In their recent article,1 Santiago and Dalen focus on the intriguing relationship between low cholesterol levels and violence. They note that Muldoon and colleagues2 suggested that lowering the cholesterol level might trigger behavioral, affective, or nervous system changes, and they, additionally, proposed the use of serotonin as an intermediary. Supporting evidence for this neurotransmitter, however, is meager, which is not surprising as serotonin is more associated with suicide related to depression than with violence.
However, the latter is suggestive of increased sympathoadrenal activity, for which there is evidence. As cholesterol is essential for steroid production, reduced availability should result in a negative feedback response involving its tropic hormone, adrenocorticotropin, for which supporting statistics exist.2 Furthermore, in amphibians, cholesterol itself has been shown to downregulate hypothalamo-pituitary-adrenal activity,3 establishing at least a regulatory role in vertebrates.
Finally, a more basic point. Survival requires that a falling level of