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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

  • J. H. MacCabe (a1), I. Koupil (a2) and D. A. Leon (a3)

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.


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.


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.


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.

Corresponding author
*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:
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Aizenberg D, Zemishlany Z, Dorfman-Etrog P, Weizman A (1995). Sexual dysfunction in male schizophrenic patients. Journal of Clinical Psychiatry 56, 137141.
Armstrong C (1997). Thousands of women sterilised in Sweden without consent. British Medical Journal 315, 563.
Battaglia M, Bellodi L (1996). Familial risks and reproductive fitness in schizophrenia. Schizophrenia Bulletin 22, 191195.
Bhatia T, Franzos MA, Wood JA, Nimgaonkar VL, Deshpande SN (2004). Gender and procreation among patients with schizophrenia. Schizophrenia Research 68, 387394.
Buck GM, Sever LE, Batt RE, Mendola P (1997). Life-style factors and female infertility. Epidemiology 8, 435441.
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.
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.
Fananas L, Bertranpetit J (1995). Reproductive rates in families of schizophrenic patients in a case-control study. Acta Psychiatrica Scandinavica 91, 202204.
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.
Gardner W, Mulvey EP, Shaw EC (1995). Regression analyses of counts and rates: Poisson, overdispersed Poisson, and negative binomial models. Psychological Bulletin 118, 392404.
Garpenby P (1993). From ideology to reality: mental health care in Sweden. European Journal of Public Health 3, 296298.
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.
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.
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.
Howard LM, Kumar C, Leese M, Thornicroft G (2002). The general fertility rate in women with psychotic disorders. American Journal of Psychiatry 159, 991997.
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.
Huxley J, Mayr E, Osmond H, Hoffer A (1964). Schizophrenia as a genetic morphism. Nature 204, 220221.
International Schizophrenia Consortium (2008). Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455, 237241.
Jablensky AV, Kalaydjieva LV (2003). Genetic epidemiology of schizophrenia: phenotypes, risk factors, and reproductive behavior. American Journal of Psychiatry 160, 425429.
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.
Koupil I (2007). The Uppsala studies on developmental origins of health and disease. Journal of Internal Medicine 261, 426436.
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.
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.
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.
Meaney AM, O'Keane V (2002). Prolactin and schizophrenia: clinical consequences of hyperprolactinaemia. Life Sciences 71, 979992.
Muthusami KR, Chinnaswamy P (2005). Effect of chronic alcoholism on male fertility hormones and semen quality. Fertility and Sterility 84, 919924.
Nettle D (2001). Strong Imagination: Madness, Creativity and Human Nature. Oxford University Press: Oxford.
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.
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.
Runcis M (1998). Sterilization in the Swedish Welfare State [in Swedish]. Ordfront: Stockholm.
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.
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.
Srinivasan TN, Padmavati R (1997). Fertility and schizophrenia: evidence for increased fertility in the relatives of schizophrenic patients. Acta Psychiatrica Scandinavica 96, 260264.
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.
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.
Tannsjo T (1998). Compulsory sterilisation in Sweden. Bioethics 12, 236249.
Van Mastrigt S, Addington J, Addington D (2004). Substance misuse at presentation to an early psychosis program. Social Psychiatry and Psychiatric Epidemiology 39, 6972.
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.
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.
WHO (1992). International Statistical Classification of Diseases and Related Health Problems. World Health Organization: Geneva.
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.
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