In an effort to reduce risk of coronary heart disease, the National Cholesterol Education Program advises all Americans to adopt diets restricting cholesterol and fat intake. However, the potential impact of cholesterol reduction on patient well-being and neurobehavioral functioning is unknown. As such intervention is now recommended as national health policy, efforts to detect any significant behavioral sequelae of cholesterol modification are clearly warranted. Additional rationale for studying effects of cholesterol reduction on mood and neurobehavioral function derives from quantitative evaluation of randomized primary prevention trials employing cholesterol-lowering interventions, which indicate that such treatment is associated with a significant increase in deaths attributable to suicides, accidents and violence. Other preliminary evidence also suggests that serum lipid reduction may be associated with neurochemical and behavioral disturbances. Accordingly, the purposes of the proposed study are: (a) to determine whether or not cholesterol lowering is associated with changes in perceived health, well-being and neuropsychological functioning; and (b) to explore potential effects of cholesterol reduction on mood, behavior and neurochemical indices (e.g., CNS serotonergic activity) relating specifically to negative affect (aggression, depression) and impulsive behavior. We propose to conduct behavioral and neurochemical assessments, prior to and during treatment, in 300 hypercholesterolemic individuals randomly assigned to a potent cholesterol-lowering therapy (lovastatin) or placebo. An additional 100 participants having desirable (untreated) serum cholesterol levels will be evaluated similarly for purposes of comparison.
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