Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
Primary prevention trials which have shown that the lowering of serum cholesterol concentrations in middle-aged subjects by diet, drugs, or both leads to a decrease in coronary heart disease have also reported an increase in deaths due to suicide or violence. There has been no adequate explanation for this association. I have reviewed the relevant published work and describe a physiological mechanism that might account for this curious finding. One of the functions of serotonin in the central nervous system is the suppression of harmful behavioural impulses. When mouse brain synaptosomal membrane cholesterol is increased there is a pronounced increase in the number of serotonin receptors. Low membrane cholesterol decreases the number of serotonin receptors. Since membrane cholesterol exchanges freely with cholesterol in the surrounding medium, a lowered serum cholesterol concentration may contribute to a decrease in brain serotonin, with poorer suppression of aggressive behaviour.
The putative connection between low serum cholesterol and violence, including suicide, has spawned a large literature – one that I’m not wholly familiar with – so I can’t say how well the connection has held up. There are a number of papers disputing it, for example this one, which concludes that statin drugs do not result in mood changes. (Whether one can trust any research on statins is another question.)
Another paper, Cholesterol and violence: is there a connection?, found that
Observational studies (including cohort, case-control, and cross-sectional studies) consistently showed increased violent death and violent behaviors in persons with low cholesterol levels. Some meta-analyses of randomized trials found excess violent deaths in men without heart disease who were randomly assigned to receive cholesterol-lowering therapy. Experimental studies showed increased violent behaviors in monkeys assigned to low-cholesterol diets. Human and animal research indicates that low or lowered cholesterol levels may reduce central serotonin activity, which in turn is causally linked to violent behaviors. Many trials support a significant relation between low or lowered cholesterol levels and violence (P < 0.001). CONCLUSIONS: A significant association between low or lowered cholesterol levels and violence is found across many types of studies. Data on this association conform to Hill's criteria for a causal association. Concerns about increased risk for violent outcomes should figure in risk-benefit analyses for cholesterol screening and treatment.
By the way, the author of the first-linked paper above, Hyman Engelberg, was Marilyn Monroe’s personal physician.