Pharmacopsychiatry 2001; 34(6): 238-241
DOI: 10.1055/s-2001-18035
Original Paper
© Georg Thieme Verlag Stuttgart · New York

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

L. C. W. Lam, M. M. Garcia-Barcelo, G. S. Ungvari, W. K. Tang, V. K. L. Lam, S. L. Kwong, B. S. T. Lau, P. P. K. Kwong, M. M. Y. Waye, H. F. K. Chiu
  • Departments of Psychiatry (LCWL, MMGB, GSU, WKT, HFKC) and Biochemistry (MMYW), the Chinese University of Hong Kong, Kwai Chung Hospital (SLK, PPKK) and Lai Chi Kok Hospital (BSTL), Hong Kong
Further Information

Publication History

Publication Date:
26 October 2001 (online)

Background: The discovery of Cytochrome P450 2D6 (CYP 2D6) polymorphism is implicated in individual differences in drug metabolism rate. Mutation with defective alleles is associated with reduced metabolism of many anti-psychotic drugs metabolized by CYP 2D6. This may contribute to the development of tardive dyskinesia (TD) in patients with prolonged exposure to anti-psychotic drugs. Methods: In this controlled study, the genotype of CYP 2D6*10 alleles, movement disorders and clinical characteristics in 38 Chinese schizophrenic patients with TD were compared with 38 age- and sex-matched schizophrenia patients without TD. Results: There was no significant correlation between CYP 2D6*10 genotypes and TD in men. However, a significant increase in the frequency of CYP 2D6*10 allele was found in female patients with TD. Conclusions: 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.

1 The work was supported by the Direct Grant for Research of the Chinese University of Hong Kong (Project Code: 2040708).


  • 1 American Psychiatric Association. Diagnostic Criteria for DSM-IV. Washington; 1994
  • 2 Andreassen O A, MacEwan T, Gulbrandsen A K, McCreadie R G, Steen V M. Non-functional CYP2D6 alleles and risk for neuroleptic-induced movement disorders in schizophrenic patients.  Psychopharmacology (Berl). 1997;  131 174-179
  • 3 Armstrong M, Daly A K, Blennerhasett R, Ferrier N, Idle J R. Antipsychotic drug-induced movement disorders in schizophrenics in relation to CYP2D6 genotype.  Br J Psychiatry. 1997;  170 23-26
  • 4 Arthur H, Dahl M L, Siwers B, Sjoqvist F. Polymorphic drug metabolism in schizophrenic patients with tardive dyskinesia.  J Clin Psychopharmacology. 1995;  15 211-216
  • 5 Barnes T RE. A rating scale for drug-induced akathisia.  Br J Psychiatry. 1988;  154 672-676
  • 6 Bertilsson L, Lou Y Q, Du Y L, Liu Y, Kuang T Y, Liao X M, et al. Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquin and S-mephenytoin.  Clin Pharmacol Ther. 1992;  51 388-397
  • 7 Bertilsson L. Geographical/Interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19.  Clin Pharmacokinet. 1995;  29 192-209
  • 8 Chiu H FK, Shum P, Lau J, Lam L, Lee S. Prevalence of tardive dyskinesia, tardive dystonia and respiratory dyskinesia in Chinese psychiatric patients in Hong Kong.  Am J Psychiatry. 1992;  149 1081-1085
  • 9 Garcia-Barcelo M, Chow L Y, Chiu H F, Wing Y K, Lee D TS, Lam K L, et al. Genetic analysis of the CYP2D6 locus in a Hong Kong Chinese population.  Clin Chem. 2000;  46 18-23
  • 10 Gough A C, Miles J S, Spurr N K, et al. Identification of the primary gene defect at cytochrome P450 CYP2D locus.  Nature. 1990;  347 773-776
  • 11 Guy W. ECDEU Assessment for Psychopharmacology. Washington, DC; HEW Public Health Service 1976: 534-537
  • 12 Johansson I, Lundqvist E, Bertilsson L, Dahl M L, Sjoqvist F, Ingelman-Sunderberg M, et al. Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine.  Proc Natl Acad Sci USA. 1993;  90 11825-11829
  • 13 Johansson I, Oscarson M, Yue Q Y, Bertilsson L, Sjöqvist F, Ingelman-Sundberg M. Genetic analysis of the Chinese cytochrome P4502D locus: characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation.  Mol Pharmacol. 1994;  46 452-259
  • 14 Kapitany T, Meszaros K, Lenzinger E, Schindler S D, Barnas C, Fuchs K, et al. Genetic polymorphismus for drug metabolism (CYP 2D6) and tardive dyskinesia in schizophrenia.  Schizophrenia Res. 1998;  32 101-106
  • 15 Lin K M, Poland R E, Wan Y J, Smith M W, Lesser I M. The evolving science of pharmacogenetics: clinical and ethnic perspectives.  Psychopharmacol Bull. 1996;  32 205-217
  • 16 Mihara K, Suzuki A, Kondo T, Yasui N, Furukori H, Nagashima U, et al. Effects of the CYP2D6*10 allele on the steady-state plasma concentrations of haloperidol and reduced haloperidol in Japanese patients with schizophrenia.  Clin Pharmacol Ther. 1999;  65 291-294
  • 17 Munitz M-R, Benjamin S. How to examine patients using the Abnormal Involuntary Movement Scale.  Hosp Com Psychiatry. 1988;  39 1172-1177
  • 18 Muscettola G, Barbato G, Pampallona S, Casiello M, Bollini P. Extrapyramidal syndromes in neuroleptic-treated patients: prevalence, risk factors, and association with tardive dyskinesia.  J Clin Psychopharmacol. 1999;  19 203-208
  • 19 Ohmori O, Suzuki T, Kojima H, Shinakai T, Terao T, Mita T, et al. Tardive dyskinesia and debrisoquine-4-hydroxylase (CYP 2D6) genotype in Japanese schizophrenics.  Schizophrenia Res. 1998;  32 107-113
  • 20 Overall J E, Gorham D R. The Brief Psychiatric Rating Scale.  Psychological Rep. 1962;  10 799-812
  • 21 Schooler N R, Kane J M. Research diagnoses for tardive dyskinesia.  Arch Gen Psychiatry. 1982;  39 486-487
  • 22 Simpson G M, Angus J WS. A rating sclae for extrapyramidal side effects.  Acta Psychiat Scandinavica (Suppl). 1970;  45 11-19
  • 23 Someya T, Suzuki Y, Shimoda K, Hirokane G, Morita S, Yokono A, et al. The effect of cytochrome P450 2D6 genotypes on haloperidol metabolism: a preliminary study in a psychiatric population.  Psychiatry Clin Neurosc. 1999;  53 593-597
  • 24 Statistical Package for Social Sciences SPSS 9.0. Chicago, USA; SPSS Inc. 1999
  • 25 Suzuki A, Otani K, Mihara K, Yasui N, Kanebo S, Inoue Y, et al. Effects of the CYP 2D6 genotype on the steady-state plasma concentrations of haloperidol and reduced haloperidol in Japanese schizophrenic patients.  Pharmacogenetics. 1997;  7 415-418
  • 26 Van Os J, Fahy T, Jones P, Harvey I, Toone B, Murray R. Tardive dyskinesia: who is at risk?.  Acta Psychiatr Scand. 1997;  96 206-216
  • 27 Wang S L, Huang J D, Lai M D, Liu B H, Lai M L. Molecular basis of genetic variation in debrisoquine hydroxylation in Chinese subjects: polymorphism in RFLP and DNA sequence of CYP2D6.  Clin Pharmacol Ther. 1993;  53 410-418
  • 28 Wang S L, Lai D M, Lai M L, Huang J D. R296C and other CY2D6 mutations in Chinese.  Pharmacogenetics. 1995;  5 385-388
  • 29 Wang S L, Lai M D, Huang J D. G169R mutation diminishes the metabolic activity of Cyp 2D6 in Chinese.  Drug Metab Dispos. 1999;  27 385-388
  • 30 Woerner M G, Alvir J M, Saltz B L, Lieberman J A, Kane J M. Prospective study of tardive dyskinesia in the elderly: rates and risk factors.  Am J Psychiatry. 1998;  155 1521-1528
  • 31 Woerner M G, Mannuzza S, Kane J M. Anchoring the BPRS: an aid to improve reliability.  Psychopharmacol Bulletin. 1998;  24 112-117
  • 32 Xie H G, Xu Z H, Luo X, Huang S L, Zeng F D, Zhou H H. Genetic polymorphisms of debrisoquine and S-mephenytoin oxidation metabolism in Chinese populations: a meta-analysis.  Pharmacogenetics. 1996;  6 235-238

1 The work was supported by the Direct Grant for Research of the Chinese University of Hong Kong (Project Code: 2040708).

Linda C. W. LamM.D. 

Department of Psychiatry
The Chinese University of Hong Kong

Shatin, N.T.
Hong Kong, PRC

Phone: + 852-2646-2284

Fax: + 852-2632-3630