Essential Fatty Acids In Psychiatric Disorders

精神疾病中的必需脂肪酸

• 批准号: 7591923
• 负责人: JOSEPH R. HIBBELN
• 金额: $ 39.93万
• 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/7591923
• 关键词: Accident and Emergency department; Adolescence; Adult; Affect; Aggressive behavior; Alcohol consumption; Anger; Arizona; Behavior; Brain; British; Cardiovascular Diseases; Centers for Disease Control and Prevention (U.S.); Child; Chronic; Clinical; Clinical Trials; Collaborations; Complement; Consumption; Controlled Clinical Trials; Daily; Data; Data Set; Development; Dietary intake; Doctor of Medicine; Doctor of Philosophy; Dose; Eating; Enrollment; Epidemiologic Studies; Essential Fatty Acids; Feeling suicidal; Funding; Future; Health Benefit; Heavy Drinking; Heavy Metals; Impulsivity; Intake; Intervention Trial; Life; Longitudinal Studies; Low Prevalence; Malnutrition; Measures; Mental Depression; Mental Health; Mental disorders; Mercury; Mothers; National Institute on Alcohol Abuse and Alcoholism; Nervous system structure; Neurophysiology - biologic function; Neurotic Disorders; Neurotransmitters; Numbers; Nutritional; Oils; Omega-3 Fatty Acids; Omega-6 Fatty Acids; Parents; Performance; Placebo Control; Plasma; Population; Postpartum Depression; Pregnancy; Pregnant Women; Prevalence; Prevention; Protocols documentation; Publications; Randomized; Randomized Controlled Trials; Rate; Relapse; Risk; Risk Factors; Score; Seafood; Seeds; Self-Injurious Behavior; Stroke; Substance abuse problem; Suicide; Testing; Tissues; Toxic effect; United States Environmental Protection Agency; United States Food and Drug Administration; Universities; Week; Woman; Work; alcohol craving; collaborative trial; craving; day; depressive symptoms; design; deviant; drinking behavior; early childhood; follow-up; improved; mortality; neurochemistry; peer; problem drinker; response; trend

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 96 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. The study has completed enrollemtn and is under analysis. 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. In a major publication we found that the 2004 FDA and EPA advisory for women to limit seafood consumption during pregnancy inadvertently creates neurodevelopmental harm to the children. 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. We have recieved funding and begun analyses of plasma for trace heavy metals including methyl-mercury in order to compare the benifits of reducing possible toxicity with the risks of inducing nutritional deficiencies. These analyses are being conduced in collaboration with Robert Jones o f the CDC, Spencer Garrett, NOAA and Norman Salem, Jr. NIAAA Dietary intakes that meet criteria for Recommended Daily Intakes (RDAs) 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.

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96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。该研究已完成入组并正在分析中。 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。 在一份重要的出版物中，我们发现2004年FDA和EPA建议妇女在怀孕期间限制海鲜消费，无意中对儿童的神经发育造成了伤害。 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，则可以计划进行预防研究。 我们已收到资金，并开始分析血浆中的痕量重金属，包括甲基汞，以便比较减少可能的毒性的好处和引起营养不良的风险。 这些分析是与疾病预防控制中心的罗伯特·琼斯、斯宾塞加勒特、国家海洋和大气管理局和小诺曼·塞勒姆合作进行的。NIAAA 符合推荐每日摄入量（RDA）标准的膳食摄入量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。