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A search for association between schizophrenia and dopamine-related alleles

  • E. Jönsson
  • S. Brené
  • Th. Geijer
  • L. Terenius
  • A. Tylec
  • M. -L. Persson
  • G. Sedvall
Original Paper

Abstract

Dopamine receptor dysfunction and altered tyrosine hydroxylase activity have both been implicated in the pathophysiology of schizophrenia. Schizophrenic pationts and control subjects were examined for allele frequencies in the tyrosine hydroxylase and dopamine D2 and D4 receptor genes. No significant differences of allele or genotype frequencies were found between the two groups after adjustment for multiple comparison. Neither were any significant relationships observed between allele frequencies and a number of clinical variables within the schizoprenic subsample. When no adjustment was made for multiple testing a few significant tendencies were obtained which warrant further research in extended patient and control materials. The results are compatible with the view that the tyrosine hydroxylase, dopamine receptor D2 and D4 gene polymorphisms examined are not of major importance in the aetiology or pathophysiology of schizophrenia.

Key words

Schizophrenia Association study Dopamine receptors (DRD2, DRD4) Tyrosine hydroxylase 

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References

  1. American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorder (DSM-III-R); 3rd edn, revised. American Psychiatric Press, Washington DCGoogle Scholar
  2. Antonarakis SE, Blouin J-L, Pulver AE, Wolyniec P, Lasseter VK, Nestadt G, Kasch L, Babb R, Kazazian HH, Dombroski B, Kimberland M, Ott J, Housman D, Karayiorgou M, MacLean CJ (1995) Schizophrenia susceptibility and chromosome 6p24-22. Nature Genet 11:235–236Google Scholar
  3. Arinami T, Itokawa M, Enguchi H, Tagaya H, Yano S, Shimizu H, Hamaguchi H, Toru M (1994) Association of dopamine D2 receptor molecular variant with schizophrenia. Lancet 343:703–704Google Scholar
  4. Asherson P, Williams N, Roberts E, McGuffin P, Owen M (1994) DRD2 Ser311/Cys311 polymorphism in schizophrenia. Lancet 343:1045Google Scholar
  5. Barr CL, Kennedy JL, Lichter JB, Van Tol HHM, Wetterberg L, Livak KJ, Kidd KK (1993) Alleles at the dopamine D4 receptor locus do not contribute to the genetic susceptibility to schizophrenia in a large Swedish pedigree. Am J Med Genet 48:218–222Google Scholar
  6. Campion D, d'Amato T, Bastard C, Laurent C, Guedj F, Jay M, Dollfus S, Thibaut F, Petit M, Gorwood P, Babron MC, Waksman G, Martinez M, Mallet J, (1994) Genetic study of dopamine D1, D2, and D4 receptors in schizophrenia. Psychiatry Res 51:215–230Google Scholar
  7. Castiglione CM, Deinard AS, Speed WC, Sirugo G, Rosenbaum HC, Zhang Y, Grandy DK, Grigorenko EL, Bonne-Tamir B, Pakstis AJ, Kidd JR, Kidd KK (1995) Evolution of haplotypes at the DRD2 locus. Am J Hum Genet 57:1445–1456Google Scholar
  8. Catalano M, Nobile M, Novelli E, Nöthen MM, Smeraldi E (1993) Distribution of a novel mutation in the first exon of the human dopamine D4 receptor gene in psychotic patients. Biol Psychiatry 34:459–464Google Scholar
  9. Cichon S, Nöthen MM, Rietschel M, Körner J, Propping P (1994) Single-strand conformation analysis (SSCA) of the dopamine D1 receptor gene (DRD1) reveals no significant mutation in patients with schizophrenia and manic depression. Biol Psychiatry 36:850–853Google Scholar
  10. Cichon S, Nöthen MM, Lanczik M, Rietschel M, Körner J, Erdmann J, Propping P (1993) Association study of the repeat polymorphism in exon 3 of the dopamine D4 receptor gene in schizophrenia. Psychiatr Genet 3 (Abstract): 162–163Google Scholar
  11. Comings DE, Comings BG, Muhleman D, Shahbahrami B, Tast D, Knell E, Kocsis P, Baumgarten R, Kovacs BW, Levy DL, Smith M, Borison RL, Evans DD, Klein DN, MacMurray J, Tosk JM, Sverd J, Gysin R, Flanagan SD (1991) The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. J. Am Med Assoc 266:1793–1900Google Scholar
  12. Coon H, Byerly W, Holik J, Hoff M, Mylesworsley M, Lannfelt L, Sokoloff P, Schwartz JC, Waldo M, Freedman R, Plaetke R (1993) Linkage analysis of schizophrenia with five dopamine receptor genes in nine pedigrees. Am J Hum Genet 52:327–334Google Scholar
  13. Crocq M-A, Mant R, Asherson P, Williams J, Hode Y, Mayerova A, Collier D, Lannfelt L, Sokoloff P, Schwartz J-C, Gill M, Macher J-P, McGuffin P, Owen MJ (1992) Association between schizophrenia and homozygosity at the dopamine D3 receptor gene. J Med Genet 29:858–860Google Scholar
  14. Daniels J, Williams J, Asherson P, McGuffin P, Owen M (1995) No association between schizophrenia and polymorphisms within the genes for debrisoquine 4-hydroxylase (CYP2D6) and the dopamine transporter (DAT). Am J Med Genet 60:85–87Google Scholar
  15. Daniels J, Williams J, Mant R, Asherson P, McGuffin P, Owen MJ (1994) Repeat length variation in the dopamine D4 receptor gene shows no evidence of association with schizophrenia. Am J Med Genet 54:256–258Google Scholar
  16. Daniels JK, Williams NM, Williams J, Jones LA, Cardno AG, Murphy KC, Spurlock G, Riley B, Scambler P, Asherson P, McGuffin P, Owen MJ (1996) No evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol-0-methyltransferase activity. Am J Psychiatry 153:268–270Google Scholar
  17. Davis KL, Kahn RS, Ko G, Davidson M (1991) Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 148:1474–1486Google Scholar
  18. Farde L, Wiesel F-A, Stone-Elander S, Halldin C, Nordström A-L, Hall H, Sedvall G (1990) D2 dopamine receptors in neuroleptic-naive schizophrenic patients. Arch Gen Psychiatry 47:213–219Google Scholar
  19. Geijer T, Neiman J, Rydberg U, Gyllander A, Jönsson E, Sedvall G, Valverius P, Terenius L (1994) Dopamine D2 receptor gene polymorphisms in Scandinavian chronic alcoholics. Eur Arch Psychiatry Clin Neurosci 244:26–32Google Scholar
  20. Gill M, McGuffin P, Parfitt E, Mant R, Asherson P, Collier D, Vallada H, Powell J, Shaikh S, Taylor C, Sargeant M, Clements A, Nanko S, Takazawa N, Llewellyn D, Williams J, Whatley S, Murray R, Owen M (1993) A linkage study of schizophrenia with DNA markers from the long arm of chromosome 11. Psychol Med 23:27–44Google Scholar
  21. Grandy DK, Litt M, Allen L, Bunzow JR, Marcionni M, Makam H, Reed L, Magenis RE, Civelli O (1989) The human dopamine D2 receptor gene is located on chromosome 11 at q22–q23 and identifies a TaqI RFLP. Am J Hum Genet 45:778–785Google Scholar
  22. Griffon N, Crocq MA, Pilon C, Martres MP, Mayerova A, Uyanik G, Burgert E, Duval F, Macher JP, Javoy-Agid F, Tamminga CA, Schwartz JC, Sokoloff P (1996) Dopamine D3 receptor gene: organization, transcript variants, and polymorphism associated with schizophrenia. Am J Med Genet 67:63–70Google Scholar
  23. Griffon N, Sokoloff P, Diaz J, Lévesque D, Sautel F, Schwartz J-C, Simon P, Costentin J, Garrido F, Mann A, Wermuth C (1995) The dopamine D3 receptor and schizophrenia: pharmacological, anatomical and genetic approaches. Eur Neuropsychopharmacol Suppl:3–9Google Scholar
  24. Hallmayer J, Maier W, Schwab S, Ertl MA, Minges J, Ackenheil M, Lichtermann D, Wildenauer DB (1994) No evidence of linkage between the dopamine D2 receptor gene and schizophrenia. Psychiatry Res 53:203–215Google Scholar
  25. Haracz JL (1982) The dopamine hypothesis: an overview of studies with schizophrenic patients. Schizophr Bull 8:438–459Google Scholar
  26. Hattori M, Kuwata S, Tokunaga K, Sasaki T, Kazamatsuri H, Juji T, Nanko S (1993) Association study of schizophrenia with D11S35 and dopamine D2 receptor gene loci using dinucleotide repeat polymorphisms. Psychiatr Genet 3:247–252Google Scholar
  27. Hauge XY, Grandy DK, Eubanks JH, Evans GA, Civelli O, Litt M (1991) Detection and characterization of additional DNA polymorphisms in the dopamine D2 receptor gene. Genomics 10: 527–530Google Scholar
  28. Hess EJ, Bracha HS, Kleinman JE, Creese I (1987) Dopamine receptor subtype imbalance in schizophrenia. Life Sci 40:1487–1497Google Scholar
  29. Jensen S, Plaetke R, Holik J, Hoff M, Myles-Worsley M, Leppert M, Coon H, Vest K, Freedman R, Waldo M, Zhou Q-Y, Litt M, Civelli O, Byerley W (1993) Linkage analysis of schizophrenia: The D1 dopamine receptor gene and several flanking DNA markers. Hum Hered 43:58–62Google Scholar
  30. Jönsson E, Lannfelt L, Sokoloff P, Schwartz J-C, Sedvall G (1993) Lack of association between schizophrenia and alleles in the dopamine D3 receptor gene. Acta Psychiatr Scand 87:343–359Google Scholar
  31. Jönsson E, Sedvall G, Brené S, Gustavsson JP, Geijer T, Terenius L, Crocq M-A, Lannfelt L, Tylec A, Sokoloff P, Schwartz JC, Wiesel F-A (1996) Genotypes for dopamine receptors and tyrosine hydroxylase and their relationships to monoamine metabolites in CSF from healthy volunteers. Biol Psychiatry (in press)Google Scholar
  32. Kalsi G, Sherrington R, Mankoo BS, Brynjolfsson J, Sigmundsson T, Curtis D, Read T, Murphy P, Butler R, Petursson H, Gurling HMD (1996) Linkage study of the D5 dopamine receptor gene (DRD5) in multiplex Icelandic and English schizophrenia pedigrees. Am J Psychiatry 153:107–109Google Scholar
  33. Kendler KS, Diehl SR (1993) The genetics of schizophrenia: a current, genetic-epidemiologic perspective. Schizophr Bull 19:261–285Google Scholar
  34. Kendler KS, McGuire M, Gruenberg AM, O'Hare A, Spellman M, Walsh D (1993a) The Roscommon Family Study I. Methods, diagnosis of probands, and risk of schizophrenia in relatives. Arch Gen Psychiatry 50:527–540Google Scholar
  35. Kendler KS, McGuire M, Gruenberg AM, O'Hare A, Spellman M, Walsh D (1993b) The Roscommon family study, III. Schizophrenia-related personality disorders in relatives. Arch Gen Psychiatry 50:781–788Google Scholar
  36. Kendler KS, McGuire M, Gruenberg AM, Spellman M, O'Hare A, Walsh D (1993c) The Roscommon family study II. The risk of nonschizophrenic nonaffective psychoses in relatives. Arch Gen Psychiatry 50:645–652Google Scholar
  37. Kendler KS, McGuire M, Gruenberg AM, Walsh D (1995a) Schizotypal symptoms and signs in the Roscommon family study. Their factor structure and familial relationship with psychotic and affective disorders. Arch Gen Psychiatry 52:296–303Google Scholar
  38. Kendler KS, Neale MC, Walsh D (1995b) Evaluating the spectrum concept of schizophrenia in the Roscommon family study. Am J Psychiatry 152:749–754Google Scholar
  39. Kennedy JL, Billet EA, Maceiardi FM, Verga M, Parsons TJ, Meltzer HY, Lieberman J, Buchanan JA (1995) Association study of dopamine D3 receptor gene and schizophrenia. Am J Med Genet 60:558–562Google Scholar
  40. Kety SS, Rosenthal D, Wender PH (1978) Genetic relationships within the schizophrenia spectrum: evidence from adoption studies. In: Spitzer RL, Klein DF (eds) Critical issues in psychiatric diagnosis. Raven Press, New York, pp 213–223Google Scholar
  41. Kety SS, Rosenthal D, Wender PH, Schlusinger F (1968) The types and prevalence of mental illness in biological and adoptive families of adopted schizophrenics. In: Rosenthal D, Kety SS (eds) The transmission of schizophrenia. Pergamon Press, Oxford, pp 345–362Google Scholar
  42. Lasseter VK, Pulver AE, Wolyniec PS, Nestadt G, Meyers D, Karayiorgou M, Housman D, Antonarakis S, Kazazian H, Kasch L, Babb R, Kimberland M, Childs B (1995) Follow-up report of potential linkage for schizophrenia on chromosome 22q: part 3. Am J Med Genet 60:172–173Google Scholar
  43. Laurent C, Bodeau-Péan S, Campion D, d'Amato T, Jay M, Dollfus S, Thibault F, Petit M, Samolyk D, Martinez M, Mallet J (1994a) No major role for the dopamine D2 receptor Ser»-Cys311 mutation in schizophrenia. Psychiatry Genet 4:229–230Google Scholar
  44. Laurent C, Savoye C, Samolyk D, Meloni R, Mallet J, Campion D, Martinez M, d'Amato T, Bastard C, Dollfus S (1994b) Homozygosity at the dopamine D3 receptor locus is not associated with schizophrenia. J Med Genet 31:260Google Scholar
  45. Lee M-S, Lee H, Kwang-Yoon S (1995) Distribution of the TaqI polymorphism of the dopamine D2 receptor in a Korean schizophrenic population. Psychiatr Genet 5:S59Google Scholar
  46. Lee T, Seeman P (1980) Elevation of brain neuroleptic/dopamine receptors in schizophrenia. Am J Psychiatry 137:191–197Google Scholar
  47. Li T, Yang L, Wiese C, Xu CT, Zeng Z, Giros B, Caron MG, Moises HW, Liu X (1994) No association between alleles or genotypes at the dopamine transporter gene and schizophrenia. Psychiatry Res 52:17–23Google Scholar
  48. Lichter JB, Barr CL, Kennedy JL, Van Tol HHM, Kidd KK, Livak KJ (1993) A hypervariable segment in the human dopamine receptor D4 (DRD4) gene. Hum Molec Genet 2:767–773Google Scholar
  49. Macciardi F, Petronis A, Van Tol HHM, Marino C, Cavallini C, Smeraldi E, Kennedy JL (1994a) Analysis of the D4 dopamine receptor gene variant in an Italian schizophrenia kindred. Arch Gen Psychiatry 51:288–293Google Scholar
  50. Macciardi F, Verga M, Kennedy JL, Petronis A, Bersani G, Pancheri P, Smeraldi E (1994b) An association study between schizophrenia and the dopamine receptor genes DRD3 and DRD4 using haplotype relative risk. Hum Hered 44:328–336Google Scholar
  51. Maier W, Schwab S, Hallmayer J, Ertl MA, Minges J, Ackenheil M, Lichtermann D, Wildenauer D (1994) Absence of linkage between schizophrenia and the dopamine D4 receptor gene. Psychiatry Res 53:77–86Google Scholar
  52. Mant R, Williams J, Asherson P, Parfitt E, McGuffin P, Owen MJ (1994) Relationship between homozygosity at the dopamine D3 receptor gene and schizophrenia. Am J Med Genet 54:21–26Google Scholar
  53. Maziade M, Raymond V, Cliche D, Fournier JP, Caron C, Garneau Y, Nicole L, Marcotte P, Couture C, Simard C, Boivin R, Rodrigue C, Boutin P, Braekeleer M de, Martinez M, Mérette C (1995) Linkage results on 11q21–22 in eastern Quebec pedigrees densely affected by schizophrenia. Am J Med Genet 60: 522–528Google Scholar
  54. McGue M, Gottesman II (1991) The genetic epidemiology of schizophrenia and the design of linkage studies. Eur Arch Psychiatry Clin Neurosci 240:174–181Google Scholar
  55. Meloni R, Laurent C, Campion D, Ben Hadjali B, Thibaut F, Dollfus S, Petit M, Samolyk D, Martinez M, Poirier M-F, Mallet J (1995) A rare allele of microsatellite located in the tyrosine hydroxylase gene found in schizophrenic patients. C R Acad Sci Paris 318:803–809Google Scholar
  56. Meszaros K, Lenzinger E, Füreder T, Hornik K, Willinger U, Stompe T, Heiden AM, Resinger E, Fathi N, Gerhard E, Fuchs K, Miller-Reiter E, Pfersmann V, Sieghart W, Aschaurer HN, Kasper S (1996) Schizophrenia and the dopamine-β-hydroxylase gene: results of a linkage and association study. Psychiatr Genet 6:17–22Google Scholar
  57. Moises HW, Gelernter J, Giuffra LA, Zarcone V, Wetterberg L, Civelli O, Kidd KK, Cavalli-Sforza LL (1991) No linkage between D2 dopamine receptor gene region and schizophrenia. Arch Gen Psychiatry 48:643–647Google Scholar
  58. Moises HW, Yang L, Kristbjarnarson H, Wiese C, Byerly W, Maciardi F, Arolt V, Blackwood D, Liu X, Sjögren B, Aschauer HN, Hwu H-G, Jang K, Livesley WJ, Kennedy JL, Zoega T, Ivarsson O, Bui M-T, Yu M-H, Havsteen B, Commenges D, Weissenbach J, Schwinger E, Gottesman II, Pakstis AJ, Wetterberg L, Kidd KK, Helgason T (1995a) An international two-stage genome-wide search for schizophrenia susceptiblity genes. Nature Genet 11:321–324Google Scholar
  59. Moises HW, Yang L, Li T, Havsteen B, Fimmers R, Baur MP, Liu X, Gottesman II (1995b) Potential linkage disequilibrium between schizophrenia and locus D22S278 on the long arm of chromosome 22. Am J Med Genet 60:465–467Google Scholar
  60. Mulcrone J, Whatley SA, Marchbanks R, Wildenauer D, Altmark D, Daoud H, Gur E, Ebstein RP, Lerer B (1995) Genetic linkage analysis of schizophrenia using chromosome 11q13–24 markers in Israeli pedigrees. Am J Med Genet 60:103–108Google Scholar
  61. Nagatsu T, Levitt M, Udenfriend S (1964) Tyrosine hydroxylase: the initial step in norepinephrine biosynthesis. J Biol Chem 239:2910–2917Google Scholar
  62. Nakamura M, Inoue A, Hemmi H, Suzuki J (1995) Positive associations between dopamine D4 receptor polymorphism and schizophrenia — a study on two schizophrenic groups with genetic loading and unloading. Proc Jpn Acad Ser B Phys Biol Sci 71:241–243Google Scholar
  63. Nanko S, Fukuda R, Hattori M, Sasaki T, Dai XY, Yanaguchi K, Kazamatsuri H (1994a) Further evidence of no linkage between schizophrenia and the dopamine D3 receptor gene locus. Am J Med Genet 54:264–267Google Scholar
  64. Nanko S, Hattori M, Dai XY, Fukuda R, Kazamatsuri H (1994b) DRD2 Ser 311/Cys311 polymorphism in schizophrenia. Lancet 343:1044Google Scholar
  65. Nanko S, Hattori M, Ikeda K, Sasaki T, Kazamatsuri H, Kuwata S (1993a) Dopamine D4 receptor polymorphism and schizophrenia. Lancet 341:689–690Google Scholar
  66. Nanko S, Sasaki T, Fukuda R, Hattori M, Dai XY, Kazamatsuri H, Kuwata S, Juji T, Gill M (1993b) A study of association between schizophrenia and dopamine D3 receptor gene. Hum Genet 92:336–338Google Scholar
  67. Nicolini H, Sidenberg D, Camarena B, Guerra C, Monteiro Grazina M, Petronis A, Kennedy J (1993) Evaluation of dopaminergic system genes in Mexican schizophrenics. Rev Invest Clin 45:345–352Google Scholar
  68. Nimganokar VL, Sanders AR, Ganguli R, Zhang XR, Brar J, Hogge W, Fann WE, Patel PI, Chakravarti A (1996) Association study of schizophrenia and the dopamine D3 receptor gene locus in two independent samples. Am J Med Genet (in press)Google Scholar
  69. Nimgaonkar VL, Zhang XR, Caldwell JG, Ganguli R, Chakravarti A (1993) Association study of schizophrenia with dopamine D3 receptor gene polymorphisms: probable effects of family history? Am J Med Genet 48:214–217Google Scholar
  70. Nordström A-L, Farde L, Eriksson L, Halldin C (1995) No elevated D2 dopamine receptors in neuroleptic naive schizophrenic patients revealed by PET and [11C]NMSP. Psychiatr Res (Neuroimaging) 61:67–83Google Scholar
  71. Nöthen MM, Cichon S, Hemmer S, Hebebrand J, Remschmidt H, Lehmkuhl G, Poustka F, Schmidt M, Catalano M, Fimmers R, Körner J, Rietschel M, Propping P (1994a) Human dopamine D4 receptor gene: frequent occurrence of a null allele and observation of homozygosity. Hum Mol Genet 3:2207–2212Google Scholar
  72. Nöthen MM, Cichon S, Propping P, Fimmers R, Schwab SG, Wildenauer DB (1993a) Excess of homozygosity at the dopamine D3 receptor gene in schizophrenia not confirmed. J Med Genet 30:708Google Scholar
  73. Nöthen MM, Körner J, Lannfelt L, Sokoloff P, Schwartz J-C, Lanczik M, Rietschel M, Cichon S, Kramer R, Fimmers R, Möller H-J, Beckman H, Propping P, Grandy DK, Civelli O, O'Dowd BF (1993b) Lack of association between schizophenia and alleles of the dopamine D1, D2, D3 and D4 receptor loci. Psychiatry Genet 3:89–94Google Scholar
  74. Nöthen MM, Wildenauer D, Cichon S, Albus M, Maier W, Minger J, Lichtermann D, Bondy B, Rietschel M, Körner J, Fimmers R, Propping P (1994b) Dopamine D2 receptor molecular variant and schizophrenia. Lancet 343:1301–1302Google Scholar
  75. O'Hara BF, Smith SS, Bird G, Persico AM, Suarez BK, Cutting GR, Uhl GR (1993) Dopamine D2 receptor RFLPs, haplotypes and their association with substance use in black and caucasian research volunteers. Hum Hered 43:209–218Google Scholar
  76. Onstad S, Skre I, Torgersen S, Kringlen E (1991) Twin concordance for DSM-III-R schizophrenia. Acta Psychiatr Scand 83:395–401Google Scholar
  77. Persico AM, Wang ZW, Black DW, Andreasen NC, Uhl GR, Crowe RR (1995) Exclusion of close linkage between the synaptic vesicular monoamine transporter locus and schizophrenia spectrum disorders. Am J Med Genet 60:563–565Google Scholar
  78. Petronis A, Macciardi F, Athanassiades A, Paterson AD, Verga M, Meltzer HY, Cola P, Buchanan JA, Tol HHMV, Kennedy JL (1995) Association study between the dopamine D4 receptor gene and schizophrenia. Am J Med Genet 60:452–455Google Scholar
  79. Polymeropoulos MH, Coon H, Byerly W, Gershon ES, Goldin L, Crow TJ, Rubenstein J, Hoff M, Holik J, Smith AM, Shields G, Bass NJ, Poulter M, Lofthouse R, Vita A, Morganti C, Merril CR, DeLisi LE (1994) Search for schizophrenia susceptibility locus on human chromosome 22. Am J Med Genet 54:93–99Google Scholar
  80. Polymeropoulos MH, Xiao H, Rath DS, Merril CR (1991) Tetranucleotide repeat polymorphism at the human tyrosine hydroxylase gene (TH). Nucl Acids Res 19:3753Google Scholar
  81. Puers C, Hammond HA, Jin L, Caskey CT, Schumm JW (1993) Identification of repeat sequence heterogeneity at the polymorphic short tandem repeat locus HUMTH01[AATG]n and reassignment of alleles in population analysis by using a locus specific allelic ladder. Am J Hum Genet 53:953–958Google Scholar
  82. Rietschel M, Nöthen MM, Albus M, Maier W, Minges J, Bondy B, Körner J, Hemmer S, Fimmers R, Möller H-J, Wildenauer D, Propping P (1996) Dopamine D3 receptor Gly9/Ser9 polymorphism and schizophrenia: no increased frequency of homozygosity in German familial cases. Schizophr Res 20:181–186Google Scholar
  83. Rossum JM van (1967) The significance of dopamine-receptor blockade for the action of neuroleptic drugs. In: Brill H, Cole JO, Deniker P, Hippius H, Bradley PB (eds) Proc 5th Collegium Int Neuropsychopharmacologicum. Amsterdam. Excerpta Medica, Amsterdam pp 321–329Google Scholar
  84. Sabaté O, Campion D, d'Amato T, Martres MP, Sokoloff P, Giros B, Leboyer M, Jay M, Guedj F, Thibaut F, Dollfus S, Preterre P, Petit M, Babron M-C, Waksman G, Mallet J, Schwartz JC (1994) Failure to find evidence for linkage or association between the dopamine D3 receptor gene and schizophrenia. Am J Psychiatry 151:107–111Google Scholar
  85. Sanders AR, Rincon-Limas DE, Chakraborty R, Grandchamp B, Hamilton JD, Fann WE, Patel PI (1992) Association between genetic variation at the porphobilinogen deaminase gene and schizophrenia. Schizophr Res 8:211–221Google Scholar
  86. Schizophrenia Collaborative Linkage Group (chromosome 22), Coordinators: Gill M, Vallada H, Collier D (1996) A combined analysis of D22S278 marker alleles in affected sib-pairs: support for a susceptibility locus for schizophrenia at chromosome 22q12. Am J Med Genet 67:40–45Google Scholar
  87. Schwab SG, Albus M Hallmayer J, Hönig S, Borrmann M, Lichtermann D, Ebstein RP, Ackenheil M, Lerer B, Risch N, Maier W, Wildenauer DB (1995) Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib-pair linkage analysis. Nature Genet 11:325–327Google Scholar
  88. Seeman P, Guan H-C, Van Tol HHM (1993) Dopamine D4 receptors elevated in schizophrenia. Nature 365:441–445Google Scholar
  89. Shaikh S, Collier D, Arranz M, Ball D, Gill M, Kerwin R (1994a) DRD2 Ser311/Cys311 polymorphism in schizophrenia. Lancet 343:1045–1046Google Scholar
  90. Shaikh S, Gill M, Owen M, Asherson P, McGuffin P, Nanko S, Murray RM, Collier DA (1994b) Failure to find linkage between a functional polymorphism in the dopamine D4 receptor gene and schizophrenia. Am J Med Genet 54:8–11Google Scholar
  91. Sherrington R, Kalsi G, Mankoo BS, Brynjolfsson J, Curtis D, Moloney E, Rifkin L, Petursson H, Gurling HMD (1993) A linkage study with the D5 dopamine receptor in Icelandic pedigrees with multiple cases of manic depression. Psychiatr Genet 3:241–245Google Scholar
  92. Sobell J, Sigurdson DC, Heston L, Sommer S (1994) S311C D2DR variant: no association with schizophrenia. Lancet 344: 621–622Google Scholar
  93. Sobell JL, Lind TJ, Sigurdson DC, Zald DH, Snitz BE, Grove WM, Heston LL, Sommer SS (1995) The D5 dopamine receptor gene in schizophrenia: identification of a nonsense change and multiple missense changes but lack of association with disease. Hum Mol Genet 4:507–514Google Scholar
  94. Sommer SS, Lind TJ, Heston LL, Sobell JL (1993) Dopamine D4 receptor variants in unrelated schizophrenic cases and controls. Am J Med Genet 48:90–93Google Scholar
  95. Straub RE, MacLean CJ, O'Neill FA, Burke J, Murphy B, Duke F, Shikwin R, Webb BT, Zhang J, Walsh D, Kendler KS (1995) A potential vulnerability locus for schizophrenia on chromosome 6p24-22: evidence for genetic heterogeneity. Nature Genet 11: 287–293Google Scholar
  96. Su Y, Burke J, O'Neill A, Murphy B, Nie L, Kipps B, Bray J, Shinkwin R, Nuallain MN, MacLean CJ, Walsh D, Diehl SR, Kendler KS (1993) Exclusion of linkage between schizophrenia and the D2 dopamine receptor gene region of chromosome 11q in 112 Irish multiplex families. Arch Gen Psychiatry 50: 205–211Google Scholar
  97. Tanaka T, Igarashi S, Onodera O, Tanaka S, Kameda K, Takahashi K, Tsuji S, Ihda S (1995) Lack of association between dopamine D4 receptor gene and schizophrenia. Am J Med Genet 60: 580–582Google Scholar
  98. Vallada H, Curtis D, Sham PC, Murray RM, McGuffin P, Nanko S, Gill M, Owen M, Collier DA (1995a) Chromosome 22 markers demonstrate transmission disequilibrium with schizophrenia. Psychiatr Genet 5:127–130Google Scholar
  99. Vallada HP, Gill M, Sham P, Lim LCC, Nanko S, Asherson P, Murray RM, McGuffin P, Owen M, Collier D (1995b) Linkage studies on chromosome 22 in familial schizophrenia. Am J Med Genet 60:139–146Google Scholar
  100. Van Tol HHM, Bunzow JR, Guan H-C, Sunahara RK, Seeman P, Niznik HB, Civelli O (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 350:610–614Google Scholar
  101. Wang S, Cun C-E, Walczak CA, Ziegle JS, Kipps BR, Goldin LR, Diehl SR (1995) Evidence for a susceptibility locus for schizophrenia on chromosome 6pter-p22. Nature Genet 10:41–46Google Scholar
  102. Wang ZW, Black D, Andreasen NC, Crowe RR (1993) A linkage study of chromosome 11q in schizophrenia. Arch Gen Psychiatry 50:212–216Google Scholar
  103. Wei J, Ramchand CN, Hemmings GP (1995) Association of polymorphic VNTR region in the first intron of the human TH gene with disturbances of the catecholamine pathway in schizophrenia. Psychiatr Genet 5:83–88Google Scholar
  104. Wiese C, Lannfelt L, Kristbjarnarson H, Yang L, Zoega T, Sokoloff P, Ivarsson O, Schwartz J-C, Moises HW, Helgasson T (1993) No evidence of linkage between schizophrenia and D3 dopamine receptor gene locus in Icelandic pedigrees. Psychiatry Res 46:69–78Google Scholar
  105. Wong DF, Wagner HN Jr, Tune LE, Dannals RF, Pearlson GD, Links JM, Tamminga CA, Broussolle EP, Ravert HT, Wilson AA, Toung JKT, Malat J, Williams JA, O'Tuama LA, Snyder SH, Kuhar MJ, Gjedde A (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234:1558–1563Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • E. Jönsson
    • 1
  • S. Brené
    • 1
  • Th. Geijer
    • 1
  • L. Terenius
    • 1
  • A. Tylec
    • 1
  • M. -L. Persson
    • 2
    • 3
  • G. Sedvall
    • 1
  1. 1.Department of Clinical NeuroscienceKarolinska InstituteStockholmSweden
  2. 2.Department of Clinical Neuroscience and Family Medicine, Section of PsychiatryKarolinska InstituteStockholmSweden
  3. 3.National Institute for Psychosocial Factors and Health, Karolinska InstituteNational and Stockholm County Council Centre for Suicide Research and PreventionStockholmSweden

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