Schizophrenia Research
Volume 67, Issue 1 , Pages 63-70 , 1 March 2004

Risperidone response and 5-HT6 receptor gene variance: genetic association analysis with adjustment for nongenetic confounders

  • Hsien-Yuan Lane

      Affiliations

    • Corresponding Author Information Corresponding author. Department of Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan. Tel.: +886-4-22062121; fax: +886-4-22361042.
    • Department of Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan
    • Department of Medical Research, China Medical University Hospital, Institute of Medical Sciences, China Medical University, Taichung, Taiwan
    • ,
  • Cheng-Chieh Lin

      Affiliations

    • Department of Medical Research, China Medical University Hospital, Institute of Medical Sciences, China Medical University, Taichung, Taiwan
    • ,
  • Chiung-Hsien Huang

      Affiliations

    • Department of Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan
    • Department of Medical Research, China Medical University Hospital, Institute of Medical Sciences, China Medical University, Taichung, Taiwan
    • ,
  • Yue-Cune Chang

      Affiliations

    • Department of Mathematics, Tamkang University, Taipei, Taiwan
    • ,
  • Shih-Kuan Hsu

      Affiliations

    • Department of Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan
    • ,
  • Wen-Ho Chang

      Affiliations

    • Department of Psychiatry, Tzu-Chi University, Hualien, Taiwan

Received 15 May 2003 ,Accepted 24 August 2003.

References 

  1. American Psychiatric Association. Structured Clinical Interview for DSM-IV. Washington, DC: American Psychiatric Press; 1994;
  2. Andreasen NC. Positive vs. negative schizophrenia: a critical evaluation. Schizophr. Bull. 1985;11:380–389
  3. Arranz MJ, Munro J, Osborne S, Collier D, Kerwin RW. Difficulties in replication of results. Lancet. 2000;356:1359–1360
  4. Basile VS, Masellis M, Potkin SG, Kennedy JL. Pharmacogenomics in schizophrenia: the quest for individualized therapy. Hum. Mol. Genet. 2002;11:2517–2530
  5. Branchek TA, Blackburn TP. 5-HT6 receptors as emerging targets for drug discovery. Annu. Rev. Pharmacol. Toxicol. 2000;40:319–334
  6. Chang WH, Chen TY, Lin SK, Lung FW, Lin WL, Hu WH, et al. Plasma catecholamine metabolites in schizophrenics: evidence for the two-subtype concept. Biol. Psychiatry. 1990;27:510–518
  7. Chouinard G, Ross-Chouinard A, Annable L, Jones BD. The extrapyramidal symptom rating scale. Can. J. Neurol. Sci. 1980;7:33
  8. East SZ, Burnet PW, Kerwin RW, Harrison PJ. An RT-PCR study of 5-HT6 and 5-HT7 receptor mRNAs in the hippocampal formation and prefrontal cortex in schizophrenia. Schizophr. Res. 2002;57:15–26
  9. Erdmann J, Nothen MM, Shimron-Abarbanell D, Rietschel M, Albus M, Borrmann M, et al. The human serotonin 7 (5-HT7) receptor gene: genomic organization and systematic mutation screening in schizophrenia and bipolar affective disorder. Mol. Psychiatry. 1996;1:392–397
  10. Holden C. Deconstructing schizophrenia. Science. 2003;299:333–335
  11. Jann MW, Grimsley SR, Gray EC, Chang WH. Pharmacokinetics and pharmacodynamics of clozapine. Clin. Pharmacokinet. 1993;24:161–176
  12. Kapur S, Seeman P. Does fast dissociation from the dopamine D2 receptor explain the action of atypical antipsychotics?: a new hypothesis. Am. J. Psychiatry. 2001;158:360–369
  13. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull. 1987;13:261–276
  14. Kiberstis P, Roberts L. It's not just the genes. Science. 2002;296:685
  15. Lane HY, Deng HC, Huang SM, Hu WH, Chang WH, Hu OYP. Low frequency of dextromethorphan O-demethylation deficiency in a Chinese population. Clin. Pharmacol. Ther. 1996;60:696–698
  16. Lane HY, Chiu WC, Chang WH. Risperidone monotherapy for mania and depression. Am. J. Psychiatry. 1999;156:1115
  17. Lane HY, Chiu WC, Chou JCY, Wu ST, Su MH, Chang WH. Risperidone in acutely exacerbated schizophrenia: dosing strategies and plasma levels. J. Clin. Psychiatry. 2000;61:209–214
  18. Lane HY, Chang YC, Chiu CC, Chen TT, Lee SH, Chang WH. Influences of patient-related variables on risperidone efficacy for acutely exacerbated schizophrenia: analyses with rigorous statistics. J. Clin. Psychopharmacol. 2002;22:353–358
  19. Lane HY, Guo SC, Hwang TJ, Chen YS, Cheng JJ, Lee YC, et al. Olanzapine plasma levels and antidepressant effects in schizophrenic patients. J. Clin. Psychopharmacol. 2002;22:530–532
  20. Lane HY, Chang YC, Chiu CC, Chen ML, Hsieh MH, Chang WH. Association of risperidone treatment response with a polymorphism in the 5-HT2A receptor gene. Am. J. Psychiatry. 2002;159:1593–1595
  21. Lane HY, Chang YC, Cheng YC, Liu GC, Lin XR, Chang WH. Effects of patient demographics, risperidone dosage, and clinical outcome on body weight in acutely exacerbated schizophrenia patients. J. Clin. Psychiatry. 2003;64:316–320
  22. Leucht S, Pitschel-Walz G, Abraham D, Kissling W. Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. Schizophr. Res. 1999;35:51–68
  23. Lieberman JA, Safferman AZ, Pollack S, Szymanski S, Johns C, Howard A, et al. Clinical effects of clozapine in chronic schizophrenia: response to treatment and predictors of outcome. Am. J. Psychiatry. 1994;151:1744–1752
  24. Lieberman JA, Koreen AR, Chakos M, Sheitman B, Woerner M, Alvir JM, et al. Factors influencing treatment response and outcome of first-episode schizophrenia: implications for understanding the pathophysiology of schizophrenia. J. Clin. Psychiatry Suppl. 1996;9:5–9
  25. Lingjaerde O, Ahlfors UG, Bech P, Dencker SJ, Elgen K. The UKU side effect rating scale. A new comprehensive ration scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr. Scand., Suppl. 1987;334:1–100
  26. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat. Genet. 2003;33:177–182
  27. Lung FW, Tzeng DS, Shu BC. Ethnic heterogeneity in allele variation in the DRD4 gene in schizophrenia. Schizophr. Res. 2002;57:239–245
  28. Malhotra AK, Goldman D. Benefits and pitfalls encountered in psychiatric genetic association studies. Biol. Psychiatry. 1999;45:544–550
  29. Masellis M, Basile VS, Meltzer HY, Lieberman JA, Sevy S, Goldman DA, et al. Lack of association between the T→C 267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia. Schizophr. Res. 2001;47:49–58
  30. Matsumoto M, Togashi H, Mori K, Ueno K, Miyamoto A, Yoshioka M. Characterization of endogenous serotonin-mediated regulation of dopamine release in the rat prefrontal cortex. Eur. J. Pharmacol. 1999;383:39–48
  31. Meltzer HY. The role of serotonin in antipsychotic drug action. Neuropsychopharmacology. 1999;Suppl. 2:S106–S115
  32. Meltzer HY, Park S, Kessler R. Cognition, schizophrenia, and the atypical antipsychotic drugs. Proc. Natl. Acad. Sci. U. S. A. 1999;96:13591–135933
  33. Meneses A. Effects of the 5-HT6 receptor antagonist Ro 04-6790 on learning consolidation. Behav. Brain Res. 2001;18:107–110
  34. Messina D, Annesi G, Serra P, Nicoletti G, Pasqua A, Annesi F, et al. Association of the 5-HT6 receptor gene polymorphism C267T with Parkinson's disease. Neurology. 2002;58:828–829
  35. Otano A, Frechilla D, Cobreros A, Cruz-Orive LM, Insausti A, Insausti R, et al. Anxiogenic-like effects and reduced stereological counting of immunolabelled 5-hydroxytryptamine6 receptors in rat nucleus accumbens by antisense oligonucleotides. Neuroscience. 1999;92:1001–1009
  36. Polesskaya OO, Sokolov BP. Differential expression of the “C” and “T” alleles of the 5-HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics. J. Neurosci. Res. 2002;67:812–822
  37. Potkin SG, Fleming K, Jin Y, Gulasekaram B. Clozapine enhances neurocognition and clinical symptomatology more than standard neuroleptics. J. Clin. Psychopharmacol. 2001;21:479–483
  38. Pouzet B, Didriksen M, Arnt J. Effects of the 5-HT6 receptor antagonist, SB-271046, in animal models for schizophrenia. Pharmacol. Biochem. Behav. 2002;71:635–643
  39. Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ, Shen Y, et al. Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J. Pharmacol. Exp. Ther. 1994;268:1403–1410
  40. SAS Institute. SAS OnlineDoc(R), Version 8. Cary, NC: SAS Institute; 1999;
  41. Sawa A, Snyder SH. Schizophrenia: diverse approaches to a complex disease. Science. 2002;296:692–695
  42. Seeman MV, Lang M. The role of estrogens in schizophrenia gender differences. Schizophr. Bull. 1990;16:185–194
  43. Staddon S, Arranz MJ, Mancama D, Mata I, Kerwin RW. Clinical applications of pharmacogenetics in psychiatry. Psychopharmacology. 2002;162:18–23
  44. Strauss JS, Carpenter WT. The prediction of outcome in schizophrenia: I. Characteristics of outcome. Arch. Gen. Psychiatry. 1972;27:739–746
  45. Sullivan PF, Eaves LJ, Kendler KS, Neale MC. Genetic case-control association studies in neuropsychiatry. Arch. Gen. Psychiatry. 2001;58:1015–1024
  46. Szymanski S, Lieberman JA, Alvir JM, Mayerhoff D, Loebel A, Geisler S, et al. Gender differences in onset of illness, treatment response, course, and biologic indexes in first-episode schizophrenic patients. Am. J. Psychiatry. 1995;152:698–703
  47. Szymanski S, Lieberman J, Pollack S, Kane JM, Safferman A, Munne R, et al. Gender differences in neuroleptic nonresponsive clozapine-treated schizophrenics. Biol. Psychiatry. 1996;39:249–254
  48. Tollefson GD, Sanger TM, Lu Y, Thieme ME. Depressive signs and symptoms in schizophrenia: a prospective blinded trial of olanzapine and haloperidol. Arch. Gen. Psychiatry. 1998;55:250–258
  49. Tsai SJ, Liu HC, Liu TY, Wang YC, Hong CJ. Association analysis of the 5-HT6 receptor polymorphism C267T in Alzheimer's disease. Neurosci. Lett. 1999;276:138–139
  50. Vogt IR, Shimron-Abarbanell D, Neidt H, Erdmann J, Cichon S, Schulze TG, et al. Investigation of the human serotonin 6 (5-HT6) receptor gene in bipolar affective disorder and schizophrenia. Am. J. Med. Genet. 2000;96:217–221
  51. Yu YW, Tsai SJ, Lin CH, Hsu CP, Yang KH, Hong CJ. Serotonin-6 receptor variant (C267T) and clinical response to clozapine. NeuroReport. 1999;10:1231–1233
  52. Zeger SL, Liang KY, Albert PS. Models for longitudinal data: a generalized estimating equation approach. Biometrics. 1988;44:1049–1060

PII: S0920-9964(03)00265-2

doi: 10.1016/j.schres.2003.08.006

Schizophrenia Research
Volume 67, Issue 1 , Pages 63-70 , 1 March 2004

Article Tools