Essential Fatty Acids In Psychiatric Disorders

精神疾病中的必需脂肪酸

• 批准号: 8746459
• 负责人: Joseph Hibbeln
• 金额: $ 44.48万
• 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/8746459
• 关键词: Accounting; Addictive Behavior; Adult; Affective; Aggressive behavior; Alcohol consumption; Alcohols; Anger; Arachidonic Acids; Attention; Behavior; Benefits and Risks; Biological Assay; Blood; Blood specimen; Brain; Brazil; Bread; Cardiovascular Diseases; Caring; Cells; Characteristics; Child; Chronic; Clinical; Clinical Trials; Cognitive; Cohort Studies; Collaborations; Complement; Consumption; Controlled Clinical Trials; Coupled; Cross-Sectional Studies; Data; Data Set; Department of Defense; Depressed mood; Development; Diet; Dietary Component; Dietary Mercury; Dietary Supplementation; Dietary intake; Disease; Docosahexaenoic Acids; Doctor of Medicine; Doctor of Philosophy; Drug Formulations; Eating; Emotions; Endogenous depression; Enrollment; Epidemiologic Studies; Essential Fatty Acids; Fatty Acids; Feeling suicidal; Fetus; Fishes; Functional Magnetic Resonance Imaging; Goals; Heavy Drinking; Herbal Teas; Human Milk; Impulsivity; Intake; Intervention Trial; Linear Regressions; Longitudinal Studies; Major Depressive Disorder; Mass Spectrum Analysis; Measures; Meat; Medical; Mental Depression; Mental Health; Mental disorders; Mercury; Meta-Analysis; Military Personnel; Modeling; Mothers; Naltrexone; Nervous system structure; Neurologic; Neurophysiology - biologic function; Neurotransmitters; Nicotine; Nicotine Use Disorder; Nutritional; Nutritional status; Omega-3 Fatty Acids; Parents; Placebo Control; Placebos; Plasma; Population; Population Study; Postpartum Depression; Postpartum Period; Pregnancy; Pregnant Women; Prevalence; Process; Protocols documentation; Publications; Randomized; Reaction; Relapse; Relative (related person); Reporting; Risk; Risk Factors; Seafood; Self-Injurious Behavior; Serum; Shellfish; Source; South Carolina; Stroke; Suicide; Supplementation; Symptoms; Tissues; Treatment Efficacy; Variant; Veterans; Whole Blood; Wine; Woman; Work; adrenic acid; alcohol craving; base; cohort; craving; depressive symptoms; design; deviant; disorder later incidence prevention; double-blind placebo controlled trial; drinking; improved; medical schools; meetings; mortality; neurochemistry; neurophysiology; neuropsychological; peer; pregnant; prenatal; prevent; problem drinker; prospective; reduced substance abuse; response; single episode major depressive disorder; suicidal behavior; suicidal morbidity; suicidal risk; suicide attempter

BRAVO Study: The Better Resiliency Among Veterans with Omega-3s: A Double Blind, Placebo-Controlled Trial of Omega-3 Fatty Acid Supplementation among Military Veterans A large well designed RCT is needed to definitively determine if elevating n-3 HUFAs reduce risk of suicidal behaviors, major depressive symptoms and reduce substance abuse among a population representative of the US Military. We have recently been notified that the Department of Defense has approved $10 million to definitively evaluate if restoring adequate omega-3 fatty acid nutritional status can prevent severe suicidal behaviors and reduce addictive behaviors among US military veterans. This study will be conducted in close collaboration with Bernadette Marriott, Ph.D. at the Medical College of South Carolina. The BRAVO study seeks to determine if dietary supplementation with 3 g/d of n-3 HUFAs reduces the risk for serious suicidal behaviors, suicidal thinking, negative emotions, and symptoms associated with suicide risk, in a veteran population (n=350) at risk for suicidal behaviors. Changes in cognitive processes specific to suicide risk will be evaluated, including implicit associations, response inhibition and sustained attention. Sub-studies will evaluate efficacy in reducing depressive symptoms, alcohol and nicotine use among veterans with concomitant significant depressive symptoms, and alcohol and nicotine use disorders. In addition, a sub-study will utilize functional magnetic resonance imaging (fMRI) to evaluate the neuropsychological and neurophysiological effects. This study seeks to evaluate the efficacy of n-3 HUFAs among a representative population of US Veterans already receiving appropriate medical care so that if successful, these results can be readily applied to broader populations. The BRAVO study was conducted based upon two prior findings. First we recently evaluated the serum fatty acid status from n=800 Military suicide deaths and n=800 matched controls. We found that that all US Military personnel studied had low levels of docosahexaenoic acid and with-in this narrow range, the lowest levels were associated with a75% increase in the risk of suicide death. Second, in a previously conducted study, we found that 2 g/d of n-3 HUFAs reduced suicidal thinking by 40% among subjects with episodes of self-harm. Major depression is a risk factor for suicide. We sought to investigate sources of the heterogeneous findings reported in trials evaluating treatment efficacy of n-3 HUFAs for depressed mood. In a hierarchical meta-analysis we found that EPA predominant formulations (>50% EPA) demonstrated considerable clinical benefits (Hedges g = 0.34; p = 10-7), but DHA predominant formulations (>50% DHA) displayed no clinical benefits. Study populations with a significant clinical depression demonstrated a considerable benefit over placebo (Hedges g = 0.86; p = 10-8); unlike non-clinical populations. Identifying these factors clarified presumed inconsistencies. In previous publications we reported that lower intake of seafood and lower levels of DHA in breast milk were associated with markedly increased risks of depression during pregnancy and in the postpartum. Mothers selectively transfer DHA to their fetuses to support optimal neurological development during pregnancy. Without sufficient dietary intake, mothers can become depleted of DHA relative to n-6 HUFAs and may increase their risk of suffering major depressive symptoms and manifesting risk factors for suicide. Cross-sectional analyses were performed on data from 234 pregnant women enrolled in a prospective cohort study in Rio de Janeiro, Brazil. We found a higher likelihood of suicide risk was observed among women with higher arachidonic acid levels AA (20:4, n-6): OR=1.45, 95% CI 1.02-2.07 and adrenic acid levels AdA (22:4, n-6): OR=1.43, 95% CI 1.01-2.04. A higher likelihood of major depressive episode was also observed among women with higher AA levels OR=1.47, 95% CI 1.03-2.10 and AdA levels OR=1.59, 95% CI 1.09-2.32. Thus, higher serum levels of AA and AdA were associated with a greater likelihood of suicide risk and major depressive episode among pregnant Brazilian women. Previously we found that the 2004 FDA and EPA advisory for women to limit seafood consumption during pregnancy inadvertently creates risk of 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. The work was conducted in collaboration with the ALSPAC study and examined nearly 9,000 children. These data have formed the core of an FDA model that reevaluates both the risks and benefits of seafood consumption in pregnancy, issued 15 JAN 2009. One goal has been to quantify the contribution of components of maternal diet to prenatal blood mercury level. Whole blood samples and information on diet and sociodemographic factors were col-lected from pregnant women (n = 4,484) enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). The blood samples were assayed for total mercury using inductively coupled plasma dynamic reaction cell mass spectrometry. Linear regression was used to estimate the relative contributions of 103 dietary variables and 6 sociodemographic characteristics to whole blood total mercury levels. We estimated that maternal diet accounted for 19.8% of the total variation in total blood mercury, with 44% of diet-associated variability (8.75% of the total variation) associated with seafood consumption (white fish, oily fish, and shellfish). Other dietary components positively associated with total blood mercury included wine and herbal teas, and components with significant negative associations included white bread, meat pies or pasties, and French fries. Thus although seafood is a source of dietary mercury, seafood appeared to explain a relatively small proportion of the variation in total blood mercury in our UK study population. Our findings suggest that limiting seafood intake during pregnancy may have a limited impact on prenatal blood mercury levels. 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 associated with impulsivity and alcohol use 3) reduce measures of craving 4) reduce risk of relapse. This protocol enrolled 96 subjects with 100% tracking of data. Preliminary results indicate that anger is reduced by 33% (p<0.0008) in 12 weeks. An unexpected finding was the substantial reduction of heavy drinking days among recovering alcoholics. Those compliant with the protocol in the active group drank 3.2 days/90 while those compliant in the placebo group drank 17 days/ 90. This indicates that treatment with omega-3 fatty acids may have an effect size of 8.4. In comparison the effect size of Naltrexone, also used for relapse prevention is 0.2. These findings complement a placebo controlled clinical trial conducted with collaboration with Laure Buydens-Branchey, M.D., among polysubstance dependent subjects where omega-3 fatty acids reduced anger scores by 50% over 4 months. .

Bravo研究：欧米茄3的退伍军人之间的弹性更好：欧米茄3的双盲，安慰剂对照试验补充军事退伍军人的脂肪酸 需要大型设计的RCT，以确定提升N-3 HUFA的自杀行为的风险，重大抑郁症状并减少代表美国军方的人口中的药物滥用的风险是否降低。 最近，我们被告知，国防部已批准了1000万美元，以确定评估是否恢复足够的omega-3脂肪酸营养状况可以防止严重的自杀行为并减少美国退伍军人中的上瘾行为。 这项研究将与Bernadette Marriott博士密切合作进行。在南卡罗来纳州的医学院。 Bravo研究试图确定在退伍军人人群中，对饮食中的饮食补充3 g/d是否降低了对退伍军人人口的严重自杀行为，自杀思维，负面情绪和与自杀风险相关的症状的风险（n = 350）。 将评估特定于自杀风险的认知过程的变化，包括隐式关联，反应抑制和持续关注。子研究将评估在减轻抑郁症状，酒精和尼古丁在具有明显抑郁症状以及酒精和尼古丁使用障碍的抑郁症状，酒精和尼古丁使用方面的功效。此外，子研究将利用功能磁共振成像（fMRI）评估神经心理学和神经生理学效应。 这项研究旨在评估N-3 HUFA在已经获得适当医疗服务的美国退伍军人的代表人群中的疗效，以便如果成功，这些结果很容易被应用于更广泛的人群。 Bravo研究是根据两个先前发现进行的。首先，我们最近评估了n = 800名军事自杀死亡的血清脂肪酸状况和n = 800匹配的对照。 我们发现，所有被研究的美国军事人员的二十六烯酸酸水平较低，并且在此狭窄范围内，最低的水平与自杀死亡的风险增加了75％。其次，在先前进行的一项研究中，我们发现2 g/d的N-3 HUFA在患有自残发作的受试者中，自杀思维减少了40％。 重度抑郁症是自杀的危险因素。我们试图研究在评估N-3 Hufas治疗效果的试验中报道的异质发现的来源。 在分层荟萃分析中，我们发现EPA主要配方（> 50％EPA）表现出相当大的临床益处（Hedges G = 0.34； P = 10-7），但是DHA主要配方（> 50％DHA）没有显示出临床益处。严重临床抑郁症的研究人群表明，与安慰剂相比有很大的益处（Hedges G = 0.86; P = 10-8）;与非临床人群不同。 确定这些因素澄清了假定的矛盾。 在先前的出版物中，我们报告说，海鲜摄入量较低，而母乳中DHA水平较低与怀孕期间和产后抑郁症的风险显着增加有关。母亲有选择地将DHA转移到胎儿中，以支持怀孕期间的最佳神经发育。如果没有足够的饮食摄入，母亲可能会耗尽DHA相对于N-6 HUFA，并可能增加患有重度抑郁症状的风险，并表现出自杀的危险因素。对来自巴西里约热内卢的一项前瞻性队列研究的234名孕妇的数据进行了横断面分析。我们发现，在AA（20：4，N-6）的女性中，观察到自杀风险的可能性较高（OR = 1.45，95％CI 1.02-2.07和肾酸水平ADA（22：4，N-6）：OR = 1.43，95％CI 1.01-2.04。在较高的AA水平或= 1.47，95％CI 1.03-2.10和ADA水平和ADA水平或= 1.59，95％CI 1.09-2.32的女性中，重大抑郁发作的可能性也更高。因此，较高的血清AA和ADA水平与怀孕的巴西妇女的自杀风险和重大抑郁症的可能性更大有关。 以前，我们发现，2004年FDA和EPA妇女咨询旨在限制怀孕期间的海鲜消耗量，这无意中会对儿童造成神经发育伤害的风险。 在限制下吃海鲜的母亲的孩子面临着同伴问题，亲社会行为差和口头智商低的风险。 这项工作是与ALSPAC研究合作进行的，并检查了近9,000名儿童。这些数据构成了FDA模型的核心，该模型重新评估了2009年1月15日发布的海鲜消费的风险和益处。 一个目标是量化孕产妇饮食对产前血液汞水平的贡献。 全血样品和有关饮食和社会人口统计学因素的信息来自孕妇（n = 4,484），该孕妇参加了父母和孩子的纵向研究（ALSPAC）。使用电感耦合的血浆动态反应细胞质谱法测定血液样品用于总汞。线性回归用于估计103个饮食变量和6个社会人口统计学特征的相对贡献对全血总汞水平。我们估计，孕产妇饮食占血液总汞总变异的19.8％，其中44％的饮食相关变异性（占总变异的8.75％）与海鲜消耗有关（白鱼，油性鱼类和贝类）。其他与总血液呈正相关的饮食成分包括葡萄酒和草药茶，以及具有显着负相关的零件包括白面包，肉饼或馅饼以及炸薯条。因此，尽管海鲜是饮食汞的来源，但海鲜似乎解释了我们英国研究人群中血液汞的变化的相对较小比例。我们的发现表明，限制怀孕期间的海鲜摄入可能对产前血液汞水平的影响有限。 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酒精中毒的临床试验中，我们确定用2.8 g/d的omega-3脂肪酸治疗是否会降低1）侵略性行为，2）改善血清素能功能的神经化学测量，以及其他与脉冲和抗冲动性和酒精相关的神经递药的神经化学测量，3）降低勇气的风险4）降低风险的风险4）。 该协议招募了96名受试者，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）。一个出乎意料的发现是，康复的酗酒者大大减少了大量饮酒的日子。 那些符合活性组中的方案的人喝了3.2天/ 90，而在安慰剂组中遵守17天/ 90。 相比之下，用于预防复发的纳曲酮的效果大小为0.2。 这些发现补充了一项安慰剂对照的临床试验，该试验与多义依赖性受试者中的洛尔·布兰奇·布兰奇（Laure Buydens-Branchey）合作进行，其中omega-3脂肪酸在4个月内使愤怒得分降低了50％。 。