Central Mechanisms for Cardioprotective Behavioral Effects of W-3 Fatty Acids

描述（由申请人提供）： 大多数美国人消耗少量的长链ω-3脂肪酸，尽管临床证据表明，通过食用鱼类或鱼油补充剂增加长链-3脂肪酸的饮食摄入量可以减少主要心血管疾病（CVD）事件。此外，尽管有临床证据表明其有效性，但长链-3脂肪酸预防CVD事件的机制仍不确定。因为长链-3脂肪酸集中在脑中，并且似乎在治疗与CVD高度共病的精神障碍中具有功效，所以-3脂肪酸CVD保护可能部分源自对脑介导的心脏病行为风险因素的有益作用。根据这一建议，这项为期2年的辅助研究计划旨在增加正在进行的随机和安慰剂对照试验的数据收集，该试验是我们目前的NHLBI计划项目“心血管疾病的生物行为研究”（HL 040962）的一个组成部分。这项正在进行的试验的目的是测试增加关键-3脂肪酸-二十碳五烯酸和二十二碳六烯酸（EPA，DHA）-的摄入量对CVD预防目标的影响，包括全身炎症，心脏自主控制和两个脑介导的行为CVD风险因素：负面影响（例如，抑郁症、敌意和愤怒相关的特质），以及奖励相关的冲动决策和延迟折扣（易患损害健康的生活习惯）。为了根据汇聚的神经生物学证据来增强我们正在进行的临床试验，我们特别提出利用当代结构和功能脑成像技术来检查-3脂肪酸对涉及情感调节和冲动决策的脑系统的纵向影响。通过这种方式，拟议的研究将确定增加EPA和DHA的摄入量是否会降低（从试验前到试验后的评估）杏仁核对负面影响相关刺激的反应性，以及增加EPA和DHA的摄入量是否会降低腹侧纹状体对奖励相关刺激的反应性。最后，拟议的研究将探讨增加摄入-3脂肪酸对涉及情感和奖励相关行为的前额叶、杏仁核、海马或纹状体区域灰质形态的可能纵向影响。公共卫生相关性：ω-3脂肪酸是心血管和行为健康的必需营养素，最近的试验表明，增加ω-3脂肪酸的饮食摄入量可以预防心血管疾病事件。这项提案将通过提供结构和功能脑成像数据的纵向评估来增强我们正在进行的健康成人临床试验，使我们能够确定omega-3脂肪酸对心血管疾病的两个行为风险因素-负面影响和冲动决策（与健康行为选择相关）的潜在神经机制。

DESCRIPTION (provided by applicant): Most Americans consume low quantities of long-chain omega-3 (-3) fatty acids, despite clinical evidence that increasing dietary intake of long-chain -3 fatty acids by fish consumption or fish oil supplementation reduces major cardiovascular disease (CVD) events. Moreover, despite clinical evidence of their efficacy, the mechanisms by which long-chain -3 fatty acids protect against CVD events remain uncertain. Because long- chain -3 fatty acids are concentrated in the brain and appear to have efficacy in the treatment of psychiatric disorders that are highly co-morbid with CVD, -3 fatty acid CVD protection may derive, in part, from salutary effects on brain-mediated behavioral risk factors for heart disease. In line with this suggestion, this 2-year ancillary research plan seeks to augment data collection of an ongoing randomized and placebo-controlled trial of -3 fatty acid supplementation, which is a component of our current NHLBI Program Project, "Biobehavioral Studies of Cardiovascular Disease" (HL040962). The aims of this ongoing trial are to test the effects of increasing intake of the key -3 fatty acids - eicosapentaenoic and docosahexaenoic acids (EPA, DHA) - on targets of CVD prevention, including systemic inflammation, cardiac autonomic control, and two brain-mediated behavioral CVD risk factors: negative affect (e.g., depressive symptomatology, hostility, and anger-related traits), and reward-related impulsive decision-making and delay discounting (predisposing to health-impairing habits of lifestyle). To augment our ongoing clinical trial in light of converging neurobiological evidence, we specifically propose to utilize contemporary structural and functional brain imaging techniques to examine the longitudinal effects of -3 fatty acids on brain systems implicated in affect regulation and impulsive decision- making. In this way, the proposed research would determine if increased EPA and DHA consumption reduces (from pre-to-post trial assessments) the reactivity of the amygdala to negative affect-related stimuli, and if increased EPA and DHA consumption the reduces reactivity of the ventral striatum to reward-related stimuli. Finally, the proposed research would explore possible longitudinal effects of increased intake of -3 fatty acids on gray matter morphology in prefrontal, amygdalar, hippocampal, or striatal areas implicated in affective and reward-related behaviors. PUBLIC HEALTH RELEVANCE: Omega-3 fatty acids are essential nutrients for both cardiovascular and behavioral health, and recent trials demonstrate that increasing dietary intake of omega-3 fatty acids protects against cardiovascular disease events. This proposal would augment our ongoing clinical trial in healthy adults by providing for longitudinal assessments of structural and functional brain imaging data, enabling us to determine the potential neural mechanisms for the putative effects of omega-3 fatty acids on two behavioral risk factors for cardiovascular disease - negative affect and impulsive decision-making (as related to health behavior choices).