To the Editor: We read with much interest the article by Antti Tanskanen, M.D., Ph.D., et al. (1), which demonstrated the positive relationship of high serum total cholesterol levels to greater risk of violent suicide. This report went on to suggest an association between high total cholesterol level and depression (by means of a correlation of both high total cholesterol level and depression with low omega-3 polyunsaturated fatty acids). We argue that the link with high total cholesterol level and depression is unlikely to be exclusive. First, Dr. Tanskanen et al. (1) found no association between high total cholesterol level and risk of nonviolent suicide. Because suicides associated with depression include both violent and nonviolent ones, the hypothesis of a direct association between high total cholesterol level and depression is unlikely.

Second, Partonen et al. (2)demonstrated that a low total cholesterol level was associated with depressed mood and subsequently a high risk of hospital treatment because of major depressive disorder and death from suicide in a large sample of men. Also, Terao et al. (3) found the greatest number of depressive states in the subject group with the lowest cholesterol levels (<158 mg/dl), although peaks in numbers of depressive states were seen throughout the range of stratified cholesterol levels.

Neuroendocrine studies (4, 5) complicate the picture, as both subjects with total cholesterol levels less than 150 mg/dl (4) and with low levels of high-density lipoprotein cholesterol (5) had significantly blunted cortisol responses to an m-CPP challenge (which could be associated with reduced serotonergic function and depressive states). Buydens-Branchey et al. (5) found an association between low high-density lipoprotein level and a history of aggression, which is possibly consistent with the argument of Dr. Tanskanen et al.

We conclude that a high level of total cholesterol is not exclusively linked to depressive disorders, but the overall picture is complicated. As Dr. Tanskanen et al. (1) found, depressed subjects with high cholesterol levels may be at a greater vulnerability to violent suicide, but the reasons for this are unclear.