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We are pleased that Dr. Wirleitner and colleagues found our report (1)of interest. We would like to point out that in our study the effects of statins on psychological well-being appeared to be independent of both cholesterol reduction and baseline cholesterol level. Because the effects of statins on the psychological well-being of our patients were related to the lipophilicity of the statin and not to the level of cholesterol reduction, we postulate that the biological effect may be mediated by statin's direct effect on the central nervous system. By inhibiting HMG-CoA reductase in neuronal cells, statins could potentially alter cellular cholesterol content and lipid membrane rafts. This could lead to changes in neuronal function as manifested in psychological well-being. Another consequence of HMG-CoA reductase inhibition is inhibition of signaling molecules that depend upon isoprenylation for proper function. In this respect, statins could alter the balance of Th1/Th2 cell population, leading to potential blockade of indoleamine dioxygenase. Indeed, statins have been shown to decrease Th1-mediated inflammatory response in an autoimmune mouse model of multiple sclerosis (2). This effect was observed without significant changes in serum cholesterol levels. Thus, it is possible that the “antidepressant” effect of statins in our patient population could be mediated by a cholesterol-independent immunomodulatory effect of statins.
We are encouraged by Dr. Wirleitner and colleagues' letter, which supports our clinical observation by providing another clue to a potential biological mechanism. We do agree with them that it should be tested in clinical trials whether statins improve tryptophan metabolism, as that would provide data to support or refute the proposed biological mechanism.
- American College of Cardiology Foundation