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：服用 Omega-3 的退伍军人的恢复能力更好：退伍军人补充 Omega-3 脂肪酸的双盲、安慰剂对照试验 需要一项精心设计的大型随机对照试验来明确确定提高 n-3 HUFA 是否可以降低美国军方代表人群的自杀行为、严重抑郁症状和减少药物滥用的风险。 我们最近获悉，国防部已批准拨款 1000 万美元，以明确评估恢复足够的 omega-3 脂肪酸营养状况是否可以预防美国退伍军人的严重自杀行为并减少成瘾行为。 这项研究将与 Bernadette Marriott 博士密切合作进行。在南卡罗来纳医学院。 BRAVO 研究旨在确定膳食补充 3 克/天的 n-3 HUFA 是否可以降低退伍军人群体 (n=350) 的严重自杀行为、自杀想法、负面情绪以及与自杀风险相关的症状的风险。自杀行为的风险。 将评估自杀风险特有的认知过程的变化，包括隐性关联、反应抑制和持续注意力。子研究将评估减少伴有明显抑郁症状的退伍军人的抑郁症状、酒精和尼古丁使用以及酒精和尼古丁使用障碍的功效。此外，一项子研究将利用功能磁共振成像（fMRI）来评估神经心理学和神经生理学效应。 本研究旨在评估 n-3 HUFA 在已接受适当医疗护理的美国退伍军人代表性人群中的功效，以便如果成功，这些结果可以轻松应用于更广泛的人群。 BRAVO 研究是根据之前的两项研究结果进行的。首先，我们最近评估了 n=800 名军人自杀死亡者和 n=800 名匹配对照者的血清脂肪酸状态。 我们发现，所有研究的美国军事人员的二十二碳六烯酸水平都较低，在这个狭窄的范围内，最低水平与自杀死亡风险增加 75% 相关。其次，在之前进行的一项研究中，我们发现，每天服用 2 克 n-3 HUFA 可使有自残行为的受试者的自杀想法减少 40%。 重度抑郁症是自杀的危险因素。我们试图调查评估 n-3 HUFA 对抑郁情绪的治疗效果的试验中报告的异质性结果的来源。 在分层荟萃分析中，我们发现以 EPA 为主的配方（> 50% EPA）表现出相当大的临床益处（对冲 g = 0.34；p = 10-7），但以 DHA 为主的配方（> 50% DHA）没有表现出临床益处。具有显着临床抑郁症的研究人群表现出比安慰剂有相当大的益处（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不一致之处。 在之前的出版物中，我们报道过，海鲜摄入量较低和母乳中 DHA 含量较低与怀孕期间和产后抑郁症风险显着增加相关。母亲有选择地将 DHA 转移给胎儿，以支持怀孕期间的最佳神经系统发育。如果没有足够的饮食摄入，母亲的 DHA 相对于 n-6 HUFA 可能会耗尽，并可能增加她们遭受严重抑郁症状和表现出自杀危险因素的风险。对参加巴西里约热内卢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，花生四烯酸水平 AA（20:4，n-6）较高的女性自杀风险的可能性较高：OR=1.45，95% CI 1.02-2.07 和肾上腺酸水平 AdA（22:4，n-6）的女性自杀风险较高。 6)：OR=1.43，95% CI 1.01-2.04。 AA 水平较高 OR=1.47，95% CI 1.03-2.10 和 AdA 水平 OR=1.59，95% CI 1.09-2.32 的女性也观察到重度抑郁发作的可能性较高。因此，血清 AA 和 AdA 水平越高，巴西孕妇自杀风险和重度抑郁发作的可能性就越大。 此前我们发现，2004 年 FDA 和 EPA 针对女性怀孕期间限制海鲜消费的建议无意中给孩子带来了神经发育损害的风险。 海鲜摄入量低于建议限度的母亲的孩子，出现同伴问题、亲社会行为不良和语言智商较低的风险更大。 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。这些数据构成了 FDA 模型的核心，该模型于 2009 年 1 月 15 日发布，重新评估怀孕期间食用海鲜的风险和益处。 目标之一是量化母亲饮食成分对产前血汞水平的影响。 全血样本以及有关饮食和社会人口因素的信息是从参加雅芳父母和儿童纵向研究 (ALSPAC) 的孕妇 (n = 4,484) 中收集的。使用电感耦合等离子体动态反应池质谱法测定血液样本中的总汞。使用线性回归来估计 103 个饮食变量和 6 个社会人口特征对全血总汞水平的相对贡献。我们估计，母亲饮食占血汞总变异的 19.8%，其中 44% 的饮食相关变异（占总变异的 8.75%）与海鲜消费（白鱼、油性鱼和贝类）相关。其他与血液总汞呈正相关的饮食成分包括葡萄酒和花草茶，与显着负相关的成分包括白面包、肉馅饼或肉馅饼以及炸薯条。因此，尽管海鲜是膳食汞的来源，但在我们的英国研究人群中，海鲜似乎只能解释相对较小比例的总血汞变化。我们的研究结果表明，怀孕期间限制海鲜摄入量可能对产前血汞水平的影响有限。 长期过量饮酒会消耗脑部储存的 Omega-3 脂肪酸，而 Omega-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临床试验中，我们确定每天 2.8 克 omega-3 脂肪酸治疗是否会减少 1) 攻击性行为，2) 改善血清素能功能以及与冲动和饮酒相关的其他神经递质的神经化学指标3) 减少渴望的措施 4) 降低复发的风险。 该方案招募了 96 名受试者，并 100% 跟踪数据。 初步结果表明，12 周内愤怒减少了 33% (p<0.0008)。一个意想不到的发现是戒酒者的酗酒天数大幅减少。 活性治疗组中符合方案的参与者每 90 人喝了 3.2 天，而安慰剂组中符合协议的参与者每 90 人喝了 17 天。这表明使用 omega-3 脂肪酸治疗的效果可能为 8.4。 相比之下，也用于预防复发的纳曲酮的效果大小为 0.2。 这些发现补充了与医学博士 Laure Buydens-Branchey 合作进行的一项安慰剂对照临床试验，该试验在多物质依赖受试者中进行，其中 omega-3 脂肪酸在 4 个月内将愤怒分数降低了 50%。 。