Essential Fatty Acids In Psychiatric Disorders

精神疾病中的必需脂肪酸

• 批准号: 8941374
• 负责人: Joseph Hibbeln
• 金额: $ 46.1万
• 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/8941374
• 关键词: 16 year old; 7 year old; Accounting; Addictive Behavior; Adolescence; Adult; Aftercare; Aggressive behavior; Alcohol consumption; Alcohol dependence; Alcohol or Other Drugs use; American; Animal Model; Arachidonic Acids; Attention; Attention deficit hyperactivity disorder; Behavior; Biological; Biological Assay; Birth; Blood; Blood specimen; Brain; Brazil; Bread; Cells; Cerebrovascular Circulation; Characteristics; Child; Childhood; Chronic; Clinical; Clinical Trials; Cohort Studies; Collaborations; Conceptions; Conduct Disorder; Consumption; Coupled; Cross-Sectional Studies; Data; Depressed mood; Development; Diet; Dietary Component; Dietary Mercury; Dietary intake; Disease; Docosahexaenoic Acids; Dopamine; Drug Formulations; Endogenous depression; Enrollment; Ensure; Environment; Environmental Risk Factor; Enzymes; Essential Fatty Acids; European; Event; Fatty Acids; Fatty acid glycerol esters; Feeling suicidal; Fetus; Fishes; Food Safety; Foundations; Genes; Goals; Guidelines; Heavy Drinking; Herbal Teas; Home environment; Human Milk; Impulsive Behavior; Impulsivity; Incentives; Infant; Intake; Intervention; Life; Linear Regressions; Linoleic Acids; Longitudinal Studies; Major Depressive Disorder; Mass Spectrum Analysis; Measures; Meat; Mediating; Mental Depression; Mental Health; Mental disorders; Mercury; Meta-Analysis; Military Personnel; Modeling; Mood Disorders; Mothers; Motor; Neonatal; Nervous system structure; Neurologic; Neurotransmitters; Nutrient; Nutritional; Omega-3 Fatty Acids; Outcome; Oxidoreductase; Parents; Participant; Pathway interactions; Phenotype; Placebos; Plasma; Policies; Population Study; Positron-Emission Tomography; Postpartum Period; Pregnancy; Pregnant Women; Prevalence; Process; Production; Protocols documentation; Publications; Randomized; Reaction; Recommendation; Relative (related person); Reporting; Research Design; Residual state; Rewards; Risk; Risk Factors; Seafood; Series; Serum; Severities; Shellfish; Source; Substance abuse problem; Suicide; Symptoms; System; Techniques; Testing; Time; Tissues; Translating; Treatment Efficacy; Unsaturated Fatty Acids; Update; Variant; Veterans; Whole Blood; Wine; Withdrawal; Woman; accomplished suicide; adrenic acid; alpha-Linolenic Acid; base; cerebral atrophy; clinical efficacy; clinical practice; depressive symptoms; deviant; drinking; emerging adult; externalizing behavior; feeding; fetal; follow-up; genetic variant; grandparent; infancy; interest; neurodevelopment; neuroimaging; non-smoking; offspring; parental influence; peer; pregnant; prenatal; prevent; problem drinker; prospective; randomized placebo controlled trial; resilience; restoration; single episode major depressive disorder; skills; suicidal behavior; suicidal morbidity; suicidal risk; treatment effect

SNN conducts an integrated series of clinical projects evaluating whether restoration of adequate dietary intakes of omega-3 essential fatty acids decreases the risk for pathological phenotypes among subjects with disorders of affective or impulsivity specifically alcoholic use, depression, aggression and suicide. These studies are designed such that the findings can be readily translated into practice. SNN pioneered the hypothesis that restoring adequate omega-3 HUFAs intakes could treat or prevent major depression. We systematically evaluated clinical trials evaluating treatment efficacy of n-3 HUFAs for depressed mood in a hierarchical meta-analysis. We sought to determine why some trials reported substantial clinical efficacy and others reported variable or no effects. We found that interventions using a formulation rich in EPA (>50% EPA) reported considerable clinical benefits (Hedges g = 0.34; p = 10-7), but formulation rich in DHA (>50% DHA) displayed no clinical benefits. Crucially, we found that when study enrolled participants with significant clinical depression, considerable benefits over placebo (Hedges g = 0.86; p = 10-8); in contrast to enrolling participants who did not have significant depressive symptoms. This analysis provides the foundation for treatment recommendations for major depressive symptoms. 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. Many nutrients is seafood may have contributed to our prior finding that the 2004 FDA and EPA advisory for women to limit seafood consumption during pregnancy inadvertently creates greater risks of peer problems, poor prosocial behaviors and low verbal IQ. In order to interrogate the specific nutritional contribution of highly unsaturated omega-3 and omega-6 fats we previously utilized the Mendelian randomization of genetic variants is the FADS genes. The enzymes expressed by the FADS genes, delta 5 and delta 6 dehydrogenase, are rate limiting for the production of docosahexaenoic acid (DHA) and arachidonic acid (AA) from their precursors, alpha-linolenic acid (ALA) and linoleic acid (LA) respectively. We found 8 points lower IQ among children fed formula containing the precursor fatty acids who had the poor functioning variant, compared to formula fed children who had the functional FADS variant. We then interrogated maternal status and found that both poor functioning FADS variants and lower levels of maternal DHA and AA were associated with lower child IQ indicating a specific deficit of essential highly unsaturated fatty acids as one of the nutrients rich in fish. 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. Development of an Exposome approach. Although there is considerable evidence to suggest that environmental factors are involved in the development of many childhood and adult outcomes, it is largely agreed that events or conditions in the prenatal or infant period may have a key effect on many pathways. Increasingly attention is being concentrated on even earlier time frames, with the possible influence of parental childhood, infancy and fetal life. The aim of an exposome analysis such as this is to identify previously unsuspected associations; the technique is thus both hypothesis testing and hypothesis generating. In this study we assessed 1,755 variables characterizing the grandparents, the parents birth, childhood, adolescence and early adulthood, the environment prior to conception, during pregnancy, labor, delivery, and the neonatal period. The outcome variable was the childs motor ability as demonstrated using a test of ball skills. In this study one of the major findings concerned the mothers traumatic childhood. The unadjusted analyses showed that the offspring of mothers who had been abused physically or emotionally, those who had rated their own mothers as uncaring and/or unstable, and who had spent some time in a Childrens Home were more likely to have offspring with poor ball skills. PET study: Chronic alcohol dependence has been associated with disturbed behavior, cerebral atrophy and a low plasma concentration of docosahexaenoic acid (DHA, 22:6n-3). In animal models, excessive alcohol consumption reduces brain DHA concentration likely by excessive oxidative degredation. We compared 15 non-smoking chronic alcoholics, studied within 7 days of their last drink, to 22 non-smoking healthy controls. Using positron emission tomography (PET), we measured regional coefficients (K*) and rates (Jin) of DHA incorporation from plasma into the brain of each group using 1-11CDHA, and regional cerebral blood flow (rCBF) using 15Owater. We found significantly higher rates of incorporation for DHA into brain among alcoholics indicating a deficit of brain DHA. Higher rCBF in alcoholics suggested increased energy consumption during withdrawal.

SNN 开展了一系列综合临床项目，评估恢复足够的 omega-3 必需脂肪酸饮食摄入量是否可以降低患有情感或冲动疾病（特别是酗酒、抑郁、攻击性和自杀）的受试者的病理表型风险。 这些研究的设计使得研究结果可以很容易地转化为实践。 SNN 率先假设恢复足够的 omega-3 HUFA 摄入量可以治疗或预防重度抑郁症。我们通过分层荟萃分析系统地评估了评估 n-3 HUFA 对抑郁情绪的治疗效果的临床试验。 我们试图确定为什么一些试验报告了显着的临床疗效，而另一些试验报告了不同的效果或没有效果。我们发现，使用富含 EPA (>50% EPA) 的制剂进行干预具有相当大的临床益处 (Hedges g = 0.34；p = 10-7)，但富含 DHA (>50% DHA) 的制剂没有表现出临床益处。至关重要的是，我们发现，当研究招募患有严重临床抑郁症的参与者时，与安慰剂相比，效果显着（Hedges g = 0.86；p = 10-8）；与招募没有明显抑郁症状的参与者相反。该分析为重度抑郁症状的治疗建议提供了基础。 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。 海鲜中的许多营养素可能促成了我们之前的发现，即 2004 年 FDA 和 EPA 针对女性在怀孕期间限制海鲜消费的建议无意中造成了更大的同伴问题、不良亲社会行为和低语言智商的风险。 为了探究高度不饱和 omega-3 和 omega-6 脂肪的具体营养贡献，我们之前利用了遗传变异的孟德尔随机化，即 FADS 基因。 FADS 基因表达的酶（δ 5 和 δ 6 脱氢酶）限制从其前体 α-亚麻酸 (ALA) 和亚油酸 (LA) 生成二十二碳六烯酸 (DHA) 和花生四烯酸 (AA) 的速率分别。 我们发现，与含有功能性 FADS 变体的配方奶粉喂养的儿童相比，喂养含有前体脂肪酸的配方奶粉且具有功能性较差变体的儿童的智商低 8 个百分点。 然后，我们询问了母亲的状况，发现功能较差的 FADS 变异和母亲 DHA 和 AA 水平较低都与儿童智商较低有关，这表明必需高度不饱和脂肪酸（鱼类富含的营养物质之一）的特定缺乏。 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。 开发暴露体方法。尽管有大量证据表明环境因素与许多儿童期和成人结局的发展有关，但人们普遍认为，产前或婴儿期的事件或条件可能对许多途径产生关键影响。 越来越多的注意力集中在更早的时间范围上，这可能受到父母童年、婴儿期和胎儿期的影响。此类暴露组分析的目的是识别以前未曾怀疑的关联；因此，该技术既是假设检验又是假设生成。在这项研究中，我们评估了 1,755 个变量，这些变量描述了祖父母、父母的出生、童年、青春期和成年早期、受孕前、怀孕、临产、分娩和新生儿期的环境。结果变量是通过球技能测试证明的孩子的运动能力。 这项研究的主要发现之一涉及母亲的童年创伤。未经调整的分析表明，遭受过身体或情感虐待的母亲、那些认为自己的母亲漠不关心和/或情绪不稳定的母亲以及在儿童之家呆过一段时间的母亲更有可能生出球类较差的后代。技能。 PET 研究：慢性酒精依赖与行为紊乱、脑萎缩和二十二碳六烯酸（DHA，22:6n-3）血浆浓度低有关。在动物模型中，过量饮酒可能会因过度氧化降解而降低大脑 DHA 浓度。我们将 15 名不吸烟的慢性酗酒者与 22 名不吸烟的健康对照者进行了比较，并在他们最后一次饮酒后 7 天内进行了研究。使用正电子发射断层扫描（PET），我们使用1-11CDHA测量了各组血浆中DHA掺入大脑的区域系数（K*）和速率（Jin），并使用15O水测量了区域脑血流量（rCBF）。我们发现酗酒者大脑中 DHA 的掺入率明显较高，表明大脑 DHA 缺乏。 酗酒者较高的 rCBF 表明戒断期间能量消耗增加。