Molecular Genetic Studies in Affective Disorders

  • M. Baron
Conference paper

Abstract

Evidence for substantial genetic contribution to bipolar and related affective disorders is provided by family, twin, and adoption studies. However, uncertainties concerning the mode of genetic transmission, etiologic heterogeneity, and phenotypic boundaries compromise the prospects of unraveling the underlying genetic defect. Molecular genetic techniques, including recombinant DNA technology, will likely have a key role in resolving some of these issues. The implications of these advances for affective disorder research are discussed here in the light of recent genetic findings linking bipolar affective illness to gene markers on chromosome 11 and the X chromosome. The topics covered include the principles and promise of the recombinant DNA approach and other molecular biology techniques; the limitations in studying disorders typified by nosological uncertainties, unknown mode of inheritance, and etiologic heterogeneity; and the potential contribution of molecular genetic strategies to the elucidation of genotypic variation.

Keywords

Depression Lithium Dopamine Tyrosine Recombination 

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References

  1. Baron M (1989) Molecular biology of neuroreceptors: implications for clinical neuroscience. In: Maelicke A (ed) Molecular biology of neuroreceptors and ion channels, NATO ASI series. Springer, Berlin Heidelberg New York, pp 643–659Google Scholar
  2. Baron M, Rainer JD (1988) Molecular genetics and human disease: implications for modern psychiatric research and practice. Br J Psychiatry 152: 741–753PubMedCrossRefGoogle Scholar
  3. Baron M, Rainer JD, Risch N (1981) Linkage in bipolar affective illness: perspectives on genetic heterogeneity, pedigree analysis and the X-chromosome map. J Affective Disord 3: 141–157CrossRefGoogle Scholar
  4. Baron M, Risch N, Hamburger R, Mandel B, Kushner S, Newman M, Drumer D, Belmaker RH (1987) Genetic linkage between X-chromosome markers and bipolar affective illness. Nature 326: 289–292PubMedCrossRefGoogle Scholar
  5. Davies KE, Mandel JL, Weissenbach J, Fellous M (1987) Report of the committee on the genetic constitution of the X and Y chromosome (Human Gene Mapping 9). Cytogenet Cell Genet 46 (no. l-4): 277–315PubMedCrossRefGoogle Scholar
  6. Detera-Wadleigh SD, Berrettini WH, Goldin LR, Boorman DG, Anderson S, Gershon ES (1987) Close linkage of C-Harvey-ras-1 and the insulin gene to affective disorder is ruled out in three North American pedigrees. Nature 325: 806–808PubMedCrossRefGoogle Scholar
  7. Egeland JA, Gerhard DS, Pauls DL, Sussex JN, Kidd KK, Allen CR, Hostetter AM, Housman D (1987) Bipolar affective disorder linked to DNA markers on chromosome 11. Nature 325: 783–787PubMedCrossRefGoogle Scholar
  8. Gurling HMD (1985) Application of molecular biology to mental illness. Analysis of genomic DNA and brain mRNA. Psychiatr Dev 3: 257–273PubMedGoogle Scholar
  9. Gurling HMD (1986) Candidate genes and favored loci: strategies for molecular genetic research into schizophrenia, manic depression, autism, alcoholism and Alzheimer’s disease. Psychiatr Dev 4: 289–309PubMedGoogle Scholar
  10. Hodkinson S, Sherrington R, Gurling H et al. (1987) Molecular genetic evidence for heterogeneity in manic depression. Nature 325: 805–806CrossRefGoogle Scholar
  11. Mendlewicz J, Simon P, Sevy S, Charon F, Brocas H, Legros S, Vassart G (1987) Polymorphic DNA markers on X chromosome and manic depression. Lancet 2: 1230–1232CrossRefGoogle Scholar
  12. Pearson PL, Kidd KK, Willard HF (1987) Report of the committee on human gene mapping by recombinant DNA techniques (Human Gene Mapping 9). Cytogenet Cell Genetics 46 (no 1-4): 390–394CrossRefGoogle Scholar
  13. Risch N, Baron M (1982) X-linkage and genetic heterogeneity in bipolar-related major affective illness. Ann Hum Genet 46: 153–166PubMedCrossRefGoogle Scholar
  14. Risch N, Baron M, Mendlewicz J (1986) Assessing the role of X-linked inheritance in bipolar-related major affective illness. J Psychiatr Res 20: 275–288PubMedCrossRefGoogle Scholar
  15. Rosenberg MB, Hansen C, Breakefield XO (1985) Molecular genetic approaches to neurologic and psychiatric diseases. Prog Neurobiol 24: 95–140PubMedCrossRefGoogle Scholar
  16. White RL, Leppert M, Bishop DT, Barker D, Berkowitz J, Brown C, Callahan P, Holm T, Jerominski L (1985) Contruction of linkage maps with DNA markers for human chromosomes. Nature 313: 101–105PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • M. Baron
    • 1
    • 2
  1. 1.Division of Psychogenetics, Department of Medical GeneticsNew York State Psychiatric InstituteNew YorkUSA
  2. 2.Department of PsychiatryColumbia University College of Physicians and SurgeonsNew YorkUSA

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