Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Research Article
  • Published:

Lack of evidence to support the association of the human prion gene with schizophrenia

Abstract

Recently a new variant of Creutzfeldt–Jakob disease, a human prion disease, with prominent psychiatric manifestations in the early stage was identified, suggesting that human prion disease may be associated with mental disorders. Furthermore, a novel missense mutation with asparagine-to-serine substitution at codon 171 of the human prion gene (N171S) was identified in a family with severe psychiatric symptoms. This finding provides further clue that the prion gene may be a susceptibility gene for certain psychiatric disorders. We systematically sequenced the protein-coding and untranslated exons of prion gene in 62 Han Chinese schizophrenic patients with positive family history from Taiwan. We identified two polymorphisms that alter amino acid sequences, a methionine/valine at codon 129 (M129V) and a glutamate/lysine at codon 219 (E219K), respectively. Further comparison of the genotype, allele and haplotype frequency distributions of these two polymorphisms between 234 schizophrenic patients and 100 non-psychotic controls, however, did not reveal significant differences between two groups. Besides, no other mutations in the prion gene were identified in these 62 patients. Hence, our results suggest that the prion gene may not play a major role in conferring susceptibility to schizophrenia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Collinge J . Human prion disease and bovine spongiform encephalopathy (BSE) Hum Mol Genet 1997 6: 1699–1705

    Article  CAS  Google Scholar 

  2. Weissmann C . Molecular biology of transmissible spongiform encephalopathies FEBS Lett 1996 389: 3–11

    Article  CAS  Google Scholar 

  3. Goldfarb LG, Brown P, Cervenakova L, Gajdusek DC . Molecular genetic studies of Creutzfeldt–Jakob disease Mol Neurobiol 1994 8: 89–97

    Article  CAS  Google Scholar 

  4. Collinge J, Rossor M . A new variant of prion disease Lancet 1996 347: 916–917

    Article  CAS  Google Scholar 

  5. Will RG, Matthews WB . A retrospective study of Creutzfeldt–Jakob disease in England and Wales 1970–1979. I: Clinical features J Neurol Neurosurg Psychiatry 1984 47: 134–140

    Article  CAS  Google Scholar 

  6. Brown P, Cathala F, Sadowsky D, Gajdusek DC . Creutzfeldt–Jakob disease in France III. Clinical characteristics of 124 consecutive verified cases during the decade 1968–1977 Ann Neurol 1979 6: 430–437

    Article  CAS  Google Scholar 

  7. Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A et al. A new variant of Creutzfeldt–Jakob disease in the UK Lancet 1996 347: 921–925

    Article  CAS  Google Scholar 

  8. Zeidler M, Johnstone EC, Bamber RWK, Dickens CM, Fisher CJ, Francis AF et al. New variant Creutzfeldt–Jakob disease: psychiatric features Lancet 1997 350: 908–910

    Article  CAS  Google Scholar 

  9. Harrison PJ . BSE and human prion disease Br J Psychiatry 1997 170: 298–300

    Article  CAS  Google Scholar 

  10. Samaia HB, de Jesus Mari J, Vallada HP, Moura RP, Simpson AJG, Brentani RR . A prion-linked psychiatric disorder Nature 1997 390: 241

    Article  CAS  Google Scholar 

  11. Sparkes RS, Simon M, Cohn VH, Fournier REK, Lem J, Klisak I et al. Assignment of the human and mouse prion protein genes to homologous chromosomes Proc Natl Acad Sci USA 1986 83: 7358–7362

    Article  CAS  Google Scholar 

  12. Lee IY, Westaway D, Smit AFA, Wang K, Seto J, Chen L et al. Complete genomic sequence and analysis of the prion protein gene region from three mammalian species Genome Res 1998 8: 1022–1037

    Article  CAS  Google Scholar 

  13. Palmer MS, Dryden AJ, Hughes JT, Collinge J . Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob disease Nature 1991 352: 340–341

    Article  CAS  Google Scholar 

  14. Furukawa H, Kitamoto T, Tanaka Y, Tateishi J . New variant prion protein in a Japanese family with Gerstmann–Strauessler syndrome Mol Brain Res 1995 30: 385–388

    Article  CAS  Google Scholar 

  15. Schneider S, Kueffer J-M, Roessli D, Excoffer I . Arlequin, Version 1.1: a software for population genetic data analysis Genetics and Biometry Laboratory, University of Geneva 1997

    Google Scholar 

  16. Ott J . Analysis of Human Genetic Linkage, rev edn Johns Hopkins University Press: Baltimore 1991

    Google Scholar 

  17. Keshavan MS, Lishman WA, Haghes JT . Psychiatric presentation of Creutzfeldt–Jakob disease. A case report Br J Psychiatry 1987 151: 260–263

    Article  CAS  Google Scholar 

  18. Azorin JM, Donnet A, Dassa D et al. Creutzfeldt–Jakob disease misdiagnosed as depressive pseudodementia Compr Psychiatry 1993 34: 42–44

    Article  CAS  Google Scholar 

  19. Stevens EM, Lament R . Psychiatric presentation of Creutzfeldt–Jakob disease J Clin Psychiatry 1979 40: 445–446

    CAS  PubMed  Google Scholar 

  20. Yen CF, Lin RT, Liu CK, Lee PW, Hen CC, Chang YP . The psychiatric manifestation of Creutzfeldt–Jakob disease Kao Hsiung I Hsueh Ko Hsueh Tsa Chih 1997 13: 263–267

    CAS  Google Scholar 

  21. Snow RE, Arnold SE . Psychosis in neurodegenerative disease Semin Clin Neuropsychiatry 1996 1: 282–293

    CAS  PubMed  Google Scholar 

  22. Palmer M, Collinge J . Mutations and polymorphisms in the prion protein gene Hum Mut 1993 2: 168–173

    Article  CAS  Google Scholar 

  23. Prusiner SR, Scott MR, DeArmond SJ, Cohen FE . Prion protein biology Cell 1998 93: 337–348

    Article  CAS  Google Scholar 

  24. Arnold SE, Trojanowski JQ, Parchi P . Protease resistant prion proteins are not present in sporadic ‘poor outcome’ schizophrenia J Neurol Neurosurg Psychiatry 1999 66: 90–92

    Article  CAS  Google Scholar 

  25. Collinge J, Palmer MS, Dryden AJ . Genetics predisposition to iatrogenic Creutzfeldt–Jakob disease Lancet 1991 337: 1441–1442

    Article  CAS  Google Scholar 

  26. Goldfarb LG, Petersen RB, Tabaton M, Brown P, LeBlanc AC, Montagna P et al. Fatal familial insomnia and familial CJD: disease phenotype determined by a DNA polymorphism Science 1992 258: 806–808

    Article  CAS  Google Scholar 

  27. Kitamoto T, Tateishi J . Human prion disease with variant protein Philos Trans R Soc Lond B Biol Sci 1994 343: 391–398

    Article  CAS  Google Scholar 

  28. Shibuya S, Higuchi J, Shin R-W, Tateishi J, Kitamoto T . Protective prion protein polymorphisms against sporadic Creutzfeldt–Jakob disease Lancet 1998 351: 419

    Article  CAS  Google Scholar 

  29. Petraroli R, Pocchiari M . Codon 219 polymorphism of PRNP in healthy Caucasians and Creutzfeldt–Jakob disease patients Am J Hum Genet 1996 58: 888–889

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The study was supported by grant NSC-88-2314-B-320-023 from the National Science Council, Taiwan, ROC.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C-H Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsai, MT., Su, YC., Chen, YH. et al. Lack of evidence to support the association of the human prion gene with schizophrenia. Mol Psychiatry 6, 74–78 (2001). https://doi.org/10.1038/sj.mp.4000790

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4000790

Keywords

This article is cited by

Search

Quick links