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Relation between CYP2D6 phenotype and genotype and personality in healthy volunteers

Abstract:

Objectives: Our group has previously show that interindividual variability in CYP2D6 hydroxylation capacity was related to personality differences in cognitive social anxiety. Thus, we aimed to analyze whether this relationship between personality and CYP2D6 phenotype and genotype was found in a similar population of healthy volunteers from a different latitude and culture by using the same methodology. Methods: A total of 253 university students and staff from Havana Psychiatric Hospital and Calixto García Medical School in Cuba completed the Karolinska Scales of Personality (KSP), and were evaluated on debrisoquine hydroxylation capacity and CYP2D6 genotypes. KSP scores were compared between four groups, divided according to their CYP2D6 metabolic capacity: one of poor and three of extensive metabolizers. Furthermore, KSP scores were compared between another four different groups divided according to their number of CYP2D6 active genes: zero, one, two, and more than two. Results: In Cubans, the differences in cognitive social anxiety-related personality traits across the four CYP2D6 hydroxylation capacity groups were strikingly similar to those found in Spaniards. These differences also came out to be significant for psychic anxiety (p = 0.02) and socialization (p = 0.02). The same pattern of results obtained for the subscales of psychic anxiety, socialization, psychasthenia and inhibition of aggression with regard to phenotype in both the Cuban and Spanish studies were seen with regard to CYP2D6 genotypes. Conclusions: Corroborating these results further strengthens evidence of the relationship between CYP2D6 metabolic capacity and personality. In this population of healthy Cuban volunteers, the CYP2D6 hydroxylation oapacity was related to the degree of anxiety and socialization. These results support the postulated reduction of serotonin in CYP2D6 poor metabolizers, which may be associated with a cluster of behavioral traits (e.g., anxiety, impulsivity). Thus, research is warranted to determine CYP2D6 functional implications for interindividual differences in vulnerability to neuropsychiatric diseases and drug response. © 2008 Future Medicine Ltd.