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Lifetime reproductive output over two generations in patients with psychosis and their unaffected siblings: the Uppsala 1915–1929 Birth Cohort Multigenerational Study

Published online by Cambridge University Press:  06 March 2009

J. H. MacCabe*
Affiliation:
Department of Psychiatry, Institute of Psychiatry, King's College London, UK
I. Koupil
Affiliation:
Centre for Health Equity Studies (CHESS), Stockholms Universitet/Karolinska Institutet, Stockholm, Sweden
D. A. Leon
Affiliation:
London School of Hygiene and Tropical Medicine (LSHTM), London, UK
*
*Address for correspondence: Dr J. H. MacCabe, B.Sc., MBBS, MRCPsych, M.Sc., Ph.D., Clinical Lecturer in Psychiatry, Department of Psychiatry, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. (Email: [email protected])

Abstract

Background

Schizophrenic patients have fewer offspring than the general population but it is unclear whether (i) this persists for more than one generation, (ii) the reduced fertility is compensated by increased fertility in unaffected relatives, (iii) sociodemographic factors confound or interact with the association, and (iv) patients with affective psychosis have a similar fertility disadvantage. This study measured biological fitness over two generations in patients with schizophrenia or affective psychosis, and their unaffected siblings.

Method

We conducted a historical cohort study using a Swedish birth cohort of 12 168 individuals born 1915–1929 and followed up until 2002. We compared biological fitness over two generations in patients with schizophrenia (n=58) or affective psychosis (n=153), and their unaffected siblings, with the population, adjusting for a range of sociodemographic variables from throughout the lifespan.

Results

Patients with schizophrenia had fewer children [fertility ratio (FR) 0.42, 95% confidence interval (CI) 0.29–0.61] and grandchildren (FR 0.51, 95% CI 0.33–0.80) than the population. Some of this reduction was related to lower marriage rates in schizophrenic patients. The unaffected siblings of schizophrenic patients showed no evidence of any compensatory increase in fitness, but there was a trend towards enhanced fertility among the offspring of schizophrenia patients. Patients with affective psychosis and their relatives did not differ from the general population on any fertility measure.

Conclusions

Schizophrenia, but not affective psychosis, is associated with reduced biological fertility; this disadvantage is partly explained by marital status and persists into the second generation.

Type
Original Articles
Copyright
Copyright © 2009 Cambridge University Press

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References

Aizenberg, D, Zemishlany, Z, Dorfman-Etrog, P, Weizman, A (1995). Sexual dysfunction in male schizophrenic patients. Journal of Clinical Psychiatry 56, 137141.Google ScholarPubMed
Armstrong, C (1997). Thousands of women sterilised in Sweden without consent. British Medical Journal 315, 563.CrossRefGoogle ScholarPubMed
Battaglia, M, Bellodi, L (1996). Familial risks and reproductive fitness in schizophrenia. Schizophrenia Bulletin 22, 191195.CrossRefGoogle ScholarPubMed
Bhatia, T, Franzos, MA, Wood, JA, Nimgaonkar, VL, Deshpande, SN (2004). Gender and procreation among patients with schizophrenia. Schizophrenia Research 68, 387394.CrossRefGoogle ScholarPubMed
Buck, GM, Sever, LE, Batt, RE, Mendola, P (1997). Life-style factors and female infertility. Epidemiology 8, 435441.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, 539545.CrossRefGoogle ScholarPubMed
Dalman, C, Broms, J, Cullberg, J, Allebeck, P (2002). Young cases of schizophrenia identified in a national inpatient register – are the diagnoses valid? Social Psychiatry and Psychiatric Epidemiology 37, 527531.CrossRefGoogle Scholar
Fananas, L, Bertranpetit, J (1995). Reproductive rates in families of schizophrenic patients in a case-control study. Acta Psychiatrica Scandinavica 91, 202204.CrossRefGoogle ScholarPubMed
Fortier, P, Mottard, JP, Trudel, G, Even, S (2003). Study of sexuality-related characteristics in young adults with schizophrenia treated with novel neuroleptics and in a comparison group of young adults. Schizophrenia Bulletin 29, 559572.CrossRefGoogle Scholar
Gardner, W, Mulvey, EP, Shaw, EC (1995). Regression analyses of counts and rates: Poisson, overdispersed Poisson, and negative binomial models. Psychological Bulletin 118, 392404.CrossRefGoogle ScholarPubMed
Garpenby, P (1993). From ideology to reality: mental health care in Sweden. European Journal of Public Health 3, 296298.CrossRefGoogle Scholar
Hansson, L (1989). Utilization of psychiatric inpatient care. A study of changes related to the introduction of a sectorized care organization. Acta Psychiatrica Scandinavica 79, 571578.CrossRefGoogle Scholar
Harrison, G, Hopper, K, Craig, T, Laska, E, Siegel, C, Wanderling, J, Dube, KC, Ganev, K, Giel, R, an der Heiden, W, Holmberg, SK, Janca, A, Lee, PW, Leon, CA, Malhotra, S, Marsella, AJ, Nakane, Y, Sartorius, N, Shen, Y, Skoda, C, Thara, R, Tsirkin, SJ, Varma, VK, Walsh, D, Wiersma, D (2001). Recovery from psychotic illness: a 15- and 25-year international follow-up study. British Journal of Psychiatry 178, 506517.CrossRefGoogle ScholarPubMed
Haukka, J, Suvisaari, J, Lonnqvist, J (2003). Fertility of patients with schizophrenia, their siblings, and the general population: a cohort study from 1950 to 1959 in Finland. American Journal of Psychiatry 160, 460463.CrossRefGoogle ScholarPubMed
Howard, LM, Kumar, C, Leese, M, Thornicroft, G (2002). The general fertility rate in women with psychotic disorders. American Journal of Psychiatry 159, 991997.CrossRefGoogle ScholarPubMed
Hutchinson, G, Bhugra, D, Mallett, R, Burnett, R, Corridan, B, Leff, J (1999). Fertility and marital rates in first-onset schizophrenia. Social Psychiatry and Psychiatric Epidemiology 34, 617621.CrossRefGoogle ScholarPubMed
Huxley, J, Mayr, E, Osmond, H, Hoffer, A (1964). Schizophrenia as a genetic morphism. Nature 204, 220221.CrossRefGoogle ScholarPubMed
International Schizophrenia Consortium (2008). Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455, 237241.CrossRefGoogle Scholar
Jablensky, AV, Kalaydjieva, LV (2003). Genetic epidemiology of schizophrenia: phenotypes, risk factors, and reproductive behavior. American Journal of Psychiatry 160, 425429.CrossRefGoogle ScholarPubMed
Keller, MC, Miller, G (2006). Resolving the paradox of common, harmful, heritable mental disorders: which evolutionary genetic models work best? Behavioural and Brain Sciences 29, 385404; discussion 405452.CrossRefGoogle ScholarPubMed
Koupil, I (2007). The Uppsala studies on developmental origins of health and disease. Journal of Internal Medicine 261, 426436.CrossRefGoogle ScholarPubMed
Leon, DA, Lithell, HO, Vagero, D, Koupilova, I, Mohsen, R, Berglund, L, Lithell, UB, McKeigue, PM (1998). Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915–29. British Medical Journal 317, 241245.CrossRefGoogle Scholar
Leonard, S, Adler, LE, Benhammou, K, Berger, R, Breese, CR, Drebing, C, Gault, J, Lee, MJ, Logel, J, Olincy, A, Ross, RG, Stevens, K, Sullivan, B, Vianzon, R, Virnich, DE, Waldo, M, Walton, K, Freedman, R (2001). Smoking and mental illness. Pharmacology, Biochemistry, and Behavior 70, 561570.CrossRefGoogle ScholarPubMed
McGrath, JJ, Hearle, J, Jenner, L, Plant, K, Drummond, A, Barkla, JM (1999). The fertility and fecundity of patients with psychoses. Acta Psychiatrica Scandinavica 99, 441446.CrossRefGoogle ScholarPubMed
Meaney, AM, O'Keane, V (2002). Prolactin and schizophrenia: clinical consequences of hyperprolactinaemia. Life Sciences 71, 979992.CrossRefGoogle ScholarPubMed
Muthusami, KR, Chinnaswamy, P (2005). Effect of chronic alcoholism on male fertility hormones and semen quality. Fertility and Sterility 84, 919924.CrossRefGoogle ScholarPubMed
Nettle, D (2001). Strong Imagination: Madness, Creativity and Human Nature. Oxford University Press: Oxford.CrossRefGoogle Scholar
Nimgaonkar, VL, Ward, SE, Agarde, H, Weston, N, Ganguli, R (1997). Fertility in schizophrenia: results from a contemporary US cohort. Acta Psychiatrica Scandinavica 95, 364369.CrossRefGoogle ScholarPubMed
Priebe, S, Badesconyi, A, Fioritti, A, Hansson, L, Kilian, R, Torres-Gonzales, F, Turner, T, Wiersma, D (2005). Reinstitutionalisation in mental health care: comparison of data on service provision from six European countries. British Medical Journal 330, 123126.CrossRefGoogle ScholarPubMed
Runcis, M (1998). Sterilization in the Swedish Welfare State [in Swedish]. Ordfront: Stockholm.Google Scholar
Sipos, A, Rasmussen, F, Harrison, G, Tynelius, P, Lewis, G, Leon, DA, Gunnell, D (2004). Paternal age and schizophrenia: a population based cohort study. British Medical Journal 329, 1070.CrossRefGoogle ScholarPubMed
Sober, E (2001). The two faces of fitness. In Thinking About Evolution: Historical, Philosophical, and Political Perspectives (ed. Singh, R., Paul, D., Krimbas, C. and Beatty, J.), pp. 309321. Cambridge University Press: Cambridge.Google Scholar
Srinivasan, TN, Padmavati, R (1997). Fertility and schizophrenia: evidence for increased fertility in the relatives of schizophrenic patients. Acta Psychiatrica Scandinavica 96, 260264.CrossRefGoogle ScholarPubMed
Stefansson, H, Rujescu, D, Cichon, S, Pietilainen, OP, 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, D, 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, Kahn, RS, Linszen, DH, van Os, J, Wiersma, D, Bruggeman, R, Cahn, W, de Haan, L, Krabbendam, L, Myin-Germeys, I (2008). Large recurrent microdeletions associated with schizophrenia. Nature 455, 232236.CrossRefGoogle ScholarPubMed
Svensson, AC, Lichtenstein, P, Sandin, S, Hultman, CM (2007). Fertility of first-degree relatives of patients with schizophrenia: a three generation perspective. Schizophrenia Research 91, 238245.CrossRefGoogle ScholarPubMed
Tannsjo, T (1998). Compulsory sterilisation in Sweden. Bioethics 12, 236249.CrossRefGoogle ScholarPubMed
Van Mastrigt, S, Addington, J, Addington, D (2004). Substance misuse at presentation to an early psychosis program. Social Psychiatry and Psychiatric Epidemiology 39, 6972.CrossRefGoogle Scholar
Walsh, B (2003). Evolutionary quantitative genetics. In Handbook of Statistical Genetics (ed. Balding, D.J., Bishop, M. and Cannings, C.), pp. 389438. John Wiley and Sons, Ltd: Chichester.Google Scholar
Walsh, T, McClellan, JM, McCarthy, SE, Addington, AM, Pierce, SB, Cooper, GM, Nord, AS, Kusenda, M, Malhotra, D, Bhandari, A, Stray, SM, Rippey, CF, Roccanova, P, Makarov, V, Lakshmi, B, Findling, RL, Sikich, L, Stromberg, T, Merriman, B, Gogtay, N, Butler, P, Eckstrand, K, Noory, L, Gochman, P, Long, R, Chen, Z, Davis, S, Baker, C, Eichler, EE, Meltzer, PS, Nelson, SF, Singleton, AB, Lee, MK, Rapoport, JL, King, MC, Sebat, J (2008). Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320, 539543.CrossRefGoogle ScholarPubMed
WHO (1992). International Statistical Classification of Diseases and Related Health Problems. World Health Organization: Geneva.Google Scholar
Xu, B, Roos, JL, Levy, S, van Rensburg, EJ, Gogos, JA, Karayiorgou, M (2008). Strong association of de novo copy number mutations with sporadic schizophrenia. Nature Genetics 40, 880885.CrossRefGoogle ScholarPubMed