Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1994 May;54(5):864–870.

Evidence for anticipation in schizophrenia.

A S Bassett 1, W G Honer 1
PMCID: PMC1918268  PMID: 8178826

Abstract

Anticipation, or increasing severity of a disorder across successive generations, is a genetic phenomenon with an identified molecular mechanism: expansion of unstable trinucleotide repeat sequences. This study examined anticipation in familial schizophrenia. Three generations of siblines from the affected side of families selected for unilineal, autosomal dominant-like inheritance of schizophrenia were studied (n = 186). Across generations more subjects were hospitalized with psychotic illness (P < .001), at progressively earlier ages (P < .0001), and with increasing severity of illness (P < .0003). The results indicate that anticipation is present in familial schizophrenia. These findings support both an active search for unstable trinucleotide repeat sequences in schizophrenia and reconsideration of the genetic model used for linkage studies in this disorder.

Full text

PDF
870

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andreasen N. C., Endicott J., Spitzer R. L., Winokur G. The family history method using diagnostic criteria. Reliability and validity. Arch Gen Psychiatry. 1977 Oct;34(10):1229–1235. doi: 10.1001/archpsyc.1977.01770220111013. [DOI] [PubMed] [Google Scholar]
  2. Bassett A. S., Collins E. J., Nuttall S. E., Honer W. G. Positive and negative symptoms in families with schizophrenia. Schizophr Res. 1993 Dec;11(1):9–19. doi: 10.1016/0920-9964(93)90033-f. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bassett A. S. Linkage analysis of schizophrenia: challenges and promise. Soc Biol. 1991 Fall-Winter;38(3-4):189–196. doi: 10.1080/19485565.1991.9988787. [DOI] [PubMed] [Google Scholar]
  4. Brook J. D., McCurrach M. E., Harley H. G., Buckler A. J., Church D., Aburatani H., Hunter K., Stanton V. P., Thirion J. P., Hudson T. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell. 1992 Feb 21;68(4):799–808. doi: 10.1016/0092-8674(92)90154-5. [DOI] [PubMed] [Google Scholar]
  5. Caskey C. T., Pizzuti A., Fu Y. H., Fenwick R. G., Jr, Nelson D. L. Triplet repeat mutations in human disease. Science. 1992 May 8;256(5058):784–789. doi: 10.1126/science.1589758. [DOI] [PubMed] [Google Scholar]
  6. Decina P., Mukherjee S., Lucas L., Linder J., Horwath E. Patterns of illness in parent-child pairs both hospitalized for either schizophrenia or a major mood disorder. Psychiatry Res. 1991 Oct;39(1):81–87. doi: 10.1016/0165-1781(91)90010-m. [DOI] [PubMed] [Google Scholar]
  7. Flint J. Implications of genomic imprinting for psychiatric genetics. Psychol Med. 1992 Feb;22(1):5–10. doi: 10.1017/s0033291700032669. [DOI] [PubMed] [Google Scholar]
  8. Fu Y. H., Pizzuti A., Fenwick R. G., Jr, King J., Rajnarayan S., Dunne P. W., Dubel J., Nasser G. A., Ashizawa T., de Jong P. An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science. 1992 Mar 6;255(5049):1256–1258. doi: 10.1126/science.1546326. [DOI] [PubMed] [Google Scholar]
  9. Gershon E. S., Hamovit J. H., Guroff J. J., Nurnberger J. I. Birth-cohort changes in manic and depressive disorders in relatives of bipolar and schizoaffective patients. Arch Gen Psychiatry. 1987 Apr;44(4):314–319. doi: 10.1001/archpsyc.1987.01800160018004. [DOI] [PubMed] [Google Scholar]
  10. Kendler K. S., Gruenberg A. M., Tsuang M. T. Psychiatric illness in first-degree relatives of schizophrenic and surgical control patients. A family study using DSM-III criteria. Arch Gen Psychiatry. 1985 Aug;42(8):770–779. doi: 10.1001/archpsyc.1985.01790310032004. [DOI] [PubMed] [Google Scholar]
  11. Lavedan C., Hofmann-Radvanyi H., Shelbourne P., Rabes J. P., Duros C., Savoy D., Dehaupas I., Luce S., Johnson K., Junien C. Myotonic dystrophy: size- and sex-dependent dynamics of CTG meiotic instability, and somatic mosaicism. Am J Hum Genet. 1993 May;52(5):875–883. [PMC free article] [PubMed] [Google Scholar]
  12. Lowing P. A., Mirsky A. F., Pereira R. The inheritance of schizophrenia spectrum disorders: a reanalysis of the Danish adoptee study data. Am J Psychiatry. 1983 Sep;140(9):1167–1171. doi: 10.1176/ajp.140.9.1167. [DOI] [PubMed] [Google Scholar]
  13. McInnis M. G., McMahon F. J., Chase G. A., Simpson S. G., Ross C. A., DePaulo J. R., Jr Anticipation in bipolar affective disorder. Am J Hum Genet. 1993 Aug;53(2):385–390. [PMC free article] [PubMed] [Google Scholar]
  14. Orr H. T., Chung M. Y., Banfi S., Kwiatkowski T. J., Jr, Servadio A., Beaudet A. L., McCall A. E., Duvick L. A., Ranum L. P., Zoghbi H. Y. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet. 1993 Jul;4(3):221–226. doi: 10.1038/ng0793-221. [DOI] [PubMed] [Google Scholar]
  15. Risch N. Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet. 1990 Feb;46(2):222–228. [PMC free article] [PubMed] [Google Scholar]
  16. Schalling M., Hudson T. J., Buetow K. H., Housman D. E. Direct detection of novel expanded trinucleotide repeats in the human genome. Nat Genet. 1993 Jun;4(2):135–139. doi: 10.1038/ng0693-135. [DOI] [PubMed] [Google Scholar]
  17. Verkerk A. J., Pieretti M., Sutcliffe J. S., Fu Y. H., Kuhl D. P., Pizzuti A., Reiner O., Richards S., Victoria M. F., Zhang F. P. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell. 1991 May 31;65(5):905–914. doi: 10.1016/0092-8674(91)90397-h. [DOI] [PubMed] [Google Scholar]
  18. Wetterberg L., Farmer A. E. Clinical polydiagnostic studies in a large Swedish pedigree with schizophrenia. Eur Arch Psychiatry Clin Neurosci. 1991;240(3):188–190. doi: 10.1007/BF02190762. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES