By the early 1990s, the link between high cholesterol and heart disease was well established and the era of therapies to lower cholesterol with the intent of reducing heart disease risk had begun. In this decade, hundreds of studies and tens of thousands of patients were enrolled in various trials which showed that lowering cholesterol both through lifestyle changes and pharmacologic means was beneficial. However, some scientists wondered if there was a hidden price to be had for better heart health. In 1990, a study reviewing several of these cholesterol lowering trials concluded that lowering cholesterol did lower heart disease risk, but surprisingly increased the risk of death from accidents, suicide, and violence. Was lowering cholesterol adversely affecting behavior?
It would not be that hard to believe that cholesterol levels can affect behavior. After all, the brain is the most cholesterol-rich organ in our bodies, containing ~25% of our total body cholesterol despite the fact that is only 2% of our total body weight. Furthermore, cholesterol is a vital ingredient in many normal brain cell functions such as maintaining cell membrane integrity and the processing/handling of brain neurotransmitters - the regulatory chemicals of the brain. One neurotransmitter in particular called serotonin is quite involved in the regulation of mood. Low serotonin levels have been linked to depression and medications called serotonin reuptake inhibitors (SSRIs) such as Prozac improve mood by increasing brain serotonin levels. Both animal and human studies have shown that low cholesterol diets seem to decrease serotonin levels. One key question that still remains unanswered is how does serum cholesterol affect brain cholesterol since the brain makes and regulates its own cholesterol independent of serum cholesterol. Other evidence showing a cholesterol and behavior link comes from autopsy studies of people with mental illness such as schizophrenia, major depression, and bipolar disorder. Cholesterol content in the brains of these individuals was found to be lower when compared to normal behavior controls.
Behaviors such as depressed mood, aggression, suicide, and impulsivity have all been potentially linked to low cholesterol. Of these, depression has been the most studied. Although some studies of low cholesterol and negative mood have not shown a positive correlation, there are many studies that do. In these positive studies, low HDL in women may be more of a factor than high LDL and total cholesterol which is more of a risk factor in men. Older women may be more susceptible as well. Suicide risk may be mildly increased especially in young women with low HDL, but the evidence is mixed. Evidence to suggest a link between aggression, specifically physical violence, and low cholesterol are in general more consistently positive. A study looking at monkeys on a low cholesterol diet showed that as serum cholesterol fell, physically aggressive behavior increased. A human study then looked at the total cholesterol and LDL levels of men with violent criminal records which included crimes such as homicide, rape, and arson. When compared with men with no criminal record, the total cholesterol and LDL levels of the men with violent criminal records were much lower. One interesting hypothesis to explain this increase in violence with lower cholesterol has to do with our primordial instinct and evolutionary natural selection. During periods of abundant food, cholesterol and serotonin levels are high. Passive and non-aggressive behavior predominates. However, when food is scarce, cholesterol and serotonin levels fall. More physically aggressive behavior predominates which may be helpful when hunting for food.