Skip to main content

Advertisement

SpringerLink
Log in

Heritability of schizophrenia and major affective disorder as a function of age, in the presence of strong cohort effects

  • ORIGINAL PAPER
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

It remains unclear whether age at onset for major psychiatric disorders is a useful marker of etiologic and genetic heterogeneity. The authors examined how heritability of schizophrenia and major affective disorders varied with age at onset. The sample was drawn from a large archival data set collected by Lionel Penrose, comprising 3,109 families with two or more members first hospitalized in Ontario between 1874 and 1944. The authors studied 1,295 sibships with schizophrenia (n = 487), major affective disorder (n = 378), both (n = 234) or neither (n = 196) of these disorders. Proportional hazards models were used to estimate how the hazard of hospitalization for each disorder (schizophrenia or major affective disorder) varied with proband age at onset, adjusted for changes in age at onset distribution between 1874 and 1944. A sibling's risk of hospitalization for the same illness significantly increased for each 10–year decrease in age at onset of the proband both for schizophrenia (hazard ratio = 1.21, 95 % confidence interval: 1.06, 1.39), and for affective disorder (hazard ratio = 1.29,95 % CI: 1.14, 1.45). Gender of proband was unrelated to sibling risk of the same illness, and tests of interaction effects between proband age at onset and gender on sibling risk were nonsignificant.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Albus M, Scherer J, Hueber S, Lechleuthner T, Kraus G, Zausinger S, Burkes S (1994) The impact of familial loading on gender differences in age at onset of schizophrenia. Acta Psychiatr Scand 89:132–134

    PubMed  CAS  Google Scholar 

  2. Alda M, Ahrens B, Lit W, Dvorakova M, Labelle A, Zvolsky P, Jones B (1996) Age of onset in familial and sporadic schizophrenia. Acta Psychiatr Scand 93:447–450

    PubMed  CAS  Google Scholar 

  3. Bassett AS, Chow EWC, O'Neill S, Brzustowicz LM (2001) Genetic insights into the neurodevelopmental hypothesis of schizophrenia. Schizophr Bull 27:417–430

    PubMed  CAS  Google Scholar 

  4. Bassett AS, Husted J (1997) Anticipation or ascertainment bias in schizophrenia? Penrose’s familial mental illness sample. Am J Hum Genet 60:630–637

    PubMed  CAS  Google Scholar 

  5. Bellivier F, Golmard J–L, Rietschel M, Schulze T, Malafosse A, Preisig M, McKeon P, Mynett–Johnson L, Henry C, Leboyer M (2003) Age at onset in Bipolar I affective disorder: Further evidence for three subgroups. Am J Psychiatry 160:999–1001

    Article  PubMed  Google Scholar 

  6. Berrettini WH (2000) Are schizophrenic and bipolar disorders related? A review of family and molecular studies. Biol Psychiatry 48:531–538

    Article  PubMed  CAS  Google Scholar 

  7. Cox DR (1972) Regression models and life tables (with discussion). J Royal Stat Soci Brit 34

  8. Crow TJ (1991) A note on “Survey of cases of familial mental illness” by LS Penrose. Eur Arch Psychiatry Clin Neurosci 240:314–315

    Article  Google Scholar 

  9. Crow TJ (1988) Sex chromosomes and psychosis: The case for a pseudoautosomal locus. Br J Psychiatry 153:675–683

    PubMed  CAS  Google Scholar 

  10. DeLisi LE (1992) The significance of age of onset for schizophrenia. Schizophr Bull 18:209–215

    PubMed  CAS  Google Scholar 

  11. Forrester A, Owens DGC, Johnstone EC (2001) Diagnostic stability in subjects with multiple admissions for psychotic illness. Psychol Med 31:151–158

    Article  PubMed  CAS  Google Scholar 

  12. Gentleman R, Ihaka R (2003) A language and environment for statistical computing. In: R Foundation for Statistical Computing, Vienna, Austria

  13. George–Hyslop PH, Haines JL, Farrer LA, Polinsky R, Van Broeckhoven C, Goate A, MacLachlan DRC (1990) Genetic linkage studies suggest that Alzheimer’s disease is not a single homogeneous disorder. Nature 347:194–197

    Article  Google Scholar 

  14. Gorwood P, Leboyer M, Jay M, Payan C, Feingold J (1995) Gender impact and age at onset in schizophrenia: Impact of family history. Am J Psychiatry 152:208–212

    PubMed  CAS  Google Scholar 

  15. Grigoroiu–Serbanescu M, Martinez M, Nöthen M, Grinberg M, Sima D, Propping P, Marinescu E, Hrestic M (2001) Differential transmission patterns in Bipolar I disorder with onset before and after age 25. Am J Med Genet (Neuropsychiatric Genetics) 105:765–773

    Article  PubMed  CAS  Google Scholar 

  16. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, King M–C (1990) Linkage of early–onset familial breast cancer to chromosome 17q21. Science 250:1684–1689

    PubMed  CAS  Google Scholar 

  17. Johnson L, Andersson–Lundman G, Åberg–Wistedt A, Mathé A (2000) Age of onset in affective disorder: its correlation with hereditary and psychosocial factors. J Affect Disord 59:139–148

    Article  PubMed  CAS  Google Scholar 

  18. Kendler KS, Diehl SR (1993) The genetics of schizophrenia: A current, genetic–epidemiologic perspective. Schizophr Bull 19:261–285

    PubMed  CAS  Google Scholar 

  19. Kendler KS, Karkowski–Shuman L, Walsh D (1996) Age at onset in schizophrenia and risk of illness in relatives. Results from the Roscommon Family Study. Br J Psychiatry 169:213–218

    PubMed  CAS  Google Scholar 

  20. Kendler KS, MacLean CJ (1990) Estimating familial effects on age at onset and liability to schizophrenia: I. Results of a large sample family study. Genet Epidemiol 7:409–417

    Article  PubMed  CAS  Google Scholar 

  21. Kendler KS, Tsuang MT, Hays P (1987) Age at onset in schizophrenia: A familial perspective. Arch Gen Psychiatry 44:881–890

    PubMed  CAS  Google Scholar 

  22. Link B, Dohrenwend B (1980) Formulation of hypothesis about the ratio of untreated to treated cases in the true prevalence studies of functional psychiatric disorders in adults in the United States. In: Dohrenwend BP, Dohrenwend BS, Schwartz Gould M, Link B, Neugebauer R, Wunsch–Hitzig R (eds) Mental Illness in the United States: Epidemiologic Estimates. Praeger, New York

  23. Lipsitz SR, Dear KB, Zhao L (1994) Jackknife estimators of variance for parameter estimates from estimating equations with applications to clustered survival data. Biometrics 50:842–846

    PubMed  CAS  Google Scholar 

  24. Little R, Rubin D (1987) Statistical analysis with missing data. J. Wiley and Sons, New York

  25. Lunn M, McNeil D (1995) Applying Cox regression to competing risks. Biometrics 51:524–532

    PubMed  CAS  Google Scholar 

  26. Maier W, Lichtermann D, Minges J, Heun R, Hallmayer J (1993) The impact of gender and age at onset on the familial aggregation of schizophrenia. Eur Arch Psychiatry Clin Neurosci 242:279–285

    Article  PubMed  CAS  Google Scholar 

  27. OMahoney E, Corvin A, O'Connell R, Comerford C, Larsen B, Jones R, McCandless F, Kirove G, Cardno AG, Craddock N, Gill M (2002) Sibling pairs with affective disorders: Resemblance of demographic and clinical features. Psychol Med 32:55–61

    Google Scholar 

  28. Penrose LS (1991) Survey of cases of familial mental illness. Eur Arch Psychiatry Clin Neurosci 240:315–324

    Article  PubMed  CAS  Google Scholar 

  29. Pulver AE, Liang KY (1991) Estimating effects of proband characteristics on familial risk: II. The association between age at onset and familial risk in the Maryland schizophrenia sample. Genet Epidemiol 8:339–350

    Article  PubMed  CAS  Google Scholar 

  30. Risch N (1990) Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet 46:222–228

    PubMed  CAS  Google Scholar 

  31. Schurhoff F, Bellivier F, Jouvent R, Mouren–Simeoni MC, Bouvard M, Allilaire JF, Leboyer M (2000) Early and late onset bipolar disorders: two different forms of manic–depressive illness? J Affect Disord 58:215–221

    Article  PubMed  CAS  Google Scholar 

  32. Sham PC, Jones P, Russell A, Gilvarry K, Bebbington P, Lewis S, Toone B, Murray R (1994) Age at onset, sex, and familial psychiatric morbidity in schizophrenia: Camberwell Collaborative Psychosis Study. Br J Psychiatry 165:466–473

    PubMed  CAS  Google Scholar 

  33. Sham PC, MacLean CJ, Kendler KS (1994) A typological model of schizophrenia based on age at onset, sex and familial morbidity. Acta Psychiatr Scand 89:135–141

    PubMed  CAS  Google Scholar 

  34. Somanath CP, Jain S, Reddy YC (2002) A family study of early–onset bipolar I disorder. J Affect Disord 70:91–94

    Article  PubMed  CAS  Google Scholar 

  35. Suvisaari JM, Taukka J, Tanskanen A, Lonnqvist JK (1998) Age at onset and outcome in schizophrenia are related to the degree of familial loading. Br J Psychiatry 173:494–500

    Article  PubMed  CAS  Google Scholar 

  36. Therneau TM (1996) Extending the Cox model. In:Mayo Clinic, Rochester, Minnesota

  37. Tsuang MT (1967) A study of pairs of sibs both hospitalized for mental disorder. Br J Psychiatry 113:283–300

    Article  PubMed  CAS  Google Scholar 

  38. Vogler GP, Gottesman II, McGue MK, Rao DC (1990) Mixedmodel segregation analysis of schizophrenia in the lindelius Swedish pedigrees. Behav Genet 20:461–472

    Article  PubMed  CAS  Google Scholar 

  39. Waddington J, Youssef H (1996) Familial–genetic and reproductive epidemiology of schizophrenia in rural Ireland: age at onset, familial morbidity risk and parental fertility. Acta Psychiatr 93:62–68

    CAS  Google Scholar 

  40. Weissman MM, Gershon ES, Kidd KK, Prusoff BA, Leckman JF, Dibble E, Hamovit J, Thompson WD, Pauls DL, Guroff JJ (1984) Psychiatric disorders in the relatives of probands with affective disorder. Arch Gen Psychiatry 41:13–21

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, Ontario, Canada

    C. M. T. Greenwood PhD

  2. Department of Public Health Sciences, University of Toronto, Ontario, Canada

    C. M. T. Greenwood PhD

  3. Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    A. S. Bassett MD, FRCPC

  4. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    A. S. Bassett MD, FRCPC

  5. Department of Health Studies and Gerontology, University ofWaterloo, Waterloo, Ontario N2L 3G1, Canada

    J. Husted PhD

Authors
  1. J. Husted PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. M. T. Greenwood PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. S. Bassett MD, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Husted PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Husted, J., Greenwood, C.M.T. & Bassett, A.S. Heritability of schizophrenia and major affective disorder as a function of age, in the presence of strong cohort effects. Eur Arch Psychiatry Clin Neurosci 256, 222–229 (2006). https://doi.org/10.1007/s00406-005-0629-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-005-0629-z

Key words

Search

Navigation