BIOBEHAVIORAL EFFECTS OF CHANGES IN PLASMA CHOLESTEROL

为了减少心脏病，目前所有美国人都被建议 以减少他们对膳食脂肪和胆固醇的消耗，以及数百万人 的人被额外开出降胆固醇的处方 通过改变饮食结构降低胆固醇的药物 被认为是不充分的。然而，胆固醇的潜在影响 人们对情绪、行为和总体幸福感的降低知之甚少。 对这些联系的研究大体上是有必要的。 医学上的谨慎，特别是因为建议进行这种干预 对于最初健康的个人来说。一种更具体的设备原理 来自最近一项胆固醇一级预防试验的荟萃分析 这表明，与对照组相比，治疗组的男性 经历了自杀和创伤死亡率的增加。这有 促使人们猜测，降低胆固醇可能与 扰乱社会功能。我们的初步研究是在 食蟹猴发现，食用低饱和食物的动物 脂肪和/或胆固醇的行为更具攻击性，表现出更低的水平 中枢神经系统5-羟色胺能活性高于饲喂高脂饲料的猴子。 与大脑5-羟色胺有关的发现可能会引起人们的兴趣， 由于5-羟色胺能功能减弱与 易怒、攻击性和自杀倾向。因此，我们提出了一个 60名男女社区居所降低胆固醇的研究 食蟹猴的受试者设计包括3个月、7个月 治疗周期：1)低脂低胆固醇饮食，仿效 目前的饮食建议；2)高脂肪和高胆固醇的饮食， 模仿典型的美国消费；3)高脂肪饮食 并辅以降胆固醇药物氯乙四胺。二 每组30只动物将被连续研究25个月。 在每个治疗期间，血浆胆固醇浓度，社会 行为(攻击性、从属和中性)、脑脊液 单胺类代谢物，以及神经、内分泌和行为 对标准挑衅的反应将得到衡量。使用这种动物 模式适用于这类调查，因为它允许：(A)精确 操纵有关的环境和饮食因素；(B)直接 观察个体的行为属性和社会行为模式 相互作用；(C)通过侵入性手段收集神经生物学数据 在人体临床研究中可行；和(D)相当于胆固醇 通过饮食和药物干预减少。

In an effort to reduce heart disease, all Americans are currently advised to reduce their consumption of dietary fat and cholesterol, and millions of individuals are additionally prescribed cholesterol-lowering medications if cholesterol reduction achieved through diet modification is deemed inadequate. However, the potential effects of cholesterol lowering on mood, behavior and general well-being are poorly understood. Research on these associations is warranted as a matter of general medical prudence, particularly because such intervention is recommended for initially healthy individuals. A more specific rationale devices from a recent meta-analysis of primary prevention trials of cholesterol lowering which indicated that, compared with controls, treated men experienced increased mortality from suicides and trauma. This has prompted speculation that cholesterol lowering may be associated with disturbances of social function. Our preliminary studies conducted on cynomolgus monkeys reveal that animals consuming diets low in saturated fat and/or cholesterol are more aggressive behaviorally and show lower CNS serotonergic activity than monkeys fed diets of high lipid content. The findings in relation to brain serotonin are of potential interest, as diminished serotonergic function has been associated with heightened irritability, aggression and suicidality. Consequently, we propose a study of cholesterol reduction among 60 socially housed, male and female cynomolgus monkeys in a within subject design involving 3, seven-month treatment periods: 1) a diet low in fat and cholesterol, modeled after current dietary recommendations; 2) a diet high in fat and cholesterol, modeled after typical American consumption; and 3) the high fat diet supplemented with the cholesterol-lowering drug, cholestyramine. Two groups of 30 animals will be studied sequentially for 25 months each. During each treatment period, plasma cholesterol concentrations, social behavior (aggressive, affiliative and neutral), cerebrospinal fluid monoaminergic metabolites, and neural, endocrine, and behavioral responses to standard provocations will be measured. Use of this animal model is appropriate in such investigation since it permits: (a)precise manipulation of pertinent environmental and dietary factors; (b) direct observation of individual behavioral attributes and patterns of social interaction; (c) collection of neurobiologic data by invasive means not feasible in human clinical studies; and (d) equivalent cholesterol reduction by dietary and pharmacologic interventions.