谢方面的专业知识。该提案的研究部分涉及对接受西酞普兰治疗的重度抑郁症受试者进行开放、急性和前瞻性的随访。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，重度抑郁症患者的大脑中细胞高能磷代谢特征的几种化合物的水平似乎有所降低。然而，迄今为止还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治疗有反应的 MDD 受试者、抗抑郁治疗难治性 MDD 受试者以及健康志愿者。我们将使用 P-31 MRS 测量基线、治疗两周和治疗结束时磷化合物的大脑水平（以便将抗抑郁药物的大脑代谢影响与 MDD 的影响分开）。我们的目标是将大脑中高能磷化合物的水平与重度抑郁症的临床症状以及抗抑郁治疗的临床反应联系起来。这里概述的研究有可能增进我们对 MDD 病理生理学的了解。凭借 K-23 奖，候选人寻求获得以下方面的专业知识：(1) 设计和开展 MDD 临床试验，(2) 生物统计方法，以及 (3) 应用于临床试验的磁共振波谱技术。该提案中的职业发展计划包括丰富的多学科教学内容，包括哈佛大学公共卫生学院的研究设计和生物统计学、麻省理工学院的磁共振成像以及研究伦理学课程。这里概述的综合研究和职业发展计划将为候选人未来在该领域的独立调查奠定基础。一个更大规模的 R01 项目的开发将在奖励期的最后两年开始，该项目调查脑能量代谢在患有重度抑郁症的难治性受试者群体中的作用。