CYP2D6 polymorphism in patients with eating disorders

Peñas-Lledó, Eva; Dorado, Pedro; Agüera, Zaida; Gratacòs, Mónica; Estivill, Xavier; Fernández‐Aranda, Fernando; LLerena, Adrián

doi:10.1038/tpj.2010.78

Cited by 24 publications

(10 citation statements)

References 19 publications

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“…Originally, an incidental observation in forensic studies aimed at evaluating the effect of poor metabolism on fatal intoxication; 151,152 this finding was replicated in two independent studies explicitly designed to test the association 153,154 and in further three independent databases of patients in treatment for depression 155,156 and eating disorders. 157 In the recent studies, the association is driven by a higher incidence and severity of suicidal behavior in the UM group. 155,156 Of possible significance to this association are data suggesting increased frequency of the CYP2D6 UM phenotype in depression more generally.…”

Section: Individual Differences In Behavior and Psychiatric Disordersmentioning

confidence: 98%

Genetic variability of drug-metabolizing enzymes: the dual impact on psychiatric therapy and regulation of brain function

2012

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Polymorphic drug-metabolizing enzymes (DMEs) are responsible for the metabolism of the majority of psychotropic drugs. By explaining a large portion of variability in individual drug metabolism, pharmacogenetics offers a diagnostic tool in the burgeoning era of personalized medicine. This review updates existing evidence on the influence of pharmacogenetic variants on drug exposure and discusses the rationale for genetic testing in the clinical context. Dose adjustments based on pharmacogenetic knowledge are the first step to translate pharmacogenetics into clinical practice. However, also clinical factors, such as the consequences on toxicity and therapeutic failure, must be considered to provide clinical recommendations and assess the cost-effectiveness of pharmacogenetic treatment strategies. DME polymorphisms are relevant not only for clinical pharmacology and practice but also for research in psychiatry and neuroscience. Several DMEs, above all the cytochrome P (CYP) enzymes, are expressed in the brain, where they may contribute to the local biochemical homeostasis. Of particular interest is the possibility of DMEs playing a physiological role through their action on endogenous substrates, which may underlie the reported associations between genetic polymorphisms and cognitive function, personality and vulnerability to mental disorders. Neuroimaging studies have recently presented evidence of an effect of the CYP2D6 polymorphism on basic brain function. This review summarizes evidence on the effect of DME polymorphisms on brain function that adds to the well-known effects of DME polymorphisms on pharmacokinetics in explaining the range of phenotypes that are relevant to psychiatric practice.

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Section: Individual Differences In Behavior and Psychiatric Disordersmentioning

confidence: 98%

Genetic variability of drug-metabolizing enzymes: the dual impact on psychiatric therapy and regulation of brain function

2012

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“…A high frequency of Ultra-rapid Metabolizers (UMs) has been previously described in Spanish population Peñas-Lledó et al, 2012). Given the Iberian Peninsula's influence on the hybrid population, we hypothesized that a high frequency of UMs would be present in the mestizo population.…”

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confidence: 99%

Ethnic background and CYP2D6 genetic polymorphisms in Costa Ricans

Céspedes-Garro

Jiménez-Arce

Naranjo

et al. 2014

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CYP2D6 differences have already been demonstrated within Latin American populations by the CEIBA.FP Consortium of the Ibero-American Network of Pharmacogenetics (RIBEF, as per the acronym in Spanish). However, within the population of Costa Rica, no research has been conducted until now, even though this population has a trihybrid component ancestry that represents an interesting condition. Thus, the present study was aimed to determine the frequency of Ultra-rapid Metabolizers (UMs) and Poor Metabolizers (PMs) in a Costa Rican population, as well as to determine whether there are differences in the CYP2D6-predicted phenotype frequencies among three Costa Rican groups with different ethnic backgrounds. Additionally, these frequencies of PMs and UMs obtained were compared with

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“…CYP2D6 has many polymorphisms associated with personality traits and neurologic or psychiatric disorders. A previous study showed that female CYP2D6 ultra-rapid metabolizers were more frequent among patients with eating disorders due to the alteration of brain serotonin concentration (Peñas-Lledó et al, 2012). This study indicated that enzymes capable of catalyzing the generation and elimination of endogenous compounds possibly regulate the local concentration and function of the endogenous compounds in the brain.…”

Section: Downloaded Frommentioning

confidence: 70%

Expression ofUDP-Glucuronosyltransferase 1(UGT1) and Glucuronidation Activity toward Endogenous Substances in HumanizedUGT1Mouse Brain

et al. 2015

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Although UDP-glucuronosyltransferases (UGTs) are important phase II drug-metabolizing enzymes, they are also involved in the metabolism of endogenous compounds. Certain substrates of UGTs, such as serotonin and estradiol, play important roles in the brain. However, the expression of UGTs in the human brain has not been fully clarified. Recently, humanized UGT1 mice (hUGT1 mice) in which the original Ugt1 locus was disrupted and replaced with the human UGT1 locus have been developed. In the present study, the expression pattern of UGT1As in brains from humans and hUGT1 mice was examined. We found that UGT1A1, 1A3, 1A6, and 1A10 were expressed in human brains. The expression pattern of UGT1As in hUGT1 mouse brains was similar to that in human brains. In addition, we examined the expression of UGT1A1 and 1A6 in the cerebellum, olfactory bulbs, midbrain, hippocampus, and cerebral cortex of hUGT1 mice. UGT1A1 in all brain regions and UGT1A6 in the cerebellum and cerebral cortex of 6-month-old hUGT1 mice were expressed at a significantly higher rate than those of 2-week-old hUGT1 mice. A difference in expression levels between brain regions was also observed. Brain microsomes exhibited glucuronidation activities toward estradiol and serotonin, with mean values of 0.13 and 5.17 pmol/min/mg, respectively. In conclusion, UGT1A1 and UGT1A6 might play an important role in function regulation of endogenous compounds in a regionand age-dependent manner. Humanized UGT1 mice might be useful to study the importance of brain UGTs in vivo.

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CYP2D6 polymorphism in patients with eating disorders

Cited by 24 publications

References 19 publications

Genetic variability of drug-metabolizing enzymes: the dual impact on psychiatric therapy and regulation of brain function

Genetic variability of drug-metabolizing enzymes: the dual impact on psychiatric therapy and regulation of brain function

Ethnic background and CYP2D6 genetic polymorphisms in Costa Ricans

Expression ofUDP-Glucuronosyltransferase 1(UGT1) and Glucuronidation Activity toward Endogenous Substances in HumanizedUGT1Mouse Brain

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