Cytochrome P450 2D6 Genotyping and Association with Tardive Dyskinesia in Chinese Schizophrenic Patients

Lam, Linda Chiu Wa; Garcia-Barceló, Mercè; Ungvari, Gabor S.; Tang, Wai Kwong; Lam, Vincent K. L.; Kwong, Stanley; Lau, Brandon; Kwong, Pearl; Waye, Mary Miu Yee; Chiu, Houn-Lin

doi:10.1055/s-2001-18035

Cited by 36 publications

(18 citation statements)

References 13 publications

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“…These results were similar to those of Ohmori et al [16] (p = 0.051) but inconsistent with those of Lam et al [17] (p = 0.65) In the findings of Lam et al [17], there was no significant difference in the allelic distribution between patients with or without TD. Although our results were similar to those of Ohmori et al [16], the interpretation might be different.…”

Section: Discussionsupporting

confidence: 61%

“…This finding was not consistent with the reports of Lam et al [17]. In their study, female patients with TD had significantly more frequently the homozygous TT genotype than female patients without TD.…”

Section: Discussioncontrasting

confidence: 56%

“…Ohmori et al [16] revealed a trend association between CYP2D6*10 genotypes and TD, and a significant correlation between genotypes and total Abnormal Involuntary Movement Scale (AIMS) scores. However, Lam et al [17] could not replicate this positive result, but found a significant increase in the frequency of the CYP2D6*10 allele in female TD patients. A recent study conducted by another Japanese group could not find a significant association between the CYP2D6*10 genotype and TD either [18].…”

Section: Introductionmentioning

confidence: 70%

“…Some differences may exist in patient recruitments and TD assessment, which may, in part, explain the inconsistent findings. Lam et al [17] enrolled patients who had been prescribed atypical antipsychotics in the TD and non-TD groups and defined TD as the presence of a 'minimal' score on 2 or more body regions, or a 'mild' or severer score on any one region. We recruited patients who were only treated with typical antipsychotics in both the TD and non-TD group, and only included persistent TD defined as having abnormal, involuntary movements being 'mild' on 2 or more areas of the body, or 'moderate' on 1 or more areas according to the RDC [19].…”

Section: Discussionmentioning

confidence: 99%

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Cytochrome P-450 2D6*10 C188T Polymorphism Is Associated with Antipsychotic-Induced Persistent Tardive Dyskinesia in Chinese Schizophrenic Patients

et al. 2004

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Typical antipsychotic treatment had been postulated to be a risk factor for the susceptibility to tardive dyskinesia (TD). The cytochrome P-450 debrisoquine/sparteine hydroxylase (CYP2D6) metabolizes a majority of antipsychotics and exhibits various phenotypes on enzymatic activities from poor metabolizers to ultrarapid metabolizers. The various phenotypes are encoded by polymorphic genetic variants on the CYP2D6 gene. Although several studies had explored the association between the CYP2D6*10 C188T polymorphism, which encodes the phenotype intermediate metabolizers, and TD in Orientals, the findings were inconclusive. In the present study, we examined the relationship between the CYP2D6*10 C188T polymorphism and the TD occurrence in 216 Chinese schizophrenic patients (113 patients with TD and 103 patients without TD) and explored the correlation between the TD severity assessed by the Abnormal Involuntary Movement Scale (AIMS) and each C188T genotype in the 113 TD patients. Using logistic regression analysis, we found a modest association (p = 0.045) between TD and C188T genotypes. This positive finding was only observed in male patients (p = 0.001), but not in females. Our findings also support the correlation between AIMS scores and C188T polymorphism within the TD group after adjusting for confounding effects with the multiple regression analysis (p = 0.033). We concluded that the CYP2D6*10 C188T polymorphism may be associated with the susceptibility to the occurrence of TD induced by typical antipsychotics, especially in male patients, and may also be correlated with AIMS scores in TD patients.

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Section: Discussionsupporting

confidence: 61%

Section: Discussioncontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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Cytochrome P-450 2D6*10 C188T Polymorphism Is Associated with Antipsychotic-Induced Persistent Tardive Dyskinesia in Chinese Schizophrenic Patients

et al. 2004

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“…Our findings differ from those of Lam et al, 27 who reported that only female CYP2D6*10B homozygotes showed an association with TD, although the sample size was relatively small. In this Korean cohort, the females' odds ratio estimates do not support an association between CYP2D6 variant genotypes and TD; however, due to the small number of women in this cohort, these estimates are probably unreliable (Table 5).…”

Section: Discussioncontrasting

confidence: 56%

Association between CYP2D6 genotype and tardive dyskinesia in Korean schizophrenics

Nikoloff

Fairchild

et al. 2002

Pharmacogenomics J

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The CYP2D6 gene codes for human cytochrome P450 2D6 enzyme, which is responsible for the metabolism of many psychiatric drugs. In schizophrenic patients treated with neuroleptics, decreased or loss of function CYP2D6 alleles may contribute to the development of tardive dyskinesia (TD), a movement disorder that frequently occurs with chronic neuroleptic treatment. The goal of this study was to determine whether the occurrence of TD is associated with CYP2D6 genotype in a cohort of Korean schizophrenics by employing a CYP450 GeneChip s oligonucleotide microarray and PCR assays to screen for 19 CYP2D6 alleles. Our results revealed that males with at least one decreased or loss of function allele have a moderately greater chance of developing TD than males with only wild-type alleles. Female schizophrenics did not have a significantly greater chance of developing TD. Our results demonstrate the utility of CYP2D6 microarrays to assess genotype status in this Korean cohort.

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Tardive Dyskinesia

Lehosit

Pirmohamed

Vijayakumar

et al. 2015

Encyclopedia of Life Sciences

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Tardive syndromes (TS) are a group of related iatrogenic disorders characterised by persistent abnormal involuntary movements resulting from the use of dopamine receptor blocking medications, which are often used to treat psychiatric and gastrointestinal conditions. The most common of the TS is classic tardive dyskinesia, characterised by involuntary stereotypic movements in the mouth region such as lip smacking or pursing, chewing, facial grimacing and tongue movements. TS can be highly disabling, difficult to treat and have the potential to be permanent, making their prevention of paramount importance. The pathophysiological basis of the TS is poorly understood. Treatment options include oral medications, botulinum toxin injections and deep brain stimulation surgery. More research is needed to determine the best available treatment options and to identify new treatments. Key Concepts Tardive syndromes are a group of related iatrogenic disorders characterised by persistent abnormal involuntary movements. They result from the long‐term use of dopamine receptor blocking medications, which are often used in the treatment of psychiatric and gastroenterological conditions. Tardive syndromes can persist after discontinuation of the causative drug and have the potential to be permanent. There are various forms of tardive syndromes, the most common of which is classic tardive dyskinesia, described as repetitive, rhythmic, involuntary movements that are typically present in the mouth region. Elderly individuals, women, diabetics and non‐whites appear to be most vulnerable to the development of tardive dyskinesia. Treatment options for tardive syndromes are limited, and more research is needed to determine the best available treatment strategies and to identify potential new therapies.

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Cytochrome P450 2D6 Genotyping and Association with Tardive Dyskinesia in Chinese Schizophrenic Patients

Abstract: The sex differences in CYP 2D6 genotyping and vulnerability to develop TD suggest that a biological predisposition that affects pharmacokinetics may be more significant in women, whereas other factors may be more important in men.

Cited by 36 publications

References 13 publications

Cytochrome P-450 2D6*10 C188T Polymorphism Is Associated with Antipsychotic-Induced Persistent Tardive Dyskinesia in Chinese Schizophrenic Patients

Cytochrome P-450 2D6*10 C188T Polymorphism Is Associated with Antipsychotic-Induced Persistent Tardive Dyskinesia in Chinese Schizophrenic Patients

Association between CYP2D6 genotype and tardive dyskinesia in Korean schizophrenics

Tardive Dyskinesia

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