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The Familial Transmission of Bipolar Illness

The Familial Transmission of Bipolar Illness Abstract • As part of the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression study, data were collected on 2225 first-degree relatives of 612 probands. We analyzed 187 families of bipolar patients (149 probands with a diagnosis of bipolar I disorder and 38 with a diagnosis of schizoaffective, manic subtype). Using traditional genetic methods, the morbid risk of bipolar illness in relatives was found to be 5.7% in the relatives of bipolar probands as contrasted with 1.1% in the relatives of probands with major depression. These values compared closely with those obtained using survival analysis. Relatives of probands with early onset were found to have a greater risk than relatives of probands with late onset. The sex of the relative, the sex of the proband, or the subtype of the proband (bipolar I or schizoaffective bipolar) did not influence the risk in the relative. The age at onset was found to be accelerated with birth cohort, with individuals born in more recent cohorts having an earlier onset. Multifactorial analysis found significant heterogeneity for sex-specific sibling correlations (with the brother-sister correlation smaller than the same-sexed correlations), and path analysis estimated transmissibility of liability to be 71%. The mixed model, which allows for a single major locus with a multifactorial background, gave evidence for the presence of a major locus when controlling for the effects of birth cohort and age at onset. However, this evidence is tempered when comparing the mixed model with a more general transmission model. References 1. Katz MM, Klerman GL: Introduction: Overview of the clinical studying program . Am J Psychiatry 1979;136:49-51. 2. Andreasen NC, Rice J, Endicott J, Reich T, Coryell W, Grove WM: Familial rates of affective disorder: A report from the National Institute of Mental Health Collaborative Study . Arch Gen Psychiatry 1987;44:461-469.Crossref 3. Morton NE, Chung CS: Genetic Epidemiology . Orlando, Fla, Academic Press Inc, 1978. 4. Sing C, Skolnick M: Genetic Analysis of Common Diseases: Applications to Predictive Factors in Coronary Diseases . New York, Alan R. Liss Inc, 1979. 5. Elandt-Johnson RC: Probability Models and Statistical Methods in Genetics . New York, John Wiley & Sons Inc, 1971. 6. Boyd JH, Weissman MM: Epidemiology of affective disorders: A reexamination and future directions . Arch Gen Psychiatry 1981;38:1039-1046.Crossref 7. Perris C: A study of bipolar (manic-depressives) and unipolar recurrent affective psychoses . Acta Psychiatr Scand 1966;42( (suppl 194) ):1-189.Crossref 8. Angst J: Zur ätiologie und Nosologie Endogener Depressiver Psychosen . Monogr Gesamtgeb Psychiatr 1966;112:1-118. 9. Gershon E, Mark A, Cohen N, Belizon N, Baron M, Knobe K: Transmitted factors in the morbid risk of affective disorders: A controlled study . J Psychiatr Res 1975;12:283-299.Crossref 10. Smeraldi E, Negri F, Melian AM: A genetic study of affective disorders . Acta Psychiatr Scand 1977;56:382-398.Crossref 11. Taylor MA, Abrams R, Hayman MA: The classification of affective disorders: A reassessment of the bipolar-unipolar dichotomy . J Affective Disord 1980;2:95-109.Crossref 12. Gershon ES, Hamovit S, Guroff JJ, Dibble E, Leckman JF, Sceery W, Targum SD, Nurnberger JI, Goldin LR, Bunney WE: A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands . Arch Gen Psychiatry 1982;39:1157-1167.Crossref 13. Winokur G, Tsuang MT, Crowe RR: The Iowa 500: Affective disorder in relatives of manic and depressed patients . Am J Psychiatry 1982;139:209-212. 14. Klerman GL, Lavori PW, Rice J: Birth cohort trends in rates of major depressive disorder among relatives of patients with affective disorder . Arch Gen Psychiatry 1985;42:689-693.Crossref 15. Spitzer RL, Endicott J, Robins E: Research Diagnostic Criteria (RDC)for a Selected Group of Functional Disorders . New York, New York State Psychiatric Institute, 1975. 16. Endicott J, Spitzer RL: A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia . Arch Gen Psychiatry 1978;35:837-844.Crossref 17. Strögren E: Zum Ersatz des Weinberg' schen 'abgekürzten Ver fahrens': Zugleich ein Beitrag zur Frage von der Erblichkeit des Erkrankungsalters bei der Schizophrenie . Zentralbl Ges Neurol Psychiatr 1935;153:764-797. 18. Kalbfleish JD, Prentice RL: The Statistical Analysis of Failure Time Data . New York, John Wiley & Sons Inc, 1980. 19. Preston DL, Clarkson DB: SURVREG: A program for the interactive analysis of survival regression analysis . Am Statistician 1983;37:174.Crossref 20. Morton NE, Rao DC, Lalouel J: Methods in Genetic Epidemiology . New York, S Karger AG, 1982. 21. Rice J, Reich T: Familial analysis of qualitative traits under multifactorial inheritance . Genet Epidemiol 1985;2:301-315.Crossref 22. Rice J, Cloninger CR, Reich T: General causal models for sex differences in the familial transmission of multifactorial traits: An application to human spatial visualizing ability . Soc Biol 1980;27:36-47. 23. Rice J, Nichols P, Gottesman II: Assessment of sex differences for qualitative multifactorial traits using path analysis . Psychiatry Res 1981;4:301-312.Crossref 24. Lalouel JM, Morton NE: Complex segregation analysis with pointers . Hum Hered 1981;31:312-321.Crossref 25. Lalouel JM, Rao DC, Morton NE, Elston RC: A unified model for complex segregation analysis . Am J Hum Genet 1983;35:816-826. 26. Elston RC, Yelverton KC: General models for segregation analysis . Am J Hum Genet 1975;27:31-45. 27. Robins LN, Helzer JE, Weissman MM, Orvaschel H, Gruenberg E, Burke JD, Regier D: Lifetime prevalence of specific psychiatric disorders in three sites . Arch Gen Psychiatry 1984;41:949-958.Crossref 28. Rice J, Cloninger CR, Reich T: Multifactorial inheritance with cultural transmission and assortative mating: I. Description and basic properties of the unitary models . Am J Hum Genet 1978;30:618-643. 29. Andreasen NC, Rice J, Endicott J, Reich T, Coryell W: The family history approach to diagnosis: How useful is it? Arch Gen Psychiatry 1986;43:421-429.Crossref 30. Lavori PW, Klerman GL, Keller MB, Reich T, Rice J, Endicott J: Ageperiod-cohort analysis of secular trends in onset of major depression: Findings in siblings of patients with major affective disorder . J Psychiatr Res , in press. 31. Weissman M, Myers J: Affective disorders in a United States urban community: The use of Research Diagnostic Criteria in an epidemiologic survey . Arch Gen Psychiatry 1978;35:1304-1311.Crossref 32. Hagnell 0, Lanke J, Rorsman B, Ojesjo L: Are we entering an age of melancholy? Depressive illnesses in a prospective epidemiological study over 25 years: Lundby study, Sweden . Psychol Med 1982;12:122-129. 33. Gershon ES, Hamovit JH, Guroff JJ, Nurnberger JI: Birth-cohort changes in manic and depressive disorders in relatives of bipolar and schizoaffective patients . Arch Gen Psychiatry 1987;44:314-319.Crossref 34. Weissman MM, Kidd KK, Prusoff BP: Variability in rates of affective disorders in relatives of depressed and normal probands . Arch Gen Psychiatry 1982;39:1397-1403.Crossref 35. Rice J, Reich T, Andreasen NC, Lavori PW, Endicott J, Clayton PJ, Keller MB, Hirschfeld RMA, Klerman GL: Sex related differences in depression: Familial evidence . J Affective Disord 1984;7:199-210.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

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References (41)

Publisher
American Medical Association
Copyright
Copyright © 1987 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1987.01800170063009
Publisher site
See Article on Publisher Site

Abstract

Abstract • As part of the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression study, data were collected on 2225 first-degree relatives of 612 probands. We analyzed 187 families of bipolar patients (149 probands with a diagnosis of bipolar I disorder and 38 with a diagnosis of schizoaffective, manic subtype). Using traditional genetic methods, the morbid risk of bipolar illness in relatives was found to be 5.7% in the relatives of bipolar probands as contrasted with 1.1% in the relatives of probands with major depression. These values compared closely with those obtained using survival analysis. Relatives of probands with early onset were found to have a greater risk than relatives of probands with late onset. The sex of the relative, the sex of the proband, or the subtype of the proband (bipolar I or schizoaffective bipolar) did not influence the risk in the relative. The age at onset was found to be accelerated with birth cohort, with individuals born in more recent cohorts having an earlier onset. Multifactorial analysis found significant heterogeneity for sex-specific sibling correlations (with the brother-sister correlation smaller than the same-sexed correlations), and path analysis estimated transmissibility of liability to be 71%. The mixed model, which allows for a single major locus with a multifactorial background, gave evidence for the presence of a major locus when controlling for the effects of birth cohort and age at onset. However, this evidence is tempered when comparing the mixed model with a more general transmission model. References 1. Katz MM, Klerman GL: Introduction: Overview of the clinical studying program . Am J Psychiatry 1979;136:49-51. 2. Andreasen NC, Rice J, Endicott J, Reich T, Coryell W, Grove WM: Familial rates of affective disorder: A report from the National Institute of Mental Health Collaborative Study . Arch Gen Psychiatry 1987;44:461-469.Crossref 3. Morton NE, Chung CS: Genetic Epidemiology . Orlando, Fla, Academic Press Inc, 1978. 4. Sing C, Skolnick M: Genetic Analysis of Common Diseases: Applications to Predictive Factors in Coronary Diseases . New York, Alan R. Liss Inc, 1979. 5. Elandt-Johnson RC: Probability Models and Statistical Methods in Genetics . New York, John Wiley & Sons Inc, 1971. 6. Boyd JH, Weissman MM: Epidemiology of affective disorders: A reexamination and future directions . Arch Gen Psychiatry 1981;38:1039-1046.Crossref 7. Perris C: A study of bipolar (manic-depressives) and unipolar recurrent affective psychoses . Acta Psychiatr Scand 1966;42( (suppl 194) ):1-189.Crossref 8. Angst J: Zur ätiologie und Nosologie Endogener Depressiver Psychosen . Monogr Gesamtgeb Psychiatr 1966;112:1-118. 9. Gershon E, Mark A, Cohen N, Belizon N, Baron M, Knobe K: Transmitted factors in the morbid risk of affective disorders: A controlled study . J Psychiatr Res 1975;12:283-299.Crossref 10. Smeraldi E, Negri F, Melian AM: A genetic study of affective disorders . Acta Psychiatr Scand 1977;56:382-398.Crossref 11. Taylor MA, Abrams R, Hayman MA: The classification of affective disorders: A reassessment of the bipolar-unipolar dichotomy . J Affective Disord 1980;2:95-109.Crossref 12. Gershon ES, Hamovit S, Guroff JJ, Dibble E, Leckman JF, Sceery W, Targum SD, Nurnberger JI, Goldin LR, Bunney WE: A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands . Arch Gen Psychiatry 1982;39:1157-1167.Crossref 13. Winokur G, Tsuang MT, Crowe RR: The Iowa 500: Affective disorder in relatives of manic and depressed patients . Am J Psychiatry 1982;139:209-212. 14. Klerman GL, Lavori PW, Rice J: Birth cohort trends in rates of major depressive disorder among relatives of patients with affective disorder . Arch Gen Psychiatry 1985;42:689-693.Crossref 15. Spitzer RL, Endicott J, Robins E: Research Diagnostic Criteria (RDC)for a Selected Group of Functional Disorders . New York, New York State Psychiatric Institute, 1975. 16. Endicott J, Spitzer RL: A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia . Arch Gen Psychiatry 1978;35:837-844.Crossref 17. Strögren E: Zum Ersatz des Weinberg' schen 'abgekürzten Ver fahrens': Zugleich ein Beitrag zur Frage von der Erblichkeit des Erkrankungsalters bei der Schizophrenie . Zentralbl Ges Neurol Psychiatr 1935;153:764-797. 18. Kalbfleish JD, Prentice RL: The Statistical Analysis of Failure Time Data . New York, John Wiley & Sons Inc, 1980. 19. Preston DL, Clarkson DB: SURVREG: A program for the interactive analysis of survival regression analysis . Am Statistician 1983;37:174.Crossref 20. Morton NE, Rao DC, Lalouel J: Methods in Genetic Epidemiology . New York, S Karger AG, 1982. 21. Rice J, Reich T: Familial analysis of qualitative traits under multifactorial inheritance . Genet Epidemiol 1985;2:301-315.Crossref 22. Rice J, Cloninger CR, Reich T: General causal models for sex differences in the familial transmission of multifactorial traits: An application to human spatial visualizing ability . Soc Biol 1980;27:36-47. 23. Rice J, Nichols P, Gottesman II: Assessment of sex differences for qualitative multifactorial traits using path analysis . Psychiatry Res 1981;4:301-312.Crossref 24. Lalouel JM, Morton NE: Complex segregation analysis with pointers . Hum Hered 1981;31:312-321.Crossref 25. Lalouel JM, Rao DC, Morton NE, Elston RC: A unified model for complex segregation analysis . Am J Hum Genet 1983;35:816-826. 26. Elston RC, Yelverton KC: General models for segregation analysis . Am J Hum Genet 1975;27:31-45. 27. Robins LN, Helzer JE, Weissman MM, Orvaschel H, Gruenberg E, Burke JD, Regier D: Lifetime prevalence of specific psychiatric disorders in three sites . Arch Gen Psychiatry 1984;41:949-958.Crossref 28. Rice J, Cloninger CR, Reich T: Multifactorial inheritance with cultural transmission and assortative mating: I. Description and basic properties of the unitary models . Am J Hum Genet 1978;30:618-643. 29. Andreasen NC, Rice J, Endicott J, Reich T, Coryell W: The family history approach to diagnosis: How useful is it? Arch Gen Psychiatry 1986;43:421-429.Crossref 30. Lavori PW, Klerman GL, Keller MB, Reich T, Rice J, Endicott J: Ageperiod-cohort analysis of secular trends in onset of major depression: Findings in siblings of patients with major affective disorder . J Psychiatr Res , in press. 31. Weissman M, Myers J: Affective disorders in a United States urban community: The use of Research Diagnostic Criteria in an epidemiologic survey . Arch Gen Psychiatry 1978;35:1304-1311.Crossref 32. Hagnell 0, Lanke J, Rorsman B, Ojesjo L: Are we entering an age of melancholy? Depressive illnesses in a prospective epidemiological study over 25 years: Lundby study, Sweden . Psychol Med 1982;12:122-129. 33. Gershon ES, Hamovit JH, Guroff JJ, Nurnberger JI: Birth-cohort changes in manic and depressive disorders in relatives of bipolar and schizoaffective patients . Arch Gen Psychiatry 1987;44:314-319.Crossref 34. Weissman MM, Kidd KK, Prusoff BP: Variability in rates of affective disorders in relatives of depressed and normal probands . Arch Gen Psychiatry 1982;39:1397-1403.Crossref 35. Rice J, Reich T, Andreasen NC, Lavori PW, Endicott J, Clayton PJ, Keller MB, Hirschfeld RMA, Klerman GL: Sex related differences in depression: Familial evidence . J Affective Disord 1984;7:199-210.Crossref

Journal

Archives of General PsychiatryAmerican Medical Association

Published: May 1, 1987

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