Neuroimaging of Fatty Acids in Major Depression

描述(由申请者提供)：申请者正在寻求成为一名独立的调查者，利用正电子发射断层扫描(PET)，专注于饮食中必需的多不饱和脂肪酸(PUFAs)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低水平的omega-3PUFAs和较高的omega-6/omega-3PUFAs比率，我们的初步研究表明这些指标可以预测自杀企图。2)双盲、安慰剂对照研究发现，在抑郁症的标准治疗中加入omega-3脂肪酸(鱼油)可以改善严重抑郁症和双相情感障碍的结果。3)我们发现在自杀未遂者和低脂肪酸抑郁患者中，相似的脑区葡萄糖摄取量较低。假设：omega-3和omega-6多不饱和脂肪酸之间的功能失衡导致抑郁和自杀。目的是阐明重度抑郁症患者血浆多不饱和脂肪酸水平、临床特征(包括自杀风险)和局部脑葡萄糖代谢速率(RCMRglu)之间的关系。目的：1.在感兴趣区(ROI)，检验以下假设：a)抑郁受试者较低的rCMRglu与较低的血浆多不饱和脂肪酸相关。自杀未遂者的rCMRglu低于非自杀未遂者。目的2.对两组受试者的rCMRglu和血浆PUFA水平进行体素水平分析：a)抑郁症受试者与健康志愿者，b)有和没有自杀未遂史的抑郁症受试者。目的3.对鱼油强化治疗对rCMRglu、血浆PUFA水平、症状严重程度的影响及其相互关系进行体素水平分析。目的4.研究鱼油对血浆多不饱和脂肪酸和临床状态的影响：a)验证抑郁症患者血浆DMA水平低于健康志愿者、自杀未遂者低于非自杀未遂者的假设。B)评估总体临床状况和个别症状的严重程度。方法：30例重度抑郁障碍患者(半数有自杀未遂病史)和15例健康志愿者在服用鱼油辅助治疗4~6周前后分别进行[18F]FDG PET定量扫描。我们将对感兴趣区中的rCMRglu进行分组比较，并在体素级别使用统计参数映射来生成差异和相关映射。培训：应聘者建议从事神经成像方法学、统计学和脂质生物化学方面的专业研究。公共卫生相关性：严重抑郁障碍和自杀是世界范围内的主要公共卫生问题。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相关的新信息。

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.