Essential Fatty Acids In Psychiatric Disorders

精神疾病中的必需脂肪酸

• 批准号: 6818483
• 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/6818483
• 关键词: aggression; alcoholism /alcohol abuse; behavior test; chemoprevention; child behavior disorders; child psychology; clinical depression; clinical trials; developmental nutrition; diet therapy; dietary lipid; homicide; human subject; human therapy evaluation; malnutrition; mental disorder chemotherapy; mental health epidemiology; nutrition related tag; omega 3 fatty acid; pathogenic diet; patient oriented research; schizophrenia; seafood; simvastatin; suicide; unsaturated fatty acids

This project examines whether inadequate dietary intakes of omega-3 essential fatty acids increases the risk for pathological behaviors associated with alcoholism, specifically depression, aggression and suicide. Randomized, placebo controlled clinical interventional trials are currently being conducted in adult populations among aggressive alcoholics, women with depression during pregnancy and suicide attempters. These studies have been stimulated by the discovery of large differences in the prevalence rates of several psychiatric disorders when comparing populations with high or low measure of seafood consumption and from examinations of omega-3 fatty acid tissue concentrations in epidemiological studies. Nutritional inadequacies during early development may leave residual neuropsychiatric deficits which contribute to an increased predisposition toward psychiatric disorders in adulthood. Developmental outcome studies are discussed below. In our ongoing clinical trial of aggressive alcoholics, the key questions are to assess if treatment with 2.8 g/d of omega-3 fatty acids will reduce 1) aggressive behaviors, 2) improve neurochemical measures of serotonergic function 3) improve cardiovascular measures thought to be associated with depressive and violent behaviors. This protocol has been actively recruiting subjects and has achieved a 100% tracking of data. Preliminary results are not available until completion when the blind is broken. In collaboration with Laure-Budens Branchey, M.D. we found that low plasma levels of DHA and AA predicted relapse among cocaine and alcohol dependent subjects over the course of two years. We have consulted on a successfully funded R0-1 grant to determine if supplementation with omega-3 fatty acids will actually reduce relapse in a randomized, controlled trial. 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. 1) 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 no 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. These 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 14,000 women enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). In a clear dose response relationship, deficient intakes were associated with nearly a doubling of the risk of depressive symptoms (EPDS >12) at 32 weeks gestation (p<1.4 X 10 -17) and 18 weeks gestation and at both 8 weeks and 8 months postpartum. Findings were robust after rigorous examination of potential confounding factors. Deficient intake of omega-3 essential fatty acids during early development may also have adverse residual effects on the behaviors of children. 1) In collaboration with the ALSPAC study, we found that deficient intake of omega-3 fatty acids during pregnancy were related to a doubling of the risk of adverse behavioral disorders among children at both 3.5 and 7 years of age. A dose response relationship predicted such parameters as increased risk of conduct disorders: fighting, lying, stealing, disobedience, which are well recognized risk factors for future sociopathic and criminal behaviors. These data are still being evaluated to determine the contribution of other variables such as socioeconomic status. We have collaborated in the submission of an R0-1 grant to prospectively capture initial drinking behavior of these children as they enter adolescence. These data can be evaluated to determine if inadequate intake during pregnancy or early childhood is a risk factor for future substance abuse. If this is identified as a risk factor, prevention studies can be planned. Since early neurodevelopmental insults have been identified as an increased risk for schizophrenia, we have examined two populations in which both plasma, obtained at birth, and 40 year clinical follow up data were available. In the first study, low plasma concentrations of essential fatty acids were unrelated to the risk of developing psychosis. Data from the second study are currently being evaluated. In a prior cross-national analysis we found higher rates of homicide mortality were correlated to lower rates of seafood consumption. In order to further refine this finding we utilized the observation that the omega-6 fatty acids from seed oils compete with omega-3 fatty acids for tissue deposition. We found that from 1950 to 2000, the increasing rates of homicide mortality were closely correlated with increasing availability omega-6 fatty acids in the food supply, in the USA, the United Kingdom, Australia and Canada. This association is also are consistent with observational and interventional data for violence and hostility published by other investigators. 2) In collaboration with Dr. Carlos Iribarren, we examined the dietary intake of omega-3 fatty acids and behavioral correlates among the 4,000 subjects in the CARDIA trial. We found that among all categories of subjects, including white men, white women, black men and black women, lower intake of DHA and other omega-3 fatty acids predicted a doubling of the risk of reporting clinically significant measures of hostility. These findings were robust after evaluation of confounding factors. 3) In an interventional trial conducted in collaboration with Dr. Muldoon at the University of Pittsburgh, subjects with hypercholesterolemia were given either Simvistatin, (a cholesterol lowering drug) or a placebo for 8 weeks. We quantified changes in mood, cognition and plasma concentrations of essential fatty acids. Treatment with Simvistatin lowered total fatty acid concentrations, but spared DHA and AA. The relationship between the sparing of these essential fatty acids and improvements or decrements in mood and cognition are still under examination. 4) We co-authored a now funded R0-1 to conduct a randomized trial of omega-3 fatty acids to reduce aggression among Thai school children. Reduction of the duration of cold and influenza infections will also be assessed and this project is currently underway.

该项目研究了Omega-3必需脂肪酸的饮食摄入是否不足会增加与酒精中毒相关的病理行为的风险，特别是抑郁症，侵略性和自杀。目前，在侵略性酗酒者，怀孕期间患有抑郁症的妇女和自杀式意见的成人人群中，目前正在安慰剂控制的临床介入试验。当比较流行病学研究中，欧米茄-3脂肪酸组织浓度的检验时，在比较了几种精神疾病的患病率的较大差异时，已经刺激了这些研究。早期发育过程中的营养不足可能会留下残留的神经精神缺陷，这有助于增加成年对精神疾病的倾向。发展结果研究将在下面讨论。 在我们正在进行的侵略性酗酒者的临床试验中，关键问题是评估2.8 g/d的omega-3脂肪酸的治疗是否会减少1）侵略性行为，2）改善血清素能功能的神经化学测量3）改善被认为与抑郁和剧烈行为相关的心血管措施。该协议一直在积极招募主题，并实现了100％的数据跟踪。直到盲人损坏时，才能获得初步结果。在与Laure-Budens Branchey合作的情况下，我们发现，DHA和AA的血浆水平较低，预测可卡因和酒精依赖受试者的复发在两年的过程中。我们已经就成功资助的R0-1赠款进行了咨询，以确定在一项随机，对照试验中补充omega-3脂肪酸是否会真正减少复发。 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。 1）从目前与亚利桑那大学的医学博士Marlene Freeman合作进行怀孕期间，抑郁症女性的Omega-3脂肪酸的公开试验可从omega-3脂肪酸进行初步数据。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，这不仅是无毒的，而且对孕妇及其婴儿具有额外的健康益处。这些发现得到了随机对照试验的跟进。这些介入试验的这些结果是从一项关于欧米茄-3脂肪酸饮食摄入妊娠期间的饮食摄入量的流行病学研究中的数据，这些研究在孕妇接受了父母和儿童（ALSPAC）的雅芳纵向研究中的近14,000名妇女中。在明确的剂量反应关系中，缺乏摄入量与妊娠32周（p <1.4 x 10 -17）和妊娠18周的抑郁症状风险（EPDS> 12）几乎增加了一倍，以及产后8周和8个月的妊娠。严格检查潜在的混杂因素后，发现很健壮。 早期发育过程中对omega-3必需脂肪酸的摄入不足也可能对儿童行为产生不利的残留影响。 1）与ALSPAC研究合作，我们发现怀孕期间对omega-3脂肪酸的摄入不足与3.5和7岁儿童不良行为障碍的风险增加了一倍。剂量反应关系预测了行为障碍风险增加的参数：战斗，撒谎，偷窃，不服从，这是未来社会病和犯罪行为的公认风险因素。仍在评估这些数据，以确定其他变量（例如社会经济状况）的贡献。我们已经合作提交了R0-1赠款，以前瞻性地捕获这些孩子进入青春期的初始饮酒行为。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。如果将其确定为危险因素，则可以计划预防研究。 由于早期的神经发育损伤已被确定为精神分裂症的风险增加，因此我们检查了两个人群，其中两个血浆在出生时获得，并且可以使用40年的临床随访数据。在第一项研究中，低血浆浓度的必需脂肪酸与患精神病的风险无关。目前正在评估第二项研究的数据。 在先前的跨国分析中，我们发现凶杀死亡率较高与较低的海鲜消耗率相关。为了进一步完善这一发现，我们利用了这样一种观察结果，即种子油的omega-6脂肪酸与omega-3脂肪酸竞争组织沉积。我们发现，从1950年到2000年，在美国，英国，澳大利亚和加拿大，凶杀死亡率的增加与欧米茄6脂肪酸的可用性增加密切相关。该关联也与其他研究人员发表的暴力和敌意的观察和介入数据一致。 2）与卡洛斯·伊里巴伦（Carlos Iribarren）博士合作，我们检查了Cardia试验中4,000名受试者之间的omega-3脂肪酸饮食摄入量和行为相关性。我们发现，在包括白人，白人妇女，黑人和黑人妇女在内的所有类别中，DHA和其他omega-3脂肪酸的摄入量较低，预测报告临床上重要的敌对措施的风险增加了一倍。评估混杂因素后，这些发现非常强大。 3）在与匹兹堡大学的Muldoon博士合作进行的一项介入试验中，对患有高胆固醇血症的受试者进行了Simvistatin（一种降低胆固醇的药物）或安慰剂的8周。我们量化了必需脂肪酸的情绪，认知和血浆浓度的变化。用近似值的治疗降低了总脂肪酸浓度，但保留了DHA和AA。这些必需脂肪酸的保留与情绪和认知减少之间的关系仍在检查中。 4）我们合着了现在资助的R0-1，对omega-3脂肪酸进行随机试验，以减少泰国小学生的侵略性。还将评估寒冷和流感感染的持续时间，目前正在进行该项目。