Association between the CYP2D6*4 polymorphism and depression or anxiety in the elderly.
BACKGROUND
5-methoxytryptamine (5-MT), a precursor of serotonin, is considered to be an endogenous substrate of cytochrome P450 2D6 (CYP2D6). Homozygous carriers of the variant allele CYP2D6*4 lack CYP2D6 enzyme 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 anxiety.


OBJECTIVE
To test whether the CYP2D6*4/*4 genotype is associated with a predisposition to depression or anxiety disorders in the elderly.


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 disorders at two consecutive examination rounds. Logistic regression was used to analyze the association between the CYP2D6*4 polymorphism and the risk of depression or anxiety disorders.


RESULTS
The risk of major depression in CYP2D6*4/*4 was not significantly different from extensive metabolizers (OR = 0.85; 95% CI: 0.36-2.00; p = 0.72). Neither did we find an association between CYP2D6 genotype and minor depression (OR = 1.56; 95% CI: 0.69-3.52; p = 0.28). No increased risk of anxiety disorders was found (OR = 1.19; 95% CI: 0.68-2.09; p = 0.55).


CONCLUSIONS
Variation in the CYP2D6 gene is not related to a predisposition to depression or anxiety disorders in the elderly.
Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Monique J
MJ
Bijl
Hendrika J
HJ
Luijendijk
Julia F
JF
van den Berg
Loes E
LE
Visser
Ron H N
RH
van Schaik
Albert
A
Hofman
Arnold G
AG
Vulto
Teun
T
van Gelder
Henning
H
Tiemeier
Bruno H Ch
BH
Stricker
D000368:Aged; D000375:Aging / Q000235:genetics*; D001008:Anxiety Disorders / Q000201:enzymology / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003863:Depression / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D011110:Polymorphism, Genetic
D019389:Cytochrome P-450 CYP2D6