Individuals at risk for coronary artery disease are often prescribed statins, which are medications that reduce the amount of cholesterol in the blood. By lowering cholesterol levels, these individuals have a lower incidence of heart disease, heart attacks, and stroke. Simvastatin and pravastatin are two common statins that are often prescribed for individuals with high cholesterol. While statins are effective at lowering cholesterol levels, their effect on mood, behavior, and aggression has not been widely studied. Preliminary research has shown that lowering cholesterol levels may lead to an increase in aggressive behaviors and a change in cognitive function. Serotonin, a type of neurotransmitter, is believed to play an important role in the regulation of mood, as well as behavior and cognition. The direct effect of statins on serotonin levels remains unknown. The purpose of this study is to evaluate the effect of simvastatin and pravastatin on mood, cognition, aggression, and serotonin levels.

This study will enroll individuals who do not currently take cholesterol-lowering medications. Participants will be randomly assigned to receive 20 mg of simvastatin, 40 mg of pravastatin, or placebo for 6 months. Study visits will occur at baseline and Months 1, 3, 6, and 8. Height, weight, and waist circumference will be measured at all study visits. Blood and urine will be collected for laboratory testing, and standardized psychological questionnaires will assess cognition, aggression, mental flexibility, memory, depression, sleep quality, and quality of life at Months 1, 6, and 8. At Month 3, medication side effects will be monitored and a liver function test will be performed. Participants’ partners will take part in a telephone interview at this time. At baseline and Month 6, some participants will undergo cardiac reactivity testing. During this procedure, participants will be videotaped and monitored for vital sign changes (blood pressure and heart rate) while they talk about potentially stressful situations.

Inclusion Criteria:

• LDL cholesterol level between 115-190 mg/dL

• Able to fast prior to blood draw

• Able to comfortably read and write in English

• Able and willing to refrain from donating whole blood during study participation

• Willing to abstain from consuming large amounts of grapefruit juice

Exclusion Criteria:

• Current use of lipid-lowering medications

• Symptomatic atherosclerotic disease, such as coronary artery disease, kidney failure or insufficiency, peripheral arterial disease, or cerebrovascular disease

• Cancer

• HIV infected

• Medical or psychiatric condition that prevents full study participation or follow-up (e.g., active psychosis)

• Active liver disease or unexplained persistent elevated transaminase levels

• Major surgery or hospitalization in the 3 months prior to study entry

• Current use of cyclosporin, erythromycin, clarithromycin, nefazodone, or any “azole” antifungals, including fluconazole, itraconazole, ketoconazole, mibefradil, or protease inhibitors

• Female of childbearing potential

• Current participation in another clinical trial