Essential Fatty Acids In Psychiatric Disorders

精神疾病中的必需脂肪酸

基本信息

批准号：
7732101
负责人：
JOSEPH R. HIBBELN
金额：
$ 40.87万
依托单位：
NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
依托单位国家：
美国
项目类别：
财政年份：
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/7732101
关键词：
Accident and Emergency department Acids Admission activity Adolescence Adult Affect Affective Aggressive behavior Alcohol consumption Alcohols Anger Arizona Behavior Brain British Cardiovascular Diseases Child Chronic Clinical Clinical Trials Cohort Studies Collaborations Complement Consumption Controlled Clinical Trials Daily Data Data Set Development Dietary intake Disease Doctor of Medicine Doctor of Philosophy Dose Eating Enrollment Epidemiologic Studies Essential Fatty Acids Feeling suicidal Future Health Benefit Heavy Drinking Impulsivity Intake Intervention Trial Life Longitudinal Studies Low Prevalence Malnutrition Measures Mental Depression Mental Health Mental disorders Mothers 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 United States Environmental Protection Agency United States Food and Drug Administration Universities Week Woman Work alcohol craving cerebral atrophy cohort collaborative trial craving day depressive symptoms design deviant drinking behavior early childhood follow-up improved mortality neurochemistry peer problem drinker response trend

项目摘要

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. Greater omega-3 fattty acid plasma status on admission correlated with less brain atrophy indicating that these fatty may protect from alcohol induced brain atrophy. The study has completed enrollemnt 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. Dietary intakes that meet criteria for Recommended Daily Intakes (RDAs) have been calculated from two spopurces of data: cross-national data sets and the ALSPAC cohort study. 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.

慢性过度饮酒耗尽了最佳神经功能所需的omega-3脂肪酸的脑储存。在我们正在进行的侵略性酗酒者的临床试验中，我们确定用2.8 g/d的omega-3脂肪酸治疗是否会减少1）侵略性行为，2）改善5-5-2）的神经化学措施，以及其他神经递质功能以及其他神经递质的脉冲和脉冲和酒精饮酒的关联的方法3）降低了掠夺的措施4）降低风险的风险4）。该协议是有效的，并且已经招募了96名受试者，并具有100％跟踪数据的受试者。初步结果表明，愤怒在12周内降低了33％（p <0.0008），以及减少复发天数（55％，p = ns）的趋势。试点分析还表明，渴望措施大大减少。入院时较高的omega-3节酸血浆状态与较少的脑萎缩相关，表明这些脂肪可能可以保护酒精诱导的脑萎缩。该研究已完成注册者，并正在分析。这些发现补充了一项安慰剂对照临床试验，该试验与洛尔·布登斯（Laure-Budens Branchey），医学博士（M.D. 在接受有意自我伤害的急诊室的受试者之间的合作试验中，我们发现2 g/d的Omega-3脂肪酸减少了未来的自杀思维，愤怒和抑郁得分，同时改善了积极的生活方式。将这些发现扩展到规范种群，我们发现较低的血浆水平与健康对照中的神经质较大，较少的糖尿病相关。在匹兹堡大学的Muldoon博士进行的一项观察性试验中。这些数据表明缺乏障碍在原本正常人群中受到影响。当母亲饮食摄入不足时，母亲在怀孕期间会耗尽omega-3的必要脂肪酸。饮食不足可能会增加母亲的抑郁症状风险。可以从目前与亚利桑那大学的马里兰州玛琳·弗里曼（Marlene Freeman）合作进行抑郁症的女性的Omega-3脂肪酸的开放试验获得初步数据。在治疗8周期间，抑郁症状平均降低了43.5％。这些发现很重要，因为它们在怀孕期间为抑郁症提供治疗，不仅无毒，而且对孕妇及其婴儿具有额外的健康益处。这些发现是由随机，对照试验进行的，该试验已注册n = 60个受试者。这些介入试验的结果是从妊娠期间欧米茄3脂肪酸饮食摄入量摄入的近14,500名妇女的饮食摄入量的流行病学研究中预测的。严格检查潜在的混杂因素后，发现很健壮。在一份主要出版物中，我们发现2004年FDA和EPA妇女咨询限制怀孕期间的海鲜消费量会无意中对儿童造成神经发育伤害。在限制范围内吃海鲜的母亲的孩子面临更大的同伴问题，亲社会行为差，口头智商低的孩子，以及在英国国家管理的标准化学术测试方面的表现较差。这项工作是与ALSPAC研究合作进行的，并检查了近9,000名儿童。可以评估这些数据以确定怀孕期间或幼儿期间摄入量不足是滥用药物的危险因素。我们已经与Marc Schuckit，M.D和Jean Golding博士合作。在设计一项研究以前瞻性地捕获这些儿童进入青春期的初始饮酒行为时。如果将其确定为危险因素，则可以计划预防研究。符合推荐日常摄入标准（RDA）标准的饮食摄入量是根据两个数据分入计算的：跨国数据集和ALSPAC队列研究。剂量反应关系得出，比较了四种精神疾病的海鲜摄入量和较低的患病率，并降低了八个主要原因的死亡率。为了进一步完善这一发现，我们利用了这样一种观察结果，即从种子油中的omega-6脂肪酸竞争含有富含海鲜的omega-3脂肪酸的组织中。通过减少种子油中较少的omega-6脂肪酸，可以降低降低疾病风险所需的omega-3脂肪酸量。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Increasing homicide rates and linoleic acid consumption among five Western countries, 1961-2000.

1961-2000 年五个西方国家凶杀率和亚油酸消耗量的增加。

DOI：
10.1007/s11745-004-1349-5
发表时间：
2004
期刊：
Lipids
影响因子：
1.9
作者：
Hibbeln,JosephR;Nieminen,LeviRG;Lands,WilliamEM
通讯作者：
Lands,WilliamEM

From homicide to happiness--a commentary on omega-3 fatty acids in human society. Cleave Award Lecture.

从杀人到幸福——评Omega-3脂肪酸在人类社会中的作用

DOI：
10.1177/026010600701900204
发表时间：
2007
期刊：
Nutrition and health (Berkhamsted, Hertfordshire)
影响因子：
0
作者：
Hibbeln,JosephR
通讯作者：
Hibbeln,JosephR

Seafood consumption and homicide mortality. A cross-national ecological analysis.

海鲜消费和凶杀死亡率。

DOI：
10.1159/000059747
发表时间：
2001
期刊：
World review of nutrition and dietetics
影响因子：
0
作者：
Hibbeln,JR
通讯作者：
Hibbeln,JR

The Lancet and the Royal Society are both right and wrong.

《柳叶刀》和英国皇家学会的说法既对又错。

DOI：
10.1016/s0140-6736(05)67172-3
发表时间：
2005
期刊：
Lancet (London, England)
影响因子：
0
作者：
Crawford,MichaelA;Ghebremeskel,Kebreab;Hibbeln,JosephR;House,Simon;Hunter,David;Morley,DavidC;Nicholson,Paul;Stuart,Kenneth
通讯作者：
Stuart,Kenneth

Cultural symbolism of fish and the psychotropic properties of omega-3 fatty acids.

鱼的文化象征意义和 omega-3 脂肪酸的精神作用。