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Molecular Genetics and Heterogeneity in Manic Depression

  • H. M. D. Gurling
  • R. P. Sherrington
  • J. Brynjolfsson
  • M. Potter
  • M. Mclnnis
  • H. Petursson
  • S. Hodgkinson
Part of the Molecular Neurobiology · 1988 · book series (MN)

Abstract

Recent research has shown that there are X-linked and possibly chromosome 11-linked forms of manic depression as well as at least one other autosomal form. Segregation analyses of large affected families and the finding of genetic linkage between chromosome specific markers and manic depression mutations provide strong evidence that bipolar as well as unipolar forms of manic depression (MD) within the same family are inherited as a dominant gene disorder. This clarification of the etiology of certain types of depression should bring changed attitudes within psychiatry and may serve to stimulate discusssion of the role of evolutionary mechanisms. From a clinical point of view, it has now become possible to determine whether clinical (phenotypic) variation reflects the underlying genotypic heterogeneity of linkage. A preliminary analysis of data from four recent studies shows that there is no clear correlation between such clinical features as the ratio of unipolar to bipolar cases and the genotypic form of manic depression. Further recombinant DNA research, proven to be successful in other genetic diseases, can soon be applied to manic depression. The specific problems posed by manic depression for these techniques are discussed.

Index Entries

Manic depression heterogeneity genotypic X-llinkage chromosome 11-linkage variation, phenotypic 

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References

  1. Baron M., Risch N., Hamburger R., Mandel B., Kushner S., Newman M., Drumer D., and Belmaker R. H. (1987) X chromosome markers and bipolar affective illness. Nature 326, 289–292.PubMedCrossRefGoogle Scholar
  2. Bryant E. H. (1986) The effect of an experimental bottleneck upon quanititative genetic variation in the housefly. Genetics 114, 1191–1197.PubMedGoogle Scholar
  3. Detera Wadleigh S. D., Berritini W. H., Goldin L. R., Boorman D., Anderson G., and Gershon E. S. (1987) Close linkage of C Harvey-ras 1 and the insulin gene to affective disorder is ruled out in three North American pegigrees. Nature 325, 783–787.CrossRefGoogle Scholar
  4. Dewar A. J. and Reading H. W. (1971) Effect of Lithium administration on RNA metabolism in rat brain. Psychological Medicine 1, 254–259.PubMedCrossRefGoogle Scholar
  5. Egeland J., Gerhard D. S., Pauls D. L., Sussex J. N., Kidd K., Allen C. R., Hostetter A. M., and Housman D. E. (1987) Bipolar affective disorders linked to DNA markers on chromosome 11. Nature 325, 783–787.PubMedCrossRefGoogle Scholar
  6. Estivill X., Farrall M., Scambler P. J., Bell G. M., Hawley K. M. F., Lench N. J., Bates G. P., Kruyer, H. C., Frederich P. A., Stanier P., Watson E. K., Williamson R., Wainright B. J. (1987) A candidate for the cystic fibrosis locus isolated by selection for methylation-free islands. Nature 326, 840–845.PubMedCrossRefGoogle Scholar
  7. Francke U., Ochs H. D., De Martinville B., Giacalone J., Lindgren V., Distech V., Pagan R. A., Hofker M. H., Van Ommen G. K. S., Pearson P. L., and Wedgewood R. J. (1985) Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulo-matous disease, retinitis pigmentosa and McLeod Syndrome. Am J. Hum. Genet. 37, 250–267.PubMedGoogle Scholar
  8. Gershon E. S., Hamovit J. H., Guroff J. J., and Nurnberger J. I. (1987) Birth-cohort changes in manic and depressive disorders in relatives of bipolar-and schizoaffective patients. Arch. Gen. Psychiat. 44, 314–319.PubMedGoogle Scholar
  9. Gill M. (1988) Unpublished work. Accepted for publication in the Journal of Medical Genetics, in pressGoogle Scholar
  10. Hodgkinson S., Curling H. M. D., Marchbanks R. M., McInnis M., and Petursson H. (1987) Minisatellite mapping in manic depression. J. Psychiat. Research 21, 589–596.CrossRefGoogle Scholar
  11. Hodgkinson S., Sherrington R., Curling H. M. D., Marchbanks R. M., Reeders S. T., Mallet J., Petursson, H., and Brynjolfsson J. (1987) Molecular genetic evidence for heterogeneity in manic depression. Nature 325, 805–806.PubMedCrossRefGoogle Scholar
  12. Jeffreys A. J., Wilson V., and Thein S. L. (1985) Hypervariable “minisatellite” regions in human DNA. Nature 314, 67–73.PubMedCrossRefGoogle Scholar
  13. Kunkel K. M., Monaco A. P., Middlesworth W., Ochs H. D., and Latt S. A. (1985) Specific cloning of DNA fragments absent from the DNA of a male patient with an X chromosome deletion. Proc. Natl. Acad. Sci. USA 82, 4778–4782.PubMedCrossRefGoogle Scholar
  14. Mendelwicz J., Simon P., Sevy S., Charon F., Brocas H., Legros S., and Vassart G. (1987) Polymorphic Marker on X chromosome and manic depression. Lancet 8544, 1230–1231.CrossRefGoogle Scholar
  15. Monaco A. P., Bertelson W., Middlesworth W., Collett C. A., Aldridge J., Fishbeck R., Bartlett R., Pericak-Vance M. A., Roses A. D., and Kunkel, L. M. (1985) Detection of deletions spanning Duchenne Muscular Dystrophy locus using a tightly linked DNA segment. Nature 316, 842–845.PubMedCrossRefGoogle Scholar
  16. Nakamura Y., Leppert M., O’Connel P., Wolff R., Holm T., Culvier M., Martin C., Fujimoto E., Hoff M., Kumlin E., and White R. (1987) Variable number of tandem repeat (VNTR) markers for human gene mapping. Science 235, 1616–1622.PubMedCrossRefGoogle Scholar
  17. Pauls D. (1985) Segregation analysis of Bipolar and Unipolar disorders in the US Amish. Fourth World Congress in Biological Psychiatry, Philadelphia, USA.Google Scholar
  18. Reich T., Clayton P. J., and Winokur G. (1960) Family history studies. V: The genetics of Mania. Am. J. Psychiat. 125, 1358–1369.Google Scholar
  19. Royer-Pokora B., Kunkel L. M., Monaco A. P., Goff S. C., Newburger P. E., Baehner R. L., Sessions Cole F. S., Curnutte J. T., and Orkin S. H. (1986) Cloning the gene for an inherited human disorder—chronic granulomatous disease on the basis of its chromosomal location. Nature 322, 32–38.PubMedCrossRefGoogle Scholar
  20. Spitzer R. L. and Endicott J. (1978) Critical Issues in Psychiatric Diagnoses, Raven, New York.Google Scholar

Copyright information

© The Humana Press Inc. 1989

Authors and Affiliations

  • H. M. D. Gurling
    • 1
  • R. P. Sherrington
    • 1
  • J. Brynjolfsson
    • 2
  • M. Potter
    • 1
  • M. Mclnnis
    • 2
  • H. Petursson
    • 2
  • S. Hodgkinson
    • 1
  1. 1.Molecular Psychiatry Laboratory, Academic Department of PsychiatryUniversity College and Middlesex School of Medicine, University of LondonLondonUK
  2. 2.Department of PsychiatryBorgaspitalinnReykjavikIceland

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