Hostname: page-component-848d4c4894-nmvwc Total loading time: 0 Render date: 2024-06-17T04:05:50.985Z Has data issue: false hasContentIssue false

Tardive dyskinesia is not associated with the polymorphisms of 5-HT2A receptor gene, serotonin transporter gene and catechol-o-methyltransferase gene

Published online by Cambridge University Press:  16 April 2020

Hasan Herken*
Department of Psychiatry, Medical Faculty of Gaziantep University, Gaziantep City, Turkey
M. Emin Erdal
Samsun Mental Hospital, Turkey
Ömer Böke
Department of Medical Biology and Genetics, Medical Facultyof Mersin University, Turkey
Haluk A. Savaş
Department of Psychiatry, Medical Faculty of Gaziantep University, Gaziantep City, Turkey
*E-mail address:
Get access



The pathophysiology of tardive dyskinesia (TD) is not completely understood.


To assess the relationship of TD with 5-HT2A receptor gene, serotonin transporter gene (5 HTT), and catechol-o-methyltransferase (COMT) gene polymorphisms.


Our study comprised 111 unrelated subjects who strictly met DSM-IV criteria for schizophrenia and 32 TD, and 79 healthy unrelated controls; all the subjects were of Turkish origin. The analyses of 5-HT2A receptor gene, 5 HTT gene, and COMT gene polymorphisms were performed using polymerase chain reaction (PCR) technique.


The polymorphisms of these genes were not significantly different between the schizophrenic patients, TD and control subjects.


Our findings indicated that 5-HT2A receptor gene, 5 HTT gene, and COMT gene polymorphisms were similar in schizophrenia with non-TD, schizophrenia with TD, and healthy controls. These polymorphisms, though, do not help to evaluate the susceptibility to TD.

Original article
Copyright © Éditions scientifiques et médicales Elsevier SAS 2002

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


This study was partly presented at the III National Congress of Biological Psychiatry, 18–20 June 2000, Cappadocia, Turkey.


American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed.Washington (DC): APA; 1994.Google Scholar
Arkonaç, O.Turkish version of extrapyramidal symptoms rating scale (ESRS). In: Aydemir, O, Koroglu, E, editors. Psikiyatride kullanilan klinik olcekler (translation: clinical scales used in psychiatry). Ankara: Hekimler yayin birligi. 2000. p. 88–92.Google Scholar
Arranz, MJ, Munro, J, Owen, MJ, Spurlock, G, Sham, PC, Zhao, J, et al. Evidence for association between polymorphism in the promoter and coding regions of the 5-HT2A receptor gene and response to clozapine. Mol Psychiatry 1998;3:61–6.10.1038/ ScholarPubMed
Basile, VS, Masellis, M, Badri, F, Paterson, AD, Meltzer, HY, Lieberman, JA, et al. Association of the MscI polymorphism of the dopamine D3 receptor gene with tardive dyskinesia in schizophrenia. Neuropsychopharmacology 1999;21:17–27.10.1016/S0893-133X(98)00114-6CrossRefGoogle Scholar
Basile, VS, Ozdemir, V, Masellis, M,Walker, ML, Meltzer, HY, et al. A functional polymorphism of the cytochrome P450. A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia. Mol Psychiatry 2000;1(;5):410–7.10.1038/ Scholar
Basile, VS, Ozdemir, V, Masellis, M, Meltzer, HY, Lieberman, JA, Potkin, SG, et al. Lack of association between serotonin-2A receptor gene (HTR2A) polymorphisms and tardive dyskinesia in schizophrenia. Mol Psychiatry 2001;6:230–4.10.1038/ Scholar
Casey, DE.Neuroleptic-induced extrapyramidal syndromes and tardive dyskinesia. In: Hirsch, S,Weinberger, DR, editors. Schizophrenia. Oxford (UK): Blackwell; 1995. p. 546–65.Google Scholar
Chen, CH, Wei, FC, Koong, FJ, Hsiao, KJ.Association of Taq I polymorphism of dopamine D2 receptor gene and tardive dyskinesia in shizophrenia. Biol Psychiatry 1997;41:827–9.CrossRefGoogle Scholar
Chouinard, G, Ross-Chouinard, A.Extrapyramidal Rating Scale (ESRS). Montreal: The Autors; 1984.Google Scholar
Ellingrod, VL, Schultz, SK, Arndt, S.Association between cytochrome P450. D6 (CYP2D6) genotype antipsychotic exposure, and abnormal involuntary movement scale (AIMS) score. Psychiatry Genet 2000; 2(10):9–11.CrossRefGoogle Scholar
Guala, A, Mittino, D, Ghini, T, Quazza, G.Are metoclopramide dystonias familial?. Pediatr Med Chir 1992;14:617–8.Google ScholarPubMed
Herken, H, Uz, E, Özyurt, H, Sög¢üt, S, Virit, O, Akyol, Ö.Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia. Mol Psychiatry 2001;6:66–73.CrossRefGoogle ScholarPubMed
Hori, H, Ohmori, O, Shinkai, T, Kojima, H, Okano, C, Suzuki, T, et al. Manganese superoxide dismutase gene polymorphism and schizophrenia: relation to tardive dyskinesia. Neuropsychopharmacology 2000;23:170–7.CrossRefGoogle ScholarPubMed
Hu, S, Brody, CL, Fisher, C, Gunzerath, L, Nelson, ML, Sabol, SZ, et al. Interaction between the serotonin transporter gene and neuroticism in cigarette smoking behavior. Mol Psychiatry 2000;5:181–8.CrossRefGoogle ScholarPubMed
Jeste, DV, Caligiuri, MP.Tardive dyskinesia. Schizophr Bull 1993;19: 303–15.CrossRefGoogle ScholarPubMed
Karayiorgou, M, Altemus, M, Galke, BL, Goldman, D, Murphy, DL, Ott, J, et al. Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder. Proc Natl Acad Sci USA 1997;94:4572–5.10.1073/pnas.94.9.4572CrossRefGoogle ScholarPubMed
Kalow, W, Tang, BK.Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities. Clin Pharmacol Ther 1991; 50:508–19.CrossRefGoogle ScholarPubMed
Kalow, W, Tang, BK, Endrenyi, L.Hypothesis: comparison of inter and intra-individual variations can substitute for twin studies in drug research. Pharmacogenetics 1998;8:283–9.Google Scholar
Kalow, W, Tang, BK.Caffeine as a metabolic probe: exploration of enzyme-inducing effect of cigarette smoking. Clin Pharmacol Ther 1991;49:44–8.CrossRefGoogle ScholarPubMed
Kirch, DG, Alho, AM, Wyatt, RJ.Hypothesis: a nicotine-dopamine interaction linking smoking with Parkinson’s disease and tardive dyskinesia. Cell Mol Neurobiol 1988;8:285–91.CrossRefGoogle ScholarPubMed
Macciardi, F, Verga, M, Cavallaro, R, Pedrini, S, Cohen, S, Smeral, di E.A genetic study of tardive dyskinesia in an İtalian population of chronic schizophrenics.Proceeding of World Congress on Psychiatric Genetics, San Francisco, Psychiatric Genetics; 1996.CrossRefGoogle Scholar
Miller, M, Opheim, KE, Raisys, VA, Motulsky, AG.Teophylline metabolism: variation and genetics. Clin Pharmacol Ther 1984;35: 170–82.Google Scholar
Rosengarten, H, Schweitzer, JW, Friedhoff, AJ.Possible genetic factors underlying the pathophysiology of tardive dyskinesia. Pharmacol Biochem Behav 1994;49:663–7.CrossRefGoogle ScholarPubMed
Rosengarten, H, Schweitzer, JW, Friedhoff, AJ.A mechanism underlying neuroleptic-induced oral dyskinesias in rats. Pol J Pharmacol 1993;45:391–8.Google ScholarPubMed
Rosengarten, H, Schweitzer, JW, Friedhoff, AJ.A sub population of the dopamine D1 receptors mediate repetetive jaw movements in rats. Pharmacol Biochem Behav 1993;45:921–4.Google Scholar
Sachdev, PS.The current status of the tardive dyskinesia. Aust New Zealand J Psychiatry 2000;34:355–69.CrossRefGoogle ScholarPubMed
Saltz, BL, Kane, JM,Woerner, MG, Lieherman, JA,Alvir, JJ.Aging and tardive dyskinesia. In: Yassa, R, Nair, NPV, Jeste, DV, editors. Neuroleptic-induced movement disorders. New York: Cambridge University Press; 1997. p. 13–25.Google Scholar
Schooler, NR, Kane, JM.Research diagnoses for tardive dyskinesia. Arch Gen Psychiat 1982;39:486–7.Google ScholarPubMed
Segman, RH, Heresco-Levy, U, Finkel, B, Goltser, T, Shalem, R, Schlafman, M, et al. Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia. Mol Psychiatry 2001;6: 225–9.10.1038/ ScholarPubMed
Strous, RD, Bark, N,Woerner, M, Lachman, HM.Lack of association of a functional catechol-O-methyltransferase gene polymorphism in schizophrenia. Biol Psychiatry 1997;41:493–5.10.1016/S0006-3223(96)00474-XCrossRefGoogle Scholar
Swartz, JR, Burgoyne, K, Smith, M, Gadasaly, R, Ananth, J, Anantk, K.Tardive dyskinesia and ethnicity: review of the literature. Ann Clin Psychiatry 1997;9:53–9.CrossRefGoogle ScholarPubMed
Tsai, G, Goff, DC, Chang, RW, Flood, J, Baer, L, Coyle, JT.Markers of glutamaterjic neurotransmission and oxidative stress associated with tardive dyskinesia. Am J Psychiatry 1998;155:1207–13.10.1176/ajp.155.9.1207CrossRefGoogle ScholarPubMed
Tut, GT, Wang, JL, Lim, CCL.Negative association between T102C polymorphism at the 5-HT2A receptor gene and bipolar affective disorders in Singaporen Chinese. J Affect Dis 2000;58:211–4.10.1016/S0165-0327(99)00104-4CrossRefGoogle ScholarPubMed
O’Callaghan, E, Larkin, C, Kinsella, A, Waddington, JL.Obstetric complications, the putative familial-sporadic distinction, and tardiv dyskinesia in schizophrenia. Br J Psychiatry 1990;157:578–84.10.1192/bjp.157.4.578CrossRefGoogle Scholar
Ohmori, O, Suzuki, T, Kojima, H, Shinkai, T, Terao, T, Mita, T, et al. Tardive dyskinesia and debrisoquine 4-hydroxylase (CYP2D6) genotype in Japanese schizophrenics. Schizophrenia Research 1998;32: 107–13.10.1016/S0920-9964(98)00018-8CrossRefGoogle ScholarPubMed
Waddington, JL,Youssef, HA.The expression of schizophrenia, affective disorder, and vulnerability to tardive dyskinesia in an extensive pedigree. Br J Psychiatry 1988;153:376–81.CrossRefGoogle Scholar
Yamada, K, Kanba, S, Anamizu, S, Ohnichi, K, Ashikari, J,Yagi, G, et al. Low superoxide dismutase in schizophrenic patients with tardive dyskinesia. Psychol Med 1997;27:1223–5.CrossRefGoogle ScholarPubMed
Yassa, R, Lal, S, Korpassy, A, Ally, J.Nicotine exposure and tardive dyskinesia. Biol Psychiatry 1987;22:67–72.Google ScholarPubMed
Yilmaz, M, Erdal, ME, Herken, H, Çataloluk, O, Barlas, Ö, Bayazit, Y.Significance of the serotonin transporter gene polymorphism in migraine. J Neurological Sci 2001;186:27–30.10.1016/S0022-510X(01)00491-9CrossRefGoogle ScholarPubMed
Submit a response


No Comments have been published for this article.