Hostname: page-component-848d4c4894-nmvwc Total loading time: 0 Render date: 2024-07-01T01:20:11.628Z Has data issue: false hasContentIssue false

Genetics of bipolar disorders

Published online by Cambridge University Press:  18 September 2015

D. Souery*
Affiliation:
Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Brussels, Belgium
I. Massat
Affiliation:
Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Brussels, Belgium
J. Mendlewicz
Affiliation:
Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Brussels, Belgium
*
Department of Psychiatry, University Clinics of Brussels Erasme Hospital, 808 Route de Lennik, 1070 Brussels, Belgium Fax 32-2-5554515E-mail, [email protected]

Abstract

Advances towards the understanding of the etiological mechanisms involved in mood disorders provide interesting yet diverse hypotheses and promising models. In this context, molecular genetics has now been widely incorporated into genetic epidemiological research in psychiatry. Affective disorders and, in particular, bipolar affective disorder (BPAD) have been examined in many molecular genetic studies which have covered a large part of the genome, specific hypotheses such as mutations have also been studied. Most recent studies indicate that several chromosomal regions may be involved in the aetiology of BPAD. Other studies have reported the presence of anticipation in BPAD. This phenomenon describes the increase in clinical severity and decrease in age of onset observed in successive generations. This mode of transmission correlates with the presence of specific mutations (Trinucleotide Repeat Sequences) and may represent a genetic factor involved in the transmission of the disorder. In parallel to these new developments in molecular genetics, the classical genetic epidemiology, represented by twin, adoption and family studies, provided additional evidence in favour of the genetic hypothesis in mood disorders. Moreover, these methods have been improved through models to test the gene-environment interactions. While significant advances have been made in this major field of research, it appears that integrative models, taking into account the interactions between biological (genetic) factors and social (psychosocial environment) variables offer the most reliable way to approach the complex mechanisms involved in the etiology and outcome of mood disorders.

Type
Articles
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2000

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.McInnis, MG. McMahon, FJ. Chase, GAet al.Anticipation in bipolar affective disorder. Am J Hum Genet 1993:53:385390.Google ScholarPubMed
2.Nylander, P-O. Engstrom, C. Chotai, J. Wahlström, J. Adolfsson, R. Anticipation in Swedish Families with Bipolar Affective Disorder. J Med Genet 1994;9:686689.CrossRefGoogle Scholar
3.Lindblad, K. Nylander, PO. De Bruyn, A. et al.Expansion of trinucleotide CAG repeats detected in Bipolar Affective Disorder by the RED-(rapid expansion detection) method. Neurobiol Dis 1995:2:5562.CrossRefGoogle Scholar
4.Weiss, KM. Genetic variation and human disease: principles and evolutionary approaches. Cambridge. Cambridge University Press. 1993, pp.117148.CrossRefGoogle Scholar
5.Ott, J. Analysis of Human Genetic Linkage. Second edition. Baltimore. Johns Hopkins University Press. 1991.Google Scholar
6.Propping, P. Nothen, MM. Fimmers, Ret al.Linkage versus association studies in complex diseases. Pychiatr Gen 1993:3:136142.Google Scholar
7.Hodge, SE. Linkage analysis versus association analysis: distinguishing between two models that explain disease-marker associations. Am J Med Gen 1993:53:367384.Google ScholarPubMed
8.Terwilliger, JD. Ott, J. A haplotype-based haplotype relative risk statistic. Hum Heredity 1992:42:337346.CrossRefGoogle Scholar
9.Hodge, SE. What association analysis can and cannot tell us about the genetics of complex disease. Am J Med Gen 1994:54:318323.CrossRefGoogle ScholarPubMed
10.Berrettini, WH. Ferraro, TN. Goldin, LRet al.Chromosome 18 DNA markers and manic-depressive illness : Evidence for a susceptibility gene. Proc Nat Acad Sci USA 1994:91:59185922.CrossRefGoogle ScholarPubMed
11.Souery, D, Papadimitriou, G. Mendlewicz, J. New genetic approaches in affective disorders. In: Papadimitriou, GN.. Mendlewicz, J. (eds.). Genetics of Mental Disorders Part I: Theoretical aspects. London. Baillière's Clinical Psychiatry. International Practice and Research. Baillière Tindall. 1996. pp 97110.Google Scholar
12.Barden, N. Plante, M. Rochette, D. Gagne, Bet al.Genome wide microsatellite marker linkage study of bipolar affective disorders in a very large pedigree derived from a homogeneous population in Quebec points to susceptibility locus on chromosome 12. Psychiatr Gen 1996:6:145146.CrossRefGoogle Scholar
13.Ewald, H. Degn, B. Mors, O. Kruse, TA. Significant linkage between bipolar affective disorder and chromosome 12q24. Psychiatr Gen 1998:8:131140.CrossRefGoogle ScholarPubMed
14.Franks, E, Guy, C. Jacobsen, N. Bowen, T. Owen, MJet al.Eleven trinucleotide repeat loci that map to chromosome 12 excluded from involvement in the pathogenesis of bipolar disorder. Am J Med Gen 1999;5:6770.3.0.CO;2-#>CrossRefGoogle Scholar
15.Mendlewicz, J. Simon, P. Sevy, Set al.Polymorphic DNA marker on chromosome and manic-depression. Lancet 1987:1:12301232.CrossRefGoogle ScholarPubMed
16.Pekkarinen, P. Terwilliger, J. Bredbacka, P-E. Lonnqvist, J. Peltonen, L. Evidence of a predisposing locus to bipolar disorder on Xq24-q27.1 in an extended Finnish pedigree. Genome Res 1995:5:105115.CrossRefGoogle Scholar
17.Ogilvie, AD. Battersby, S. Bubb, VJet al.Polymorphism in serotonin transporter gene associated with susceptibility to major depression. Lancet 1996:347:731733.CrossRefGoogle ScholarPubMed
18.Gutierrez, B. Pintor, L. Gasto, C. Rosa, A. et al.Variability in the serotonin transporter gene and increased risk for major depression with melancholia. Hum Gen 1998:103:319–22.CrossRefGoogle ScholarPubMed
19.Gutierrez, B. Arranz, MJ. Collier, DA. Valles, V. et al.Serotonin transporter gene and risk for bipolar affective disorder: an association study in Spanish population. Biol Psychiatry 1998:43:843847.CrossRefGoogle ScholarPubMed
20.Smeraldi, E. Zanardi, R. Benedetti, F. Di Bella, Det al.Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Mol Psychiatry 1998:3:508511.CrossRefGoogle ScholarPubMed
21.Bcllivier, F. Leboyer, M. Courtet, P. Buresi, Cet al.Association between the tryptophan hydroxylase gene and manie-depressive illness. Arch Gen Psychiatry 1998:55:3337.CrossRefGoogle Scholar
22.Mann, JJ. Malone, KM, Nielsen, DA, Goldman, et al.Possible association of a polymorphism of the tryptophan hydroxylase gene with suicidal behavior in depressed patients. Am J Psychiatry 1997: 154:14511453.Google ScholarPubMed
23.Blackwood, D. He, L. Morris, Set al.A locus for bipolar affective disorder on chromosome 4p. Nature Genetics 1996:12:427430.CrossRefGoogle ScholarPubMed
24.Straub, RE, Lehner, Th, Luo, Yet al.A possible vulnerability locus for bipolar affective disorder on chromosome 21q22.3. Nature Gen 1994;8:291296.CrossRefGoogle ScholarPubMed
25.Mendlewicz, J, Lipp, O. Souery, Det al.Possible maternal genomic imprinting on expended trinucleotide CAG repeats in bipolar affective disorder. Biol Psychiatry 1997:42:11151122.CrossRefGoogle Scholar
26.Lindblad, K, Nylander, P-O. Zander, C. Yuan, Q-Pet al.Two commonly expanded CAG/CTG repeat loci: involvmcnt in affective disorders? Mol Psychiatry 1998,2.Google Scholar
27.Kendler, KS. Major depression and the environment: a psychiatric genetic perspective. Pharmacopsychiatry 1998:31-59.CrossRefGoogle ScholarPubMed