Cholesterol, violent death, and mental disorder
BMJ 1994; 309 doi: https://doi.org/10.1136/bmj.309.6952.421 (Published 13 August 1994) Cite this as: BMJ 1994;309:421
- A Ryman
Although primary prevention studies have shown that reducing serum cholesterol concentration leads to a clear reduction in cardiac morbidity and mortality, total mortality is unaffected. The increase in deaths from accidents, violence, and suicide in the treated groups has not yet been adequately explained,1 though an association between low cholesterol concentration and psychiatric illness has been suggested as a possible cause.2 The finding has also been elaborated in neurobiological terms, implicating a relation between membrane cholesterol, serotonin, and impulsivity.3
How seriously should this association be taken? Is the apparent relation of suicidal, accidental, and violent death with low serum cholesterol concentrations a true finding or simply due to chance? The association was initially regarded as an anomalous occurrence, but it has been too consistent to be dismissed.4 It has appeared in studies irrespective of whether drugs or diet were used to lower cholesterol concentrations. A study to examine the relation between cholesterol concentration and short term mortality from injury confirmed an inverse association in men.5 A more recent study, published in this issue (p 445),6 failed to replicate this finding in relation to death due to accidents and violence, but it used a relatively high cut off for a “low” cholesterol value. In a population with naturally low cholesterol concentrations (Shanghai, China) a low cholesterol concentration was significantly associated with a higher death rate from non-medical causes.7 The findings are therefore unlikely to be due simply to chance. Furthermore, these studies support an association with low serum cholesterol concentration itself, in addition to a treatment effect.
Possible causes
Why should there be this association? A recent review of cholesterol values and mortality showed a pronounced difference between studies of employed men, presumed to be healthy at recruitment, and community studies2: the employed cohorts showed no excess mortality. In the community cohorts the excess mortality was explained by disease, or factors that cause disease, lowering cholesterol concentrations in a proportion of the cohorts. Depression is the main psychiatric illness that predisposes to suicide and could itself cause low cholesterol concentrations through poor diet and weight loss. This explanation would, however, require that there was a chance assignment of a higher proportion of subjects with psychiatric disorder to the intervention groups than to the control groups in all the studies, which seems unlikely. It seems equally feasible that the lowering of cholesterol concentrations caused an increase in deaths only in a population more vulnerable to psychiatric disorder and that employed cohorts are protected from this effect. There is certainly evidence that unemployment predisposes to parasuicide and psychiatric morbidity.8
Need to include mood ratings
Our current understanding of the relation between cholesterol metabolism and psychiatric illness is poor. Studies have examined the relation between low serum cholesterol values and psychiatric disorder. Virrkunen found an inverse association between cholesterol concentrations and antisocial personality,9 but others have found no link with aggressive personality traits10 or minor psychiatric disorder as defined by the general health questionnaire.11 Studies of cholesterol concentrations among older men with depressive symptoms showed an inverse relation,12,13 although in one study significance was lost after correction for weight loss. This supports an association between low serum cholesterol values and depressive illness but does not establish the direction of causality.
More detailed investigation will be required to elucidate the relation between cholesterol, mortality, and psychiatric illness. So far no studies have examined the effect of lowering cholesterol concentrations on mental state. Any further primary prevention studies to assess psychiatric morbidity due to low or lowered cholesterol concentrations should therefore include ratings of mood. The contribution of low cholesterol concentrations to suicide should also be addressed in more severe psychiatric illness, since as many as 10-15% of patients with schizophrenia or manic depression die by suicide.14 Predicting the risk of suicide in psychiatrically ill patients is notoriously difficult. The possibility that a low or falling cholesterol concentration is a marker of risk merits further study. It may also contribute to an increased understanding of the underlying biochemistry and neuropharmacology of psychiatric disorder and suicide.