SPECIAL SECTION: LETTER TO THE EDITOR
Statins to reduce risk of depression
Barbara Wirleitner, PhD,
Barbara Sperner-Unterweger, MD and
Dietmar Fuchs, PhD
Institute of Medical Chemistry and Biochemistry, Department of Psychiatry, University of Innsbruck, Ludwig Boltzmann Institute of AIDS Research, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria
dietmar.fuchs{at}uibk.ac.at
We read with great interest the findings by Young-Xu and co-workers on long-term use of statins to reduce the risk of depression (1). Patients treated with statins had a lower incidence of abnormal psychological scores. A 30% to 40% risk reduction for depression was found in this group. At first glance, the effect of statins appears to relate to cholesterol reduction. However, in addition to inhibition of HMG-CoA reductase, certain statins were found to suppress the Th1-type cytokines interferon-gamma (IFN- ) and interleukins (IL)-2 and -12, while promoting secretion of Th-2 cytokines IL-4, IL-5, and IL-10 (2). Such data favorably compare to results we have generated in vitro on atorvastatin to suppress IFN--mediated biochemical events in peripheral blood mononuclear cells and in monocytes (3). Atorvastatin was shown to diminish in a dose-dependent manner activity of indoleamine (2,3)-dioxygenase (IDO). Enzyme IDO is inducible by IFN- and degrades the essential amino acid tryptophan via the kynurenine pathway. Therefore, accelerated tryptophan degradation by IDO activation is commonly observed in a broad range of diseases associated with endogenous formation of Th1-type cytokine IFN- (4), including patients with coronary heart disease (CHD) (5).
Because tryptophan is precursor of neurotransmitter 5-hydroxytryptamine (serotonin), lowered tryptophan availability increases the susceptibility of depression in patients (4); for example, in patients with colorectal cancer an association was reported between lowered serum tryptophan related to immune activation and impaired quality of life (6). Thus, when statins are able to block IDO and thereby increase tryptophan concentrations, it is reasonable that statins would reduce the risk of depression in CHD patients with an accelerated tryptophan degradation (5). Whether statins improve tryptophan metabolism in patients is worth being tested in clinical trials.
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1. Young-Xu Y, Chan KA, Liao JK, Ravid S, Blatt CM. Long-term statin use and psychological well-being. J Am Coll Cardiol. 2003;42:690–697[Abstract/Free Full Text]
2. Youssef S, Stuve O, Patarroyo JC, et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature. 2002;420:78–84[CrossRef][Medline]
3. Neurauter G, Wirleitner B, Laich A, Schennach H, Weiss G, Fuchs D. Atorvastatin suppresses interferon--induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines. Clin Exp Immunol. 2003;131:264–267[CrossRef][Medline]
4. Widner B, Laich A, Sperner-Unterweger B, Ledochowski M, Fuchs D. Neopterin production, tryptophan degradation and mental depression: what is the link? Brain Behav Imm. 2002;16:590–595[CrossRef][Medline]
5. Wirleitner B, Rudzite V, Neurauter G, et al. Immune activation and degradation of tryptophan in coronary heart disease. Eur J Clin Invest. 2003;33:550–554[CrossRef][Medline]
6. Huang A, Fuchs D, Widner B, Glover C, Henderson DC, Allen-Mersh TG. Serum tryptophan decrease correlates with immune activation and impaired quality of life in colorectal cancer. Br J Cancer. 2002;86:1691–1696[CrossRef][Medline]
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