Essential Fatty Acids In Psychiatric Disorders

精神疾病中的必需脂肪酸

基本信息

批准号：
10023072
负责人：
Joseph Hibbeln
金额：
$ 92.71万
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/10023072
关键词：
Addictive Behavior Adolescence Adult Affective Alcohol consumption Alcohol or Other Drugs use American Analytical Chemistry Anterior Arachidonic Acids Attention Attention deficit hyperactivity disorder Behavior Biochemistry Biological Biological Assay Birth Blood Blood specimen Brain Brazil Bread Cells Characteristics Child Childhood Clinical Clinical Research Clinical Trials Communities Complex Conceptions Conduct Disorder Consumption Corpus striatum structure Coupled Cross-Sectional Studies Data Depressed mood Development Diet Dietary Component Dietary Mercury Dietary intake Disadvantaged Disease Docosahexaenoic Acids Dorsal Emotional Enrollment Ensure Environment Environmental Risk Factor Enzymes Epidemiology Essential Fatty Acids European Evaluation Event Fatty Acids Fatty acid glycerol esters Feeling suicidal Fetus Fishes Follow-Up Studies Food Food Safety Formulation Foundations Genes Genetic Goals Health Herbal Teas Home environment Human Milk Impulsive Behavior Impulsivity Infant Intake Intervention Lead Life Linear Regressions Linoleic Acids Longevity Longitudinal Studies Major Depressive Disorder Mass Spectrum Analysis Meat Mediating Mental Health Mental disorders Mercury Meta-Analysis Military Personnel Mission Modeling Mothers Motor Nature Nervous system structure Neurobiology Neurologic Neurosciences Neurotransmitters Nutrient Nutritional Omega-3 Fatty Acids Omega-6 Fatty Acids Outcome Oxidoreductase Parents Participant Pathway interactions Phenotype Placebos Plasma Policies Population Postpartum Period Pregnancy Pregnant Women Prevalence Prevention strategy Process Production Prospective cohort study Protocols documentation Public Policy Publications Randomized Randomized Controlled Trials Reaction Recommendation Reporting Residual state Rewards Risk Risk Factors Schools Scientist Seafood Series Serum Severities Shellfish Source Substance abuse problem Suicide System Techniques Testing Time Tissues Treatment Efficacy Unsaturated Fatty Acids Update Variant Veterans Whole Blood Wine Woman accomplished suicide addiction adrenic acid alpha-Linolenic Acid antepartum depression base career clinical efficacy clinical practice cost effective depressive symptoms deviant dietary guidelines early pregnancy emerging adult fetal financial incentive genetic variant grandparent infancy interest member mother nutrition neonatal period neurodevelopment neuroimaging novel offspring parental influence peer placebo group pregnant prenatal prevent randomized placebo controlled trial resilience response restoration single episode major depressive disorder skills sociodemographics sound study population suicidal behavior suicidal morbidity suicidal risk treatment strategy

Addictive Behavior Adolescence Adult Affective Alcohol consumption Alcohol or Other Drugs use American Analytical Chemistry Anterior Arachidonic Acids Attention Attention deficit hyperactivity disorder Behavior Biochemistry Biological Biological Assay Birth Blood Blood specimen Brain Brazil Bread Cells Characteristics Child Childhood Clinical Clinical Research Clinical Trials Communities Complex Conceptions Conduct Disorder Consumption Corpus striatum structure Coupled Cross-Sectional Studies Data Depressed mood Development Diet Dietary Component Dietary Mercury Dietary intake Disadvantaged Disease Docosahexaenoic Acids Dorsal Emotional Enrollment Ensure Environment Environmental Risk Factor Enzymes Epidemiology Essential Fatty Acids European Evaluation Event Fatty Acids Fatty acid glycerol esters Feeling suicidal Fetus Fishes Follow-Up Studies Food Food Safety Formulation Foundations Genes Genetic Goals Health Herbal Teas Home environment Human Milk Impulsive Behavior Impulsivity Infant Intake Intervention Lead Life Linear Regressions Linoleic Acids Longevity Longitudinal Studies Major Depressive Disorder Mass Spectrum Analysis Meat Mediating Mental Health Mental disorders Mercury Meta-Analysis Military Personnel Mission Modeling Mothers Motor Nature Nervous system structure Neurobiology Neurologic Neurosciences Neurotransmitters Nutrient Nutritional Omega-3 Fatty Acids Omega-6 Fatty Acids Outcome Oxidoreductase Parents Participant Pathway interactions Phenotype Placebos Plasma Policies Population Postpartum Period Pregnancy Pregnant Women Prevalence Prevention strategy Process Production Prospective cohort study Protocols documentation Public Policy Publications Randomized Randomized Controlled Trials Reaction Recommendation Reporting Residual state Rewards Risk Risk Factors Schools Scientist Seafood Series Serum Severities Shellfish Source Substance abuse problem Suicide System Techniques Testing Time Tissues Treatment Efficacy Unsaturated Fatty Acids Update Variant Veterans Whole Blood Wine Woman accomplished suicide addiction adrenic acid alpha-Linolenic Acid antepartum depression base career clinical efficacy clinical practice cost effective depressive symptoms deviant dietary guidelines early pregnancy emerging adult fetal financial incentive genetic variant grandparent infancy interest member mother nutrition neonatal period neurodevelopment neuroimaging novel offspring parental influence peer placebo group pregnant prenatal prevent randomized placebo controlled trial resilience response restoration single episode major depressive disorder skills sociodemographics sound study population suicidal behavior suicidal morbidity suicidal risk treatment strategy

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项目摘要

The Mission of the Section on Nutritional Neurosciences is to increase the understanding of how nutrients, in particular essential fats, influence risks of addictions and aberrant behaviors so as to contribute to the rational development of effective prevention and treatment strategies across the life-span. To use neuroscience, analytical chemistry, epidemiology and genetics to inform causal evaluations, such as randomized controlled trials and applied clinical research, so as to provide sound data on which new public policies can be based. To maintain an intellectual environment that optimizes and integrates the skills of diverse scientists at all stages of their careers so as to come to a sophisticated understanding of complex processes underlying the neurobiology and nature of health and disease. To lead development of cost effective and acceptable foods that can be implemented to reduce risks of addictions, affective and impulsive disorders. To create effective interfaces with large-scale systems manifesting priority needs of efficient and stable implementation members of such systems include the US Military, disadvantaged public schools, vulnerable community populations and food producers. To use these practical implementations to evaluate clinical efficacy and feasibility. Clinical findings will subsequently inform novel questions in biochemistry and neuroscience. 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-lectedfrom 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. In follow up studies, we specifically evaluated impacts and origins of maternal levels of mercury during early pregnancy (n = 4,484). We found that fish consumption explained only 7.*% of the variance in blood mercury levels. Among women who did not consume fish, higher blood levels of mercury were not predictive of offspring IQ. However, among women consuming fish, higher blood mercury levels were predictive of higher IQ among offspring. 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.

营养神经科学部分的使命是增加对营养（尤其是基本脂肪）如何影响成瘾风险和异常行为的理解，从而为整个生命中的有效预防和治疗策略的合理发展做出贡献。使用神经科学，分析化学，流行病学和遗传学来为因果评估提供信息，例如随机对照试验和应用临床研究，以提供可以基于新的公共政策的合理数据。维持一个智力环境，以优化和整合职业生涯的各个阶段的各个科学家的技能，以便对健康和疾病的神经生物学和性质的复杂过程深入了解。领导具有成本效益和可接受的食品的开发，这些食品可以降低成瘾，情感和冲动性疾病的风险。为了建立与大规模系统的有效界面，这些系统的优先需求有效，稳定的实施成员包括美国军方，处境不利的公立学校，脆弱的社区人群和食品生产者。使用这些实际实现来评估临床功效和可行性。随后，临床发现将为生物化学和神经科学方面提供新的问题。 SNN率先提出了一个假设，即恢复足够的omega-3 Hufas摄入量可以治疗或预防重度抑郁症。我们系统地评估了评估N-3 HUFA在分层荟萃分析中情绪低落的治疗功效的临床试验。我们试图确定为什么一些试验报告了实质性临床功效，而另一些试验报告了可变或没有影响。我们发现，使用富含EPA（> 50％EPA）的配方的干预措施报告了相当大的临床益处（Hedges G = 0.34; P = 10-7），但富含DHA（> 50％DHA）的配方均未显示出临床益处。至关重要的是，我们发现，当研究招募具有重大临床抑郁症的参与者时，与安慰剂相当可观（Hedges g = 0.86； p = 10-8）；与没有明显抑郁症状的参与者招生相反。该分析为重度抑郁症状的治疗建议奠定了基础。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。许多营养物质是海鲜可能有助于我们先前的发现，即2004年FDA和EPA为限制怀孕期间海鲜消费的咨询会无意间带来更大的同伴问题风险，较差的亲社会行为和低口语智商。为了询问高度不饱和omega-3和omega-6脂肪的特定营养贡献，我们先前利用了遗传变异的孟德尔随机化的是FADS基因。 FADS基因表达的酶，Delta 5和Delta 6脱氢酶是从其前体，α-烯醇酸（ALA）和亚油酸（la）的前体生产二十六六烯酸（DHA）和蛛网膜酸（AA）的速率限制。我们发现，与具有功能性FADS变体的配方奶粉儿童相比，饲喂功能较差的前体脂肪酸的儿童中，智商低8点。然后，我们询问了母体状态，发现较差的FADS变体和较低水平的母体DHA和AA都与较低的儿童智商有关，表明必需的高度不饱和脂肪酸的特定缺陷是富含鱼类的营养素之一。一个目标是量化孕产妇饮食对产前血液汞水平的贡献。全血样本和有关饮食和社会人口统计学因素的信息是从孕妇（n = 4,484）中授予的父母和儿童纵向研究（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。在后续研究中，我们专门评估了妊娠早期汞水平的影响和起源（n = 4,484）。我们发现，鱼类消耗仅解释了血液汞水平差异的7％。在不食用鱼类的妇女中，较高的血液水平没有预测后代智商。但是，在食用鱼类的女性中，较高的血液汞水平可预测后代中较高的智商。开发剥离方法。尽管有大量证据表明，环境因素与许多童年和成人结局的发展有关，但在很大程度上同意，产前或婴儿时期的事件或状况可能对许多途径产生关键影响。越来越多的关注集中在较早的时间范围上，父母童年，婴儿期和胎儿生活的可能影响。诸如此类的释放分析的目的是确定先前未知的关联；因此，该技术既是假设检验和假设产生的。在这项研究中，我们评估了祖父母，父母的出生，童年，青春期和成年早期的1,755个变量，受孕之前的环境，怀孕，劳动，分娩和新生儿时期。结果变量是使用球技能测试证明的孩子运动能力。在这项研究中，主要发现涉及母亲创伤儿童时期。未经调整的分析表明，那些在身体或情感上被虐待的母亲的后代，那些将自己的母亲评为毫无责任和/或不稳定的母亲的后代，并且在儿童家中度过了一段时间的母亲的后代更有可能具有较差的球能力。