Neuroimaging of Fatty Acids in Major Depression

重度抑郁症中脂肪酸的神经影像学

• 批准号: 7585309
• 负责人: M Elizabeth M Sublette
• 金额: $ 17.73万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7585309
• 关键词: Affect; Arachidonic Acids; Bipolar Disorder; Brain; Brain region; Cerebrum; Characteristics; Clinical; Complex; Controlled Study; Data; Depression and Suicide; Dietary Fatty Acid; Docosahexaenoate; Double-Blind Method; Exhibits; Fatty Acids; Fish Oils; Glucose; Impulsivity; Individual; Intake; Lipid Biochemistry; Major Depressive Disorder; Maps; Membrane; Metabolic; Metabolism; Methodology; Methods; Mood Disorders; Neurobiology; Nutritional; Oils; Omega-3 Fatty Acids; Outcome; Patients; Pattern; Phospholipids; Pilot Projects; Plasma; Polyunsaturated Fatty Acids; Positron-Emission Tomography; Public Health; Recording of previous events; Reporting; Research Personnel; Role; Serotonin; Severities; Suicide; Suicide attempt; Supplementation; Symptoms; Testing; base; comparison group; depressed; depression; depressive symptoms; design; glucose metabolism; glucose uptake; healthy volunteer; improved; indexing; interest; neuroimaging; placebo controlled study; public health relevance; standard care; statistics; suicidal risk; suicide attempter

DESCRIPTION (provided by applicant): The applicant is seeking to become an independent investigator focusing on the role of dietary essential polyunsaturated fatty acids (PUFAs) in the neurobiology of mood disorders and suicide, using positron emission tomography (PET). PROJECT DESIGN: Background.- PUFAs are implicated in mood disorders: 1) Low plasma levels of omega-3 PUFAs and higher ratios of omega-6 to omega-3 PUFAs have been found among depressed patients, and our pilot study suggests these indices predict suicide attempts. 2) Double-blinded, placebo-controlled studies have found that adding omega-3 fatty acids (fish oil) to standard treatment of depression improves outcomes in Major Depressive and Bipolar Disorders. 3) We find that similar brain regions have low glucose uptake among suicide attempters and in depressed patients with low fatty acids. Hypothesis: A functional imbalance between omega-3 and omega-6 PUFAs contributes to depression and suicidality. The objective is to clarify relationships between plasma PUFA levels, clinical characteristics, including suicide risk, and regional cerebral rates of glucose metabolism (rCMRglu) in Major Depressive Disorder. Aim1. In regions of interest (ROIs), test the following hypotheses: a) Lower rCMRglu correlates with lower plasma PUFAs in depressed subjects b). rCMRglu are lower in suicide attempters vs. non-attempters. Aim 2. Perform voxel-level analyses on rCMRglu and plasma PUFA levels in: a) Depressed subjects vs. healthy volunteers, b) Depressed subjects with and without suicide attempt history. Aim 3. Perform voxel-level analyses of effects of augmentation treatment with fish oil on rCMRglu, plasma PUFA levels, symptom severity, and the relationships between them. Aim 4. Characterize the effects offish oil on plasma PUFAs and clinical status: a) Test the hypothesis that plasma levels of DMA will be lower in depressed subjects than healthy volunteers, and lower in suicide attempters than nonattempters. b) Assess overall clinical status and severity of individual symptoms. Methods: Thirty subjects with Major Depressive Disorder (half with history of suicide attempt) not responding to treatment and 15 healthy volunteers will have quantitative PET scanning with [18F]FDG before and after adjunctive treatment for 4-6 weeks with fish oil. We will perform group comparisons of rCMRglu in ROIs and use statistical parametric mapping at the voxel level to generate difference and correlational maps. TRAINING: The candidate proposes to undertake specialized studies in neuroimaging methodologies, statistics, and lipid biochemistry. PUBLIC HEALTH RELEVANCE: Major Depressive Disorder and suicide are major public health problems worldwide. This study is expected to contribute to understanding the neurobiology of depression and may provide new information relevant to treatment with dietary fatty acids.

描述（由申请人提供）：申请人正在寻求成为一名独立的研究者，专注于使用正电子发射断层扫描（PET）研究膳食必需多不饱和脂肪酸（PUFA）在情绪障碍和自杀的神经生物学中的作用。项目设计：背景。多不饱和脂肪酸与情绪障碍有关：1）在抑郁症患者中发现了低水平的omega-3多不饱和脂肪酸和较高的omega-6与omega-3多不饱和脂肪酸的比例，我们的初步研究表明，这些指数预测自杀企图。2)双盲、安慰剂对照研究发现，在抑郁症的标准治疗中加入欧米茄-3脂肪酸（鱼油）可以改善重度抑郁症和双相情感障碍的预后。3)我们发现，在自杀未遂者和低脂肪酸抑郁症患者中，相似的脑区葡萄糖摄取量较低。假设：omega-3和omega-6 PUFA之间的功能失衡导致抑郁和自杀。目的是阐明血浆PUFA水平，临床特征，包括自杀风险，和局部脑葡萄糖代谢率（rCMRglu）之间的关系，在重性抑郁症。目标1.在感兴趣区域（ROI）中，检验以下假设：a）抑郁受试者中较低的rCMRglu与较低的血浆PUFA相关B）。rCMRglu在自杀未遂者中低于非自杀未遂者。目标2.对以下受试者的rCMRglu和血浆PUFA水平进行体素水平分析：a）抑郁受试者与健康志愿者，B）有和无自杀企图史的抑郁受试者。目标3.对鱼油强化治疗对rCMRglu、血浆PUFA水平、症状严重程度以及它们之间的关系的影响进行体素水平分析。目标4。描述鱼油对血浆多不饱和脂肪酸和临床状态的影响：a）检验抑郁症受试者的血浆DMA水平低于健康志愿者，自杀者低于非自杀者的假设。B）评估总体临床状态和个体症状的严重程度。研究方法：30名对治疗无反应的重度抑郁症受试者（一半有自杀企图史）和15名健康志愿者将在鱼油连续治疗4-6周前后进行[18 F]FDG定量PET扫描。我们将在ROI中执行rCMRglu的组比较，并在体素水平上使用统计参数映射来生成差异和相关映射。培训：候选人建议从事神经影像学方法学，统计学和脂质生物化学方面的专业研究。公共卫生相关性：严重抑郁症和自杀是全球主要的公共卫生问题。这项研究有望有助于理解抑郁症的神经生物学，并可能提供与膳食脂肪酸治疗相关的新信息。