Schizophrenia Research
Volume 47, Issue 1 , Pages 49-58 , 15 January 2001

Lack of association between the T→C 267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia

  • Mario Masellis

      Affiliations

    • Neurogenetics Section, Clarke Division, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ont. M5T 1R8, Canada
  • ,
  • Vincenzo S Basile

      Affiliations

    • Neurogenetics Section, Clarke Division, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ont. M5T 1R8, Canada
  • ,
  • Herbert Y Meltzer

      Affiliations

    • Department of Psychiatry, Vanderbilt University, Nashville, TN, USA
  • ,
  • Jeffrey A Lieberman

      Affiliations

    • Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA
  • ,
  • Serge Sevy

      Affiliations

    • Department of Veteran Affairs, The Bronx Veteran's Administrative Medical Center, New York, NY, USA
  • ,
  • David A Goldman

      Affiliations

    • Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA
  • ,
  • Mark W Hamblin

      Affiliations

    • GRECC, VA Puget Sound Health Care System, and Department of Psychiatry and Behavioural Sciences, University of Washington, Seattle WA, USA
  • ,
  • Fabio M Macciardi

      Affiliations

    • Neurogenetics Section, Clarke Division, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ont. M5T 1R8, Canada
  • ,
  • James L Kennedy

      Affiliations

    • Neurogenetics Section, Clarke Division, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ont. M5T 1R8, Canada
    • Corresponding Author InformationCorresponding author. Tel.: +1-416-979-4987; fax: +1-416-979-4666

Received 13 July 1999 ,Accepted 7 January 2000.

References 

  1. Arranz M, Collier D, Sodhi M, Ball D, Roberts G, Price J, et al. Association between clozapine response and allelic variation in 5-HT2A receptor gene. Lancet. 1995;346:281–282
  2. Arranz MJ, Collier DA, Munro J, Sham P, Kirov G, Sodhi M, et al. Analysis of a structural polymorphism in the 5-HT2A receptor and clinical response to clozapine. Neuroscience Letters. 1996;217:177–178
  3. Arranz MJ, Munro J, Owen MJ, Spurlock G, Sham PC, Zhao J, et al. Evidence for association between polymorphisms in the promoter and coding regions of the 5-HT2A receptor gene and response to clozapine. Molecular Psychiatry. 1998;3(1):61–66
  4. Ashby CR, Wang RY. Pharmacological actions of the atypical antipsychotic drug clozapine: a review. Synapse. 1996;24(4):349–394
  5. 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(1):17–27
  6. Benca RM. Sleep in psychiatric disorders. Neurologic Clinics. 1996;14(4):739–764
  7. Bengtsson HJ, Kullberg A, Millan MJ, Hjorth S. The role of 5-HT1a autoreceptors and alpha 1-adrenoceptors in the modulation of 5-HT release — III. Clozapine and the novel putative antipsychotic S 16924. Neuropharmacology. 1998;37:349–356
  8. Bennett ST, Lucassen AM, Gough SC, Powell EE, Undlien DE, Pritchard LE, et al  Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus. Nature Genetics. 1995;9(3):284–292
  9. Bleehen T. Clozapine: Literature Review. Basle: Sandoz Pharma Ltd; 1993;
  10. Bolos AM, Goldman D, Dean M. Dinucleotide repeat and alu repeat polymorphisms at the 5-HT1A (HTR1A) receptor gene. Psychiatric Genetics. 1993;3:235–240
  11. Brett PM, Curtis D, Robertson MM, Gurling HM. Exclusion of the 5-HT1A serotonin neuroreceptor and tryptophan oxygenase genes in a large British kindred multiply affected with Tourette's syndrome, chronic motor tics and obsessive–compulsive behavior. American Journal of Psychiatry. 1995;152(3):437–440
  12. Broekkamp CL, Oosterloo SK, Berendsen HH, van Delft AM. Effect of metergoline, fenfluramine, and 8-OHDPAT on catalepsy induced by haloperidol or morphine. Naunyn–Schmiedebergs Archives of Pharmacology. 1988;338(2):191–195
  13. Casey DE. The effect of 8-OH DPAT on haloperidol-induced dystonia in non-human primates. Paper presented at 31st Annual Meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico. 1992;
  14. Casey DE. Extrapyramidal syndromes: primate models as predictors of clinical response. Paper presented at 33rd Annual Meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico. 1994;
  15. Eglen RM, Jasper JR, Chang DJ, Martin GR. The 5-HT7 receptor: orphan found. Trends in Pharmacological Sciences. 1997;18(4):104–107
  16. Erdmann J, Shimron-Abarbanell D, Cichon S, Albus M, Maier W, Lichtermann D, et al  Systematic screening for mutations in the promoter and the coding region of the 5-HT1A gene. American Journal of Medical Genetics. 1995;60(5):393–399
  17. 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. Molecular Psychiatry. 1996;1:392–397
  18. Gelernter J, Rao PA, Pauls DL, Hamblin MW, Sibley DR, Kidd KK. Assignment of the 5HT7 receptor gene (HTR7) to chromosome 10q and exclusion of genetic linkage with Tourette syndrome. Genomics. 1995;26(2):207–209
  19. Glatt CE, Snowman AM, Sibley DR, Snyder SH. Clozapine: selective labeling of sites resembling 5HT6 serotonin receptors may reflect psychoactive profile. Molecular Medicine. 1995;1(4):398–406
  20. Hicks PB. The effect of serotonergic agents on haloperidol-induced catalepsy. Life Sciences. 1990;47(18):1609–1615
  21. Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, et al. International union of pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacological Reviews. 1994;46(2):157–203
  22. Inayama Y, Yoneda H, Inada Y, Sakai J, Koh J, Hayashi K, et al. HTR1A pro16/leu16 polymorphism in bipolar affective disorder. Paper presented at World Congress on Psychiatric Genetics, Cardiff, UK. 1995;
  23. Invernizzi RW, Cervo L, Samanin R. 8-Hydroxy-2-(di-n-propylamino) tetralin, a selective serotonin1A receptor agonist, blocks haloperidol-induced catalepsy by an action on raphe nuclei medianus and dorsalis. Neuropharmacology. 1988;27(5):515–518
  24. Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Archives of General Psychiatry. 1988;45:789–796
  25. Kapur S, Remington G. Serotonin–dopamine interaction and its relevance to schizophrenia. American Journal of Psychiatry. 1996;153:466–476
  26. Khan MA, Isenberg KE, Aschauer H, Devor EJ. A Sac I RFLP is detected with the 5-HT1a serotonin receptor probe G21. Nucleic Acids Research. 1990;18(3):691
  27. Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, et al. Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor. Journal of Neurochemistry. 1996;66(1):47–56
  28. Kuroki T, Meltzer HY, Ichikawa J. Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucelus accumbens. Journal of Pharmacology and Experimental Therapeutics. 1998;288:774–781
  29. Lahiri DK, Nurnberger JI. A rapid non-enzymatic method for the preparation of HMV DNA from blood for RFLP studies. Nucleic Acids Research. 1991;19(19):5444
  30. Lam S, Shen Y, Nguyen T, Messier TL, Brann M, Comings D, et al. A serotonin receptor gene (5HT1A) variant found in a Tourette's syndrome patient. Biochemical and Biophysical Research Communications. 1996;219(3):853–858
  31. Liebman JM, Gerhardt SC, Gerber R. Effects of 5-HT1A agonists and 5-HT2 antagonists on haloperidol-induced dyskinesias in squirrel monkeys: no evidence for reciprocal 5-HT–dopamine interaction. Psychopharmacology. 1989;97(4):456–461
  32. Lin CH, Tsai SJ, Yu YW, Song HL, Tu PC, Sim CB, et al. No evidence for association of serotonin-2A receptor variant (102 T/C) with schizophrenia or clozapine response in a Chinese population. Neuro. Report. 1999;10:57–60
  33. Lovenberg TW, Baron BM, de Lecea L, Miller JD, Prosser RA, Rea MA, et al. A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythyms. Neuron. 1993;11:449–458
  34. Malhotra AK, Goldman D, Ozaki N, Breier A, Buchanan R, Pickar D. Lack of associaton between polymorphisms in the 5-HT2A receptor gene and the antipsychotic response to clozapine. American Journal of Psychiatry. 1996;153(8):1092–1094
  35. Malhotra AK, Goldman D, Ozaki N, Rooney W, Clifton A, Buchanan RW, et al. Clozapine response and the 5HT(2C)Cys(23)Ser polymorphism. Neuroreport. 1996;7(13):2100–2102
  36. Masellis M, Paterson AD, Badri F, Lieberman JA, Meltzer HY, Cavazzoni P, et al. Genetic variation of 5-HT2A receptor and response to clozapine. Lancet. 1995;346:1108
  37. Masellis M, Basile V, Meltzer HY, Lieberman JA, Sevy S, Macciardi FM, et al. Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients. Neuropsychopharmacology. 1998;19(2):123–132
  38. Masellis M, Basile VS, Ozdemir V, Meltzer HY, Macciardi FM, Kennedy JL. Pharmacogenetics of antipsychotic treatment: lessons learned from clozapine. Biological Psychiatry. 1999;47:252–266
  39. McGuffin P, Owen MJ, Farmer AE. Genetic basis of schizophrenia. Lancet. 1995;346(8976):678–682
  40. Melmer G, Sherrington R, Mankoo B, Kalsi G, Curtis D, Gurling HM. A cosmid clone for the 5HT1A receptor (HTR1A) reveals a TaqI RFLP that shows tight linkage to dna loci D5S6, D5S39 and D5S76. Genomics. 1991;11(3):767–769
  41. Meltzer HY. An overview of the mechanism of action of clozapine. Journal of Clinical Psychiatry. 1994;55(suppl. B):47–52
  42. Meltzer HY. Role of serotonin in the action of atypical antipsychotic drugs. Clinical Neuroscience. 1995;3:64–75
  43. Meltzer HY. Predictors of response to clozapine. Psychiatric Annals. 1996;26(7):385–389
  44. Meltzer HY. The role of serotonin in antipsychotic drug action. Neuropsychopharmacology. 1999;21(2S):106–115
  45. Nakhai B, Nielsen DA, noila M, Goldman D. Two naturally occurring amino acid substitutions in the human 5-HT1A receptor: glycine 22 to serine 22 and isoleucine 28 to valine 28. Biochemical and Biophysical Research Communications. 1995;210(2):530–536
  46. Neal-Beliveau BS, Joyce JN, Lucki I. Serotonergic involvement in haloperidol-induced catalepsy. Journal of Pharmacology and Experimental Therapeutics. 1993;265(1):207–217
  47. Newman-Tancredi A, Chaput C, Verriele L, Millan MJ. Clozapine is a partial agonist at cloned, human serotonin 5-HT1A receptors. Neuropharmacology. 1996;35(1):119–121
  48. Nothen MM, Rietschel M, Erdmann J, Oberlander H, Moller HJ, Naber D, et al. Genetic variation of the 5-HT2A receptor and response to clozapine. Lancet. 1995;346:908–909
  49. Ozdemir V, Masellis M, Basile VS, Kalow W, Meltzer HY, Lieberman JA, et al. Variability in response to clozapine: potential role of cytochrome P450 1A2 and the dopamine D4 receptor gene. CNS Spectrums. 1999;4(6):30–56
  50. Pesonen U, Koulu M, Eggert M, Virkunnen M, Linnoila M, Goldman D. Rare non-conservative amino acid substitution in the 5-HT7 receptor gene found in alcoholics with antisocial personality disorder. Paper presented at 25th Annual Meeting of the Society for Neuroscience, San Diego. 1995;
  51. Pesonen U, Koulu M, Bergen A, Eggert M, Naukkarinen H, Virkkunen M, et al. Mutation screening of the 5-hydroxytryptamine7 receptor gene among Finnish alcoholics and controls. Psychiatry Research. 1998;77(3):139–145
  52. Rietschel M, Naber D, Fimmers R, Moeller HJ, Propping P, Noethen MM. Efficacy and side-effects of clozapine not associated with variation in the 5-HT2C receptor. Neuroreport. 1997;8:1999–2003
  53. Rietschel M, Kennedy JL, Macciardi F, Meltzer HY  The Consensus Group for Outcome Measures in Psychoses for Pharmacological Studies . Application of Pharmacogenetics to Psychotic Disorders: the First Consensus Conference, 12 July 1998, Glasgow. Schizophrenia Research. 1999;37(2):191–196
  54. Rollema H, Lu Y, Schmidt AW, Zorn SH. Clozapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation. European Journal of Pharmacology. 1997;338:R3–R5
  55. 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. Journal of Pharmacology and Experimental Therapeutics. 1994;268(3):1403–1410
  56. Sodhi MS, Arranz MJ, Curtis D, Ball DM, Sham P, Roberts GW, et al. Association between clozapine response and allelic variation in the 5-HT2C receptor gene. Neuroreport. 1995;7(1):169–172
  57. Tremblay PO, Gervai SJ, Rouillard C. Modification of haloperidol-induced pattern of c-fos expression by serotonin. European Journal of Neuroscience. 1998;1:3546–3555
  58. Wadenberg ML. Antagonism by 8-OH-DPAT, but not ritanserin, of catalepsy induced by SCH 23390 in the rat. Journal of Neural Transmission General Section. 1992;89:49–59
  59. Wadenberg ML, Ahlenius S. Antipsychotic-like profile of combined treatment with raclopride and 8-OH-DPAT in the rat: enhancement of antipsychotic-like effects without catalepsy. Journal of Neural Transmission General Section. 1991;83(12):43–53
  60. Warren JT, Peacock ML, Fink JK. An RsaI polymorphism in the human serotonin receptor gene (HTR1A): detection by DGGE and RFLP analysis. Human Molecular Genetics. 1992;1(9):778
  61. Xie DW, Deng ZL, Ishigaki T, Nakamura Y, Suzuki Y, Miyasato K, et al. The gene encoding the 5-HT1A receptor is intact in mood disorders. Neuropsychopharmacology. 1995;12(3):263–268
  62. Ying SW, Rusak B. 5-HT7 receptors mediate serotonergic effects on light-sensitive suprachiasmatic nucleus neurons. Brain Research. 1997;755(2):246–254
  63. 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(6):1231–1233

PII: S0920-9964(00)00016-5

Schizophrenia Research
Volume 47, Issue 1 , Pages 49-58 , 15 January 2001