Omega-3 Fatty Acids for Treatment of Major Depressive Disorder

描述（由申请人提供）：越来越多的临床和流行病学数据表明，omega-3 （n-3）脂肪酸在常见和致残疾病（如重度抑郁症（MDD）和心血管疾病）的病理生理学、预防和治疗中都有作用。在过去的一个世纪里，西方饮食中omega-3脂肪酸的摄入量相对于omega-6 （n-6）的摄入量急剧减少，导致omega-6与omega-3 （n-6:n-3）的比例大幅增加。与这种饮食习惯的改变相一致的是，西方社会重度抑郁症的发病率显著上升。据推测，21世纪的西方城市生活方式以高压力、少休息和大量摄入加工食品（即富含ω -6）为特征，创造了一种“促炎”倾向，可能导致一些人出现情绪障碍。正如心脏病学文献所证明的那样，omega-3可以纠正n-6:n-3的比例，并逆转这种促炎状态。最近的对照试验表明，在美国，膳食中补充omega-3脂肪酸的剂量是标准膳食摄入量的五倍或更多，可能会产生临床显著的抗抑郁和/或情绪稳定效果；然而，人们对其作用机制知之甚少。比较和对比两种主要的omega-3脂肪酸，二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）的相对抗抑郁功效的数据也很缺乏。这项为期五年的合作R01申请将主要集中在比较EPA、DHA和安慰剂单药治疗的抗抑郁疗效。我们还将研究n-3脂肪酸抗抑郁反应的潜在脂质和免疫介质和调节因子。我们的研究将是第一个在安慰剂对照的头对头试验中探讨EPA和DHA的相对抗抑郁功效的研究，也是第一个研究重性抑郁症患者脂质代谢、免疫参数和n-3膳食补充反应之间潜在的重要关系的研究。这一申请与NCCAM和NIMH领导层最近的声明是一致的，他们强调了具有“吸引力”的研究的重要性，即将生物学发现与治疗结合起来，以便对精神病学的临床实践产生直接影响。

DESCRIPTION (provided by applicant): Convergent clinical and epidemiological data have implicated omega-3 (n-3) fatty acids in the pathophysiology, prevention, and therapy of common and disabling conditions such as major depressive disorder (MDD) and cardiovascular disease. The intake of omega-3 fatty acids in the western diet has decreased dramatically relative to omega-6 (n-6) intake over the past century, causing a substantial increase in the ratio of omega-6 to omega-3 (n-6:n-3). Coincident with this change in diet, the incidence of major depressive disorder has markedly increased in western societies. It has been postulated that the 21st century western urban lifestyle characterized by high stress, little rest, and high intake of processed (i.e. omega-6- rich) foods, creates a baseline "pro-inflammatory" predisposition that may contribute to the development of mood disorders in some individuals. As has been demonstrated in the cardiology literature, omega-3 administration may correct the n-6:n-3 ratio, and reverse this pro-inflammatory state. Recent controlled trials suggest that dietary supplementation with omega-3 fatty acids at doses about five or more times the standard dietary intake in the U.S. may yield clinically significant antidepressant and/or mood stabilizing effects; however, there is little known about the mechanism of action underlying this effect. There is also a paucity of data comparing and contrasting the relative antidepressant efficacy of the two main omega-3 fatty acids, eicosapentanoic acid (EPA) and docosahexanoic acid (DHA). This five-year collaborative R01 application will focus primarily on comparing the antidepressant efficacy of monotherapy with EPA vs. DHA vs. placebo. We will also investigate potential lipid and immunological mediators and moderators of n-3 fatty acid antidepressant response. Our study will be the first to address the relative antidepressant efficacy of EPA and DHA in a placebo-controlled head-to-head trial, and also the first to investigate the potentially important relationship between lipid metabolism, immune parameters, and response to n-3 dietary supplementation in major depression. This application is consistent with recent statements from the leadership of NCCAM and NIMH, emphasizing the importance of research that has "traction," i.e. integrates biological findings with treatment in order to have a direct impact on the clinical practice of psychiatry.