Introduction: 5-methoxytryptamine (5-MT), a precursor of serotonin, is considered to be an endogeous substrate of cytochrome P450 2D6 (CYP2D6). Homozygous carriers of the variant allele CYP2D6*4 lack CYP2D6 emzyme activity. Relative to extensive metabolizers, these poor metabolizers may have lower baseline serotonin concentrations in various brain regions, and may be more prone to depression or anxity. Aim: To test whether the CYP2D6*4/*4 genotype is associated with a predisposition to depression or anxiety disorders in the elderly. Materials & methods: We conducted a cross-sectional study within the Rotterdam Study, a population-based cohort study, among persons aged 55 years or older, who were screened for depression and anxiety disorder at two consecutive examination rounds. Logistic regression was used to analyze the association between the CYP2D6*4 polymorhism and the risk of depression or anxiety disorders. Results: The risk of major depression in CYP2D*64/*4 was not significantly different from extensive metabolizers (OR = 0.85; 95% Cl: 0.36-2.00; p = 0.72). Neither did we find an association between CYP2D6 genotype and minor depression (OR = 1.56; 95% Cl: 0.69-3.52; p = 0.28). No increased risk of anxiety disorders was found (OR = 1.19; 95% Cl: 0.68-2.09; p = 0.55). Conclusion: Variation in the CYP2D6 gene is not related to a predisposition or anxiety disorders in the elderly.

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Keywords 5-Methoxytryptamine, Anxiety, CYP2D6, Depression, Serotonin
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Journal Pharmacogenomics
Bijl, M.J, Luijendijk, H.J, van den Berg, J.F, Visser, L.E, van Schaik, R.H.N, Hofman, A, … Stricker, B.H.Ch. (2009). Association between the CYP2D6*4 polymorphism and depression or anxiety in the elderly. Pharmacogenomics, 10(4), 541–547. doi:10.2217/pgs.09.9