Neuroimaging of Fatty Acids in Major Depression

重度抑郁症中脂肪酸的神经影像学

基本信息

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
项目类别：
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

项目摘要

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）：申请人正在寻求使用正电子发射断层扫描（PET）的神经生物学神经生物学和自杀神经生物学中的饮食必需多不饱和脂肪酸（PUFA）的作用的独立研究者。项目设计：背景。-PUFA与情绪障碍有关：1）在抑郁症患者中发现了低血浆omega-3 PUFA和omega-6与omega-3 PUFA的比率较高，而我们的试点研究表明，这些指数建议这些指数预测自杀的尝试。 2）双盲，安慰剂对照的研究发现，在标准治疗抑郁症的标准治疗中添加omega-3脂肪酸（鱼油）可改善重度抑郁症和双极疾病的结果。 3）我们发现，类似的大脑区域在自杀式脂肪中和低脂肪酸抑郁症患者中的葡萄糖吸收低。假设：Omega-3和Omega-6 Pufas之间的功能失衡有助于抑郁和自杀。目的是阐明血浆PUFA水平，临床特征，包括自杀风险和葡萄糖代谢的区域大脑率（RCMRGLU）在重度抑郁症中的关系。 AIM1。在感兴趣的区域（ROI）中，检验以下假设：a）较低的rcmrglu与抑郁受试者中较低的血浆pufas相关b）。自杀案件与非生物的自杀式意见较低。 AIM 2。在以下方面对RCMRGLU和血浆PUFA水平进行体素水平分析：a）受试者与健康的志愿者，b）具有和没有自杀尝试病史的抑郁受试者。 AIM 3。对鱼油增强处理对RCMRGLU，血浆PUFA水平，症状严重程度及其之间关系的效果进行体素水平分析。 AIM 4。表征脱油对血浆PUFA的影响和临床状况：a）检验以下假设：抑郁症受试者的血浆水平将比健康的志愿者低，并且在自杀式志愿者中比非活力较低。 b）评估个人症状的总体临床状况和严重程度。方法：三十名患有重度抑郁症的受试者（一半有自杀史的史）未对治疗做出反应，15名健康志愿者将在辅助治疗前后使用[18F] FDG进行定量的PET扫描，持续4-6周的鱼油。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图。培训：候选人建议在神经影像学方法，统计和脂质生物化学方面进行专业研究。公共卫生相关性：主要的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，并可能提供与饮食脂肪酸治疗有关的新信息。