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Psychiatric family history and schizophrenia risk in Denmark: which mental disorders are relevant?

Published online by Cambridge University Press:  17 July 2009

P. B. Mortensen ,
M. G. Pedersen  and
C. B. Pedersen
P. B. Mortensen*
Affiliation:
National Centre for Register-based Research, University of Aarhus, Aarhus, Denmark
M. G. Pedersen
Affiliation:
National Centre for Register-based Research, University of Aarhus, Aarhus, Denmark
C. B. Pedersen
Affiliation:
National Centre for Register-based Research, University of Aarhus, Aarhus, Denmark
*
*Address for correspondence: P. B. Mortensen, National Centre for Register-based Research, University of Aarhus, Taasingegade 1, 8000 Aarhus C, Denmark. (Email: pbm@ncrr.dk)
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Abstract

Background

A family history of schizophrenia is the strongest single indicator of individual schizophrenia risk. Bipolar affective disorder and schizo-affective disorders have been documented to occur more frequently in parents and siblings of schizophrenia patients, but the familial occurrence of the broader range of mental illnesses and their role as confounders have not been studied in large population-based samples.

Method

All people born in Denmark between 1955 and 1991 (1.74 million) were followed for the development of schizophrenia (9324 cases) during 28 million person-years at risk. Information of schizophrenia in cohort members and psychiatric history in parents and siblings was established through linkage with the Danish Psychiatric Central Register. Data were analysed using log-linear Poisson regression.

Results

Schizophrenia was, as expected, strongly associated with schizophrenia and related disorders among first-degree relatives. However, almost any other psychiatric disorder among first-degree relatives increased the individual's risk of schizophrenia. The population attributable risk associated with psychiatric family history in general was 27.1% whereas family histories including schizophrenia only accounted for 6.0%. The general psychiatric family history was a confounder of the association between schizophrenia and urbanization of place of birth.

Conclusions

Clinically diagnosed schizophrenia is associated with a much broader range of mental disorders in first-degree relatives than previously reported. This may suggest risk haplotypes shared across many disorders and/or shared environmental factors clustering in families. Failure to take the broad range of psychiatric family history into account may bias results of all risk-factor studies of schizophrenia.

Keywords

Family historypopulation-basedrisk factorschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 40 , Issue 2 , February 2010 , pp. 201 - 210
Copyright
Copyright © Cambridge University Press 2009

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References

Andersen, PK, Borgan, Ø, Gill, RD, Keiding, N (1997). Statistical Models Based on Counting Processes. Springer: New York.Google Scholar
Baron, M, Gruen, R, Rainer, JD, Kane, J, Asnis, L, Lord, S (1985). A family study of schizophrenic and normal control probands – implications for the spectrum concept of schizophrenia. American Journal of Psychiatry 142, 447–455.Google ScholarPubMed
Breslow, NE (1996). Generalized linear models: checking assumptions and strengthening conclusions. Statistica Applicata 8, 23–41.Google Scholar
Breslow, NE, Day, NE (1987). Statistical Methods in Cancer Research Volume II – The Design and Analysis of Cohort Studies. IARC Scientific Publications: Lyon.Google ScholarPubMed
Bruzzi, P, Green, SB, Byar, DP, Brinton, LA, Schairer, C (1985). Estimating the population attributable risk for multiple risk factors using case-control data. American Journal of Epidemiology 122, 904–914.CrossRefGoogle ScholarPubMed
Cardno, AG, Rijsdijk, FV, Sham, PC, Murray, RM, McGuffin, P (2002). A twin study of genetic relationships between psychotic symptoms. American Journal of Psychiatry 159, 539–545.CrossRefGoogle ScholarPubMed
Chubb, JE, Bradshaw, NJ, Soares, DC, Porteous, DJ, Millar, JK (2008). The DISC locus in psychiatric illness. Molecular Psychiatry 13, 36–64.CrossRefGoogle ScholarPubMed
Clayton, D, Hills, M (1993). Statistical Models in Epidemiology. Oxford University Press: Oxford, New York, Tokyo.Google Scholar
Craddock, N, O'Donovan, MC, Owen, MJ (2006). Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology. Schizophrenia Bulletin 32, 9–16.CrossRefGoogle ScholarPubMed
Gershon, ES, DeLisi, LE, Hamovit, J, Nurnberger, JI, Maxwell, ME, Schreiber, J, Dauphinais, D, Dingman, CW, Guroff, JJ (1988). A controlled family study of chronic psychoses – schizophrenia and schizoaffective disorder. Archives of General Psychiatry 45, 328–336.CrossRefGoogle ScholarPubMed
Gottesman, II (1991). Schizophrenia Genesis. The Origins of Madness. W. H. Freeman and Company: New York.Google Scholar
Henriksson, MM, Aro, HM, Marttunen, MJ, Heikkinen, ME, Isometsa, ET, Kuoppasalmi, KI, Lonnqvist, JK (1993). Mental disorders and comorbidity in suicide. American Journal of Psychiatry 150, 935–940.Google ScholarPubMed
Heun, R, Kockler, M, Ptok, U (2002). Psychiatric disorders in relatives of subjects with Alzheimer's disease. No evidence for common genetic risk factors. European Archives of Psychiatry and Clinical Neuroscience 252, 93–97.CrossRefGoogle ScholarPubMed
Juel, K, Helweg-Larsen, K (1999). The Danish registers of causes of death. Danish Medical Bulletin 46, 354–357.Google ScholarPubMed
Kendler, KS, Gardner, CO (1997). The risk for psychiatric disorders in relatives of schizophrenic and control probands: a comparison of three independent studies. Psychological Medicine 27, 411–419.CrossRefGoogle ScholarPubMed
Kendler, KS, McGuire, M, Gruenberg, AM, Ohare, A, Spellman, M, Walsh, D (1993 a). The Roscommon Family Study. 1. Methods, diagnosis of probands, and risk of schizophrenia in relatives. Archives of General Psychiatry 50, 527–540.CrossRefGoogle ScholarPubMed
Kendler, KS, McGuire, M, Gruenberg, AM, Ohare, A, Spellman, M, Walsh, D (1993 b). The Roscommon Family Study. 3. Schizophrenia-related personality-disorders in relatives. Archives of General Psychiatry 50, 781–788.CrossRefGoogle Scholar
Kendler, KS, McGuire, M, Gruenberg, AM, Spellman, M, Ohare, A, Walsh, D (1993 c). The Roscommon Family Study. 2. The risk of nonschizophrenic nonaffective psychoses in relatives. Archives of General Psychiatry 50, 645–652.CrossRefGoogle Scholar
Kety, SS, Rosenthal, D, Wender, PH, Schulsinger, F (1968). The types and prevalence of mental illness in the biological and adoptive families of adopted schizophrenics. In The Transmission of Schizophrenia (ed. Rosenthal, D. and Kety, S. S.), pp. 345–362. Pergamon Press: Oxford, London, Edinburgh, New York.Google Scholar
Laursen, TM, Labouriau, R, Licht, RW, Bertelsen, A, Munk-Olsen, T, Mortensen, PB (2005). Family history of psychiatric illness as risk factor for schizoaffective disorder. Archives of General Psychiatry 62, 841–848.CrossRefGoogle ScholarPubMed
Lichtenstein, P, Yip, BH, Bjork, C, Pawitan, Y, Cannon, TD, Sullivan, PF, Hultman, CM (2009). Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373, 234–239.CrossRefGoogle ScholarPubMed
Maier, W, Hofgen, B, Zobel, A, Rietschel, M (2005). Genetic models of schizophrenia and bipolar disorder: overlapping inheritance or discrete genotypes? European Archives of Psychiatry and Clinical Neuroscience 255, 159–166.CrossRefGoogle ScholarPubMed
McDonald, C, Bullmore, ET, Sham, PC, Chitnis, X, Wickham, H, Bramon, E, Murray, RM (2004). Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes. Archives of General Psychiatry 61, 974–984.CrossRefGoogle ScholarPubMed
Morrison, AC, Bare, LA, Chambless, LE, Ellis, SG, Malloy, M, Kane, JP, Pankow, JS, Devlin, JJ, Willerson, JT, Boerwinkle, E (2007). Prediction of coronary heart disease risk using a genetic risk score: the Atherosclerosis Risk in Communities Study. American Journal of Epidemiology 166, 28–35.CrossRefGoogle ScholarPubMed
Mortensen, PB, Pedersen, CB, Westergaard, T, Wohlfahrt, J, Ewald, H, Mors, O, Andersen, PK, Melbye, M (1999). Effects of family history and place and season of birth on the risk of schizophrenia. New England Journal of Medicine 340, 603–608.CrossRefGoogle ScholarPubMed
Munk-Jørgensen, P, Mortensen, PB (1997). The Danish Psychiatric Central Register. Danish Medical Bulletin 44, 82–84.Google ScholarPubMed
Onstad, S, Skre, I, Edvardsen, J, Torgersen, S, Kringlen, E (1991). Mental disorders in first-degree relatives of schizophrenics. Acta Psychiatrica Scandinavica 83, 463–467.CrossRefGoogle ScholarPubMed
Owen, MJ, Craddock, N, Jablensky, A (2007). The genetic deconstruction of psychosis. Schizophrenia Bulletin 33, 905–911.CrossRefGoogle ScholarPubMed
Parnas, J, Cannon, TD, Jacobsen, B, Schulsinger, H, Schulsinger, F, Mednick, SA (1993). Lifetime DSM-III-R diagnostic outcomes in the offspring of schizophrenic mothers. Results from the Copenhagen High-Risk Study. Archives of General Psychiatry 50, 707–714.CrossRefGoogle ScholarPubMed
Pedersen, CB (2006). No evidence of time trends in the urban–rural differences in schizophrenia risk among five million people born in Denmark from 1910 to 1986. Psychological Medicine 36, 211–219.CrossRefGoogle ScholarPubMed
Pedersen, CB, Gøtzsche, H, Møller, JO, Mortensen, PB (2006). The Danish Civil Registration System. Danish Medical Bulletin 53, 441–449.Google ScholarPubMed
Pedersen, CB, Mortensen, PB (2001). Family history, place and season of birth as risk factors for schizophrenia in Denmark: a replication and reanalysis. British Journal of Psychiatry 179, 46–52.CrossRefGoogle Scholar
SAS Institute Inc. (2004). The GENMOD procedure. In SAS/STAT 9.1 User's Guide, pp. 1609–1730. SAS Institute Inc.: Cary, NC.Google Scholar
Statistics Denmark (1997). The Population in Danish Municipalities. Statistics Denmark: Copenhagen.Google Scholar
Stefansson, H, Rujescu, D, Cichon, S, Pietilainen, OPH, Ingason, A, Steinberg, S, Fossdal, R, Sigurdsson, E, Sigmundsson, T, Buizer-Voskamp, JE, Hansen, T, Jakobsen, KD, Muglia, P, Francks, C, Matthews, PM, Gylfason, A, Halldorsson, BV, Gudbjartsson, D, Thorgeirsson, TE, Sigurdsson, A, Jonasdottir, A, Jonasdottir, A, Bjornsson, A, Mattiasdottir, S, Blondal, T, Haraldsson, M, Magnusdottir, BB, Giegling, I, Moller, HJ, Hartmann, A, Shianna, KV, Ge, DL, Need, AC, Crombie, C, Fraser, G, Walker, N, Lonnqvist, J, Suvisaari, J, Tuulio-Henriksson, A, Paunio, T, Toulopoulou, T, Bramon, E, Di Forti, M, Murray, R, Ruggeri, M, Vassos, E, Tosato, S, Walshe, M, Li, T, Vasilescu, C, Muhleisen, TW, Wang, AG, Ullum, H, Djurovic, S, Melle, I, Olesen, J, Kiemeney, LA, Franke, B, Sabatti, C, Freimer, NB, Gulcher, JR, Thorsteinsdottir, U, Kong, A, Andreassen, OA, Ophoff, RA, Georgi, A, Rietschel, M, Werge, T, Petursson, H, Goldstein, DB, Nothen, MM, Peltonen, L, Collier, DA, St Clair, D, Stefansson, K (2008). Large recurrent microdeletions associated with schizophrenia. Nature 455, 232–236.CrossRefGoogle ScholarPubMed
Sullivan, PF, Kendler, KS, Neale, MC (2003). Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Archives of General Psychiatry 60, 1187–1192.CrossRefGoogle ScholarPubMed
Van Os, J, Rutten, BP, Poulton, R (2008). Gene–environment interactions in schizophrenia: review of epidemiological findings and future directions. Schizophrenia Bulletin 34, 1066–1082.CrossRefGoogle ScholarPubMed
WHO (1967). Manual of the International Classification of Diseases (ICD-8). World Health Organization: Geneva.Google Scholar
WHO (1992). The ICD-10 Classification of Mental and Behavioural Disorders. Clinical Descriptions and Diagnostic Guidelines. World Health Organization: Geneva.Google Scholar
Wray, NR, Goddard, ME, Visscher, PM (2008). Prediction of individual genetic risk of complex disease. Current Opinion in Genetics and Development 18, 257–263.CrossRefGoogle ScholarPubMed