Essential Fatty Acids In Psychiatric Disorders

精神疾病中的必需脂肪酸

• 批准号: 7317398
• 负责人: JOSEPH R. HIBBELN
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7317398
• 关键词: Essential; Fatty; Acids; Psychiatric; Disorders

This project examines whether inadequate dietary intake of omega-3 essential fatty acids increases the risk for pathological behaviors among alcoholics, specifically depression, aggression and suicide. Randomized placebo-controlled clinical intervention trials continue to be conducted in adult populations of aggressive alcoholics, women with postpartum depression and among suicide attempters. In pilot analyses, treatment of alcoholics with omega-3 fatty acids reduces anger, depression and craving for alcohol. Dietary intakes that meet criteria for Recommended Daily Intakes (RDA?s) have been calculated from cross-national data sets. Large differences in the mortality rates from cardiovascular disease, stroke and all cause mortality prevalence as well as several psychiatric disorders amongst populations with high or low measures of seafood consumption. Finally, in a large epidemiological study we found that women whose seafood consumption during pregnancy were in concordance with the limits advised in 2004 by the FDA and EPA, create nutritional inadequacies for their children during the early development including low verbal IQ and deviant prosocial and peer behaviors. Chronic excessive alcohol consumption depletes brain stores of omega-3 fatty acids which are necessary for optimal neural function. In our ongoing clinical trial of aggressive alcoholics, we determine if treatment with 2.8 g/d of omega-3 fatty acids will reduce 1) aggressive behaviors, 2) improve neurochemical measures of serotonergic function as well as other neurotransmitters associate with impulsivity and alcohol use 3) reduce measures of craving 4) reduce risk of relapse. This protocol is active and has enrolled 80 subjects with 100% tracking of data. Preliminary results indicate that anger is reduced by 33% (p<0.0008) in 12 weeks and a trend towards reduction in number of relapse days (55%, p= ns). Pilot analyses also suggest a substantial reduction in craving measures. Completion of the study is estimated for autumn 2007. These findings complement a placebo controlled clinical trial conducted with collaboration with Laure-Budens Branchey, M.D., among polysubstance dependent subjects where omega-3 fatty acids reduced anger scores by 50% over 4 months. In a collaborative trial among subjects admitted to an emergency room with deliberate self harm, we found that 2 g/d of omega-3 fatty acids reduced future suicidal thinking, anger and depression scores while improving positive outlooks to life. Extending these findings to normative populations, we found that lower plasma levels of omega-3 fatty acids correlated with greater neuroticism and less agreeableness among healthy controls. In an observational trial conduced with Dr. Muldoon at the University of Pittsburgh. These data indicate that deficiencies impair affect in otherwise normal populations. Mothers can become depleted of omega-3 essential fatty acids during pregnancy when their dietary intake is inadequate. Dietary deficiencies may increase the risk of depressive symptoms for the mothers. Preliminary data is available from an open trial of omega-3 fatty acids among women with depression during pregnancy currently being conducted in collaboration with Marlene Freeman, MD at the University of Arizona. Depressive symptoms were reduced an average of 43.5 % during 8 weeks of treatment. These findings are significant as they offer a treatment for depression during pregnancy that is not only non-toxic, but has additional health benefits to pregnant women and their babies. These findings are being followed up with a randomized, controlled trial which has enrolled n=60 subjects. The results of these interventional trials were predicted from data from an epidemiological study of the dietary intake of omega-3 fatty acids during pregnancy among nearly 14,500 women enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). Findings were robust after rigorous examination of potential confounding factors. Accepted into publication in a major medical journal was our finding that concordance with the 2004 FDA and EPA advisory for women to limit seafood consumption during pregnancy inadvertently creates neurodevelopmental harm to the children. Nearly 200 confounding variables were assessed. The children of mothers who ate seafood below the limit advised had greater risks of peer problems, poor prosocial behaviors and low verbal IQ and poorer performance on British nationally administered standardized academic tests. The work was conducted in collaboration with the ALSPAC study and examined nearly 9,000 children. These data can be evaluated to determine if inadequate intake during pregnancy or early childhood is a risk factor for future substance abuse. We have collaborated with Marc Schuckit, M.D and Jean Golding, Ph.D. in designing a study to prospectively capture initial drinking behavior of these children as they enter adolescence. If this is identified as a risk factor, prevention studies can be planned. Dietary intakes that meet criteria for Recommended Daily Intakes (RDA?s) have been calculated from cross-national data sets. Dose response relationships were derived comparing greater intake of seafood and lower prevalence rates of four psychiatric disorders and lower mortality rates of eight major causes. In order to further refine this finding we utilized the observation that the omega-6 fatty acids from seed oils compete for inclusion in tissues with omega-3 fatty acids, which are rich in seafood. The amount of omega-3 fatty acids required to reduce risk of illness can be reduced 10-fold by consuming fewer omega-6 fatty acids from seed oils.

该项目旨在研究饮食中摄入不足的omega-3必需脂肪酸是否会增加酗酒者的病理行为风险，特别是抑郁症，攻击性和自杀。随机安慰剂对照的临床干预试验继续在成年酗酒者、产后抑郁症妇女和自杀未遂者中进行。在初步分析中，用omega-3脂肪酸治疗酗酒者可以减少愤怒，抑郁和对酒精的渴望。符合推荐每日摄入量（RDA？）标准的膳食摄入量s）是根据跨国数据集计算的。在海产品消费量高或低的人群中，心血管疾病、中风和全因死亡率以及几种精神疾病的死亡率差异很大。最后，在一项大型流行病学研究中，我们发现，怀孕期间食用海鲜的妇女与FDA和EPA在2004年建议的限制一致，在儿童早期发育期间造成营养不足，包括语言智商低和异常的亲社会和同伴行为。 长期过量饮酒会消耗大脑中储存的欧米茄-3脂肪酸，而欧米茄-3脂肪酸是最佳神经功能所必需的。在我们正在进行的攻击性酗酒者的临床试验中，我们确定使用2.8 g/d的omega-3脂肪酸治疗是否会减少1）攻击性行为，2）改善神经化学指标的多巴胺能功能以及与冲动和酒精使用相关的其他神经递质3）减少渴望的措施4）降低复发的风险。该方案处于激活状态，已入组80例受试者，并对数据进行了100%跟踪。初步结果表明，愤怒在12周内减少了33%（p<0.0008），复发天数有减少的趋势（55%，p= ns）。试点分析还表明，大量减少渴望的措施。这项研究估计将于2007年秋季完成。 这些发现补充了与Laure-Budens Branchey，M.D.合作进行的安慰剂对照临床试验，在多物质依赖的受试者中，omega-3脂肪酸在4个月内将愤怒分数降低了50%。 在一项针对因故意自残而被送进急诊室的受试者的合作试验中，我们发现，每天摄入2克欧米茄-3脂肪酸可以减少未来的自杀想法、愤怒和抑郁评分，同时改善积极的生活观。将这些发现扩展到正常人群，我们发现健康对照组中较低的omega-3脂肪酸血浆水平与更大的神经质和更少的宜人性相关。在匹兹堡大学马尔登博士的一项观察性试验中。这些数据表明，缺陷会损害正常人群的情感。 当母亲的饮食摄入量不足时，她们在怀孕期间可能会耗尽omega-3必需脂肪酸。饮食不足可能会增加母亲抑郁症状的风险。目前正在与亚利桑那大学的Marlene Freeman医学博士合作进行的一项在怀孕期间患有抑郁症的妇女中进行的omega-3脂肪酸开放试验的初步数据是可用的。在8周的治疗期间，抑郁症状平均减轻43.5%。这些发现意义重大，因为它们为妊娠期间的抑郁症提供了一种治疗方法，不仅无毒，而且对孕妇及其婴儿有额外的健康益处。这些发现正在通过一项随机对照试验进行随访，该试验入组了n=60例受试者。这些干预性试验的结果是根据一项流行病学研究的数据预测的，该研究对参加雅芳父母和儿童纵向研究（ALSPAC）的近14，500名妇女进行了怀孕期间omega-3脂肪酸饮食摄入量的研究。在对潜在混杂因素进行严格检查后，结果是稳健的。 在一份主要的医学杂志上发表的是我们的发现，与2004年FDA和EPA建议女性在怀孕期间限制海鲜消费的一致性无意中对儿童的神经发育造成了伤害。评估了近200个混杂变量。那些吃海鲜量低于建议限量的母亲的孩子更容易出现同伴问题、不良的亲社会行为和低语言智商，在英国国家管理的标准化学术测试中表现更差。这项工作是与ALSPAC研究合作进行的，对近9，000名儿童进行了检查。这些数据可以进行评估，以确定是否在怀孕或幼儿期摄入不足是未来药物滥用的风险因素。我们与Marc Schuckit，M.D和Jean Golding，Ph.D.合作。设计一项研究，以前瞻性地捕捉这些儿童进入青春期后的最初饮酒行为。如果这被确定为风险因素，可以计划进行预防研究。 符合推荐每日摄入量（RDA？）标准的膳食摄入量s）是根据跨国数据集计算的。剂量反应关系的推导比较更大的摄入量的海鲜和较低的患病率的四种精神疾病和较低的死亡率的八个主要原因。为了进一步完善这一发现，我们利用了这样的观察结果，即来自种子油的ω-6脂肪酸与富含海鲜的ω-3脂肪酸竞争包含在组织中。降低患病风险所需的omega-3脂肪酸的量可以通过食用更少的种子油中的omega-6脂肪酸减少10倍。