Effects of Family History and Place and Season of Birth on the Risk of Schizophrenia
Preben Bo Mortensen, D.M.Sc., Carsten Bøcker Pedersen, M.Sc., Tine Westergaard, M.D., Jan Wohlfahrt, M.Sc., Henrik Ewald, D.M.Sc., Ole Mors, Ph.D., Per Kragh Andersen, D.M.Sc., and Mads Melbye, D.M.Sc.
Background Although a family history of schizophrenia is thebest-established risk factor for schizophrenia, environmentalfactors such as the place and season of birth may also be important.
Methods Using data from the Civil Registration System in Denmark,we established a population-based cohort of 1.75 million personswhose mothers were Danish women born between 1935 and 1978.We linked this cohort to the Danish Psychiatric Central Registerand identified 2669 cases of schizophrenia among cohort membersand additional cases among their parents.
Results The respective relative risks of schizophrenia for personswith a mother, father, or sibling who had schizophrenia were9.31 (95 percent confidence interval, 7.24 to 11.96), 7.20 (95percent confidence interval, 5.10 to 10.16), and 6.99 (95 percentconfidence interval, 5.38 to 9.09), as compared with personswith no affected parents or siblings. The risk of schizophreniawas associated with the degree of urbanization of the placeof birth (relative risk for the capital vs. rural areas, 2.40;95 percent confidence interval, 2.13 to 2.70). The risk wasalso significantly associated with the season of birth; it washighest for births in February and March and lowest for birthsin August and September. The population attributable risk was5.5 percent for a history of schizophrenia in a parent or sibling,34.6 percent for urban place of birth, and 10.5 percent forthe season of birth.
Conclusions Although a history of schizophrenia in a parentor sibling is associated with the highest relative risk of havingthe disease, the place and season of birth account for manymore cases on a population basis.
Source Information
From the Department of Psychiatric Demography, Institute for Basic Psychiatric Research, Psychiatric Hospital, Aarhus University Hospital, Risskov (P.B.M., H.E., O.M.), and the Department of Epidemiology Research, Danish Epidemiology Science Center, Statens Serum Institut, Copenhagen (C.B.P., T.W., J.W., P.K.A., M.M.) both in Denmark.
Address reprint requests to Dr. Mortensen at the Department of Psychiatric Demography, Institute for Basic Psychiatric Research, Psychiatric Hospital, Aarhus University Hospital, Skovagervej 2, 8240 Risskov, Denmark, or at ph.ph1.pbm{at}aaa.dk.
Risk Factors for Schizophrenia
McGuffin P., Gottesman I. I., Swerdlow R. H., Binder D., Parker W. D., Weilerstein R., Mortensen P. B., Pedersen C. B., Ewald H.
Extract |
Full Text
N Engl J Med 1999;
341:370-372, Jul 29, 1999.
Correspondence
This article has been cited by other articles:
McGrath, J., Saha, S., Chant, D., Welham, J.
(2008). Schizophrenia: A Concise Overview of Incidence, Prevalence, and Mortality. Epidemiol Rev
30: 67-76
[Abstract][Full Text]
March, D., Hatch, S. L., Morgan, C., Kirkbride, J. B., Bresnahan, M., Fearon, P., Susser, E.
(2008). Psychosis and Place. Epidemiol Rev
30: 84-100
[Abstract][Full Text]
Mittal, V. A., Ellman, L. M., Cannon, T. D.
(2008). Gene-Environment Interaction and Covariation in Schizophrenia: The Role of Obstetric Complications. Schizophr Bull
34: 1083-1094
[Abstract][Full Text]
Brown, A. S., Susser, E. S.
(2008). Prenatal Nutritional Deficiency and Risk of Adult Schizophrenia. Schizophr Bull
34: 1054-1063
[Abstract][Full Text]
van Os, J., Rutten, B. P., Poulton, R.
(2008). Gene-Environment Interactions in Schizophrenia: Review of Epidemiological Findings and Future Directions. Schizophr Bull
34: 1066-1082
[Abstract][Full Text]
Welham, J., Isohanni, M., Jones, P., McGrath, J.
(2008). The Antecedents of Schizophrenia: A Review of Birth Cohort Studies. Schizophr Bull
0: sbn084v1-sbn084
[Abstract][Full Text]
Werner, S., Malaspina, D., Rabinowitz, J.
(2007). Socioeconomic Status at Birth Is Associated With Risk of Schizophrenia: Population-Based Multilevel Study. Schizophr Bull
33: 1373-1378
[Abstract][Full Text]
WEISER, M., VAN OS, J., REICHENBERG, A., RABINOWITZ, J., NAHON, D., KRAVITZ, E., LUBIN, G., SHMUSHKEVITZ, M., KNOBLER, H. Y., NOY, S., DAVIDSON, M.
(2007). Social and cognitive functioning, urbanicity and risk for schizophrenia. Br. J. Psychiatry
191: 320-324
[Abstract][Full Text]
McGrath, J. J.
(2007). The Surprisingly Rich Contours of Schizophrenia Epidemiology. Arch Gen Psychiatry
64: 14-16
[Full Text]
Al-Uzri, M. M., Reveley, M. A., Owen, L., Bruce, J., Frost, S., Mackintosh, D., Moran, P. M.
(2006). Measuring memory impairment in community-based patients with schizophrenia: Case-control study. Br. J. Psychiatry
189: 132-136
[Abstract][Full Text]
Nicolson, S. E., Mayberg, H. S., Pennell, P. B., Nemeroff, C. B.
(2006). Persistent Auditory Hallucinations That Are Unresponsive to Antipsychotic Drugs. Am. J. Psychiatry
163: 1153-1159
[Full Text]
Stefansson, C.-G.
(2006). Chapter 5.5: Major public health problems -- mental ill-health. Scand J Public Health
34: 87-103
Pedersen, C. B., Mortensen, P. B.
(2006). Are the Cause(s) Responsible for Urban-Rural Differences in Schizophrenia Risk Rooted in Families or in Individuals?. Am J Epidemiol
163: 971-978
[Abstract][Full Text]
SALIB, E., CORTINA-BORJA, M.
(2006). Effect of month of birth on the risk of suicide. Br. J. Psychiatry
188: 416-422
[Abstract][Full Text]
Eaton, W. W., Byrne, M., Ewald, H., Mors, O., Chen, C.-Y., Agerbo, E., Mortensen, P. B.
(2006). Association of Schizophrenia and Autoimmune Diseases: Linkage of Danish National Registers. Am. J. Psychiatry
163: 521-528
[Abstract][Full Text]
Kirkbride, J. B., Fearon, P., Morgan, C., Dazzan, P., Morgan, K., Tarrant, J., Lloyd, T., Holloway, J., Hutchinson, G., Leff, J. P., Mallett, R. M., Harrison, G. L., Murray, R. M., Jones, P. B.
(2006). Heterogeneity in Incidence Rates of Schizophrenia and Other Psychotic Syndromes: Findings From the 3-Center AeSOP Study.. Arch Gen Psychiatry
63: 250-258
[Abstract][Full Text]
McGrath, J. J
(2006). Variations in the Incidence of Schizophrenia: Data Versus Dogma. Schizophr Bull
32: 195-197
[Abstract][Full Text]
ALLARDYCE, J., GILMOUR, H., ATKINSON, J., RAPSON, T., BISHOP, J., McCREADIE, R. G.
(2005). Social fragmentation, deprivation and urbanicity: relation to first-admission rates for psychoses. Br. J. Psychiatry
187: 401-406
[Abstract][Full Text]
Krabbendam, L., van Os, J.
(2005). Schizophrenia and Urbanicity: A Major Environmental Influence--Conditional on Genetic Risk. Schizophr Bull
31: 795-799
[Abstract][Full Text]
Wicks, S., Hjern, A., Gunnell, D., Lewis, G., Dalman, C.
(2005). Social Adversity in Childhood and the Risk of Developing Psychosis: A National Cohort Study. Am. J. Psychiatry
162: 1652-1657
[Abstract][Full Text]
Haargaard, B., Wohlfahrt, J., Rosenberg, T., Fledelius, H. C., Melbye, M.
(2005). Risk Factors for Idiopathic Congenital/Infantile Cataract. IOVS
46: 3067-3073
[Abstract][Full Text]
Frank, O., Giehl, M., Zheng, C., Hehlmann, R., Leib-Mosch, C., Seifarth, W.
(2005). Human Endogenous Retrovirus Expression Profiles in Samples from Brains of Patients with Schizophrenia and Bipolar Disorders. J. Virol.
79: 10890-10901
[Abstract][Full Text]
St Clair, D., Xu, M., Wang, P., Yu, Y., Fang, Y., Zhang, F., Zheng, X., Gu, N., Feng, G., Sham, P., He, L.
(2005). Rates of Adult Schizophrenia Following Prenatal Exposure to the Chinese Famine of 1959-1961. JAMA
294: 557-562
[Abstract][Full Text]
Qin, P.
(2005). Suicide risk in relation to level of urbanicity--a population-based linkage study. Int J Epidemiol
34: 846-852
[Abstract][Full Text]
Maki, P., Veijola, J., Jones, P. B., Murray, G. K., Koponen, H., Tienari, P., Miettunen, J., Tanskanen, P., Wahlberg, K.-E., Koskinen, J., Lauronen, E., Isohanni, M.
(2005). Predictors of schizophrenia--a review. Br Med Bull
73-74: 1-15
[Abstract][Full Text]
Li, J., Laursen, T. M., Precht, D. H., Olsen, J., Mortensen, P. B.
(2005). Hospitalization for Mental Illness among Parents after the Death of a Child. NEJM
352: 1190-1196
[Abstract][Full Text]
Cantor-Graae, E., Selten, J.-P.
(2005). Schizophrenia and Migration: A Meta-Analysis and Review. Am. J. Psychiatry
162: 12-24
[Abstract][Full Text]
van Os, J., Pedersen, C. B., Mortensen, P. B.
(2004). Confirmation of Synergy Between Urbanicity and Familial Liability in the Causation of Psychosis. Am. J. Psychiatry
161: 2312-2314
[Abstract][Full Text]
Leask, S. J.
(2004). Environmental influences in schizophrenia: the known and the unknown. Adv. Psychiatr. Treat.
10: 323-330
[Abstract][Full Text]
Brenner, A. V., Linet, M. S., Shapiro, W. R., Selker, R. G., Fine, H. A., Black, P. M., Inskip, P. D.
(2004). Season of birth and risk of brain tumors in adults. Neurology
63: 276-281
[Abstract][Full Text]
Abel, K. M.
(2004). Foetal origins of schizophrenia: testable hypotheses of genetic and environmental influences. Br. J. Psychiatry
184: 383-385
[Full Text]
Eaton, W., Mortensen, P. B., Agerbo, E., Byrne, M., Mors, O., Ewald, H.
(2004). Coeliac disease and schizophrenia: population based case control study with linkage of Danish national registers. BMJ
328: 438-439
[Full Text]
Mortensen, P. B., Pedersen, C. B., Melbye, M., Mors, O., Ewald, H.
(2003). Individual and Familial Risk Factors for Bipolar Affective Disorders in Denmark. Arch Gen Psychiatry
60: 1209-1215
[Abstract][Full Text]
Gunnell, D., Rasmussen, F., Fouskakis, D., Tynelius, P., Harrison, G.
(2003). Patterns of Fetal and Childhood Growth and the Development of Psychosis in Young Males: A Cohort Study. Am J Epidemiol
158: 291-300
[Abstract][Full Text]
McGrath, J. J.
(2003). Invited Commentary: Gaining Traction on the Epidemiologic Landscape of Schizophrenia. Am J Epidemiol
158: 301-304
[Full Text]
Byrne, M., Agerbo, E., Ewald, H., Eaton, W. W., Mortensen, P. B.
(2003). Parental Age and Risk of Schizophrenia: A Case-control Study. Arch Gen Psychiatry
60: 673-678
[Abstract][Full Text]
Aleman, A., Kahn, R. S., Selten, J.-P.
(2003). Sex Differences in the Risk of Schizophrenia: Evidence From Meta-analysis. Arch Gen Psychiatry
60: 565-571
[Abstract][Full Text]
Jablensky, A. V., Kalaydjieva, L. V.
(2003). Genetic Epidemiology of Schizophrenia: Phenotypes, Risk Factors, and Reproductive Behavior. Am. J. Psychiatry
160: 425-429
[Full Text]
van Os, J., Hanssen, M., Bak, M., Bijl, R. V., Vollebergh, W.
(2003). Do Urbanicity and Familial Liability Coparticipate in Causing Psychosis?. Am. J. Psychiatry
160: 477-482
[Abstract][Full Text]
CANTOR-GRAAE, E., PEDERSEN, C. B., McNEIL, T. F., MORTENSEN, P. B.
(2003). Migration as a risk factor for schizophrenia: a Danish population-based cohort study. Br. J. Psychiatry
182: 117-122
[Abstract][Full Text]
Chumakov, I., Blumenfeld, M., Guerassimenko, O., Cavarec, L., Palicio, M., Abderrahim, H., Bougueleret, L., Barry, C., Tanaka, H., La Rosa, P., Puech, A., Tahri, N., Cohen-Akenine, A., Delabrosse, S., Lissarrague, S., Picard, F.-P., Maurice, K., Essioux, L., Millasseau, P., Grel, P., Debailleul, V., Simon, A.-M., Caterina, D., Dufaure, I., Malekzadeh, K., Belova, M., Luan, J.-J., Bouillot, M., Sambucy, J.-L., Primas, G., Saumier, M., Boubkiri, N., Martin-Saumier, S., Nasroune, M., Peixoto, H., Delaye, A., Pinchot, V., Bastucci, M., Guillou, S., Chevillon, M., Sainz-Fuertes, R., Meguenni, S., Aurich-Costa, J., Cherif, D., Gimalac, A., Van Duijn, C., Gauvreau, D., Ouellette, G., Fortier, I., Raelson, J., Sherbatich, T., Riazanskaia, N., Rogaev, E., Raeymaekers, P., Aerssens, J., Konings, F., Luyten, W., Macciardi, F., Sham, P. C., Straub, R. E., Weinberger, D. R., Cohen, N., Cohen, D.
(2002). Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. Proc. Natl. Acad. Sci. USA
99: 13675-13680
[Abstract][Full Text]
GUNNELL, D., HARRISON, G., RASMUSSEN, F., FOUSKAKIS, D., TYNELIUS, P.
(2002). Associations between premorbid intellectual performance, early-life exposures and early-onset schizophrenia: Cohort study. Br. J. Psychiatry
181: 298-305
[Abstract][Full Text]
SCULLY, P. J., QUINN, J. F., MORGAN, M. G., KINSELLA, A., O'CALLAGHAN, E., OWENS, J. M., WADDINGTON, J. L.
(2002). First-episode schizophrenia, bipolar disorder and other psychoses in a rural Irish catchment area: incidence and gender in the Cavan--Monaghan study at 5 years. Br. J. Psychiatry
181
: s3-s9
[Abstract][Full Text]
BYRNE, M., AGERBO, E., MORTENSEN, P. B.
(2002). Family history of psychiatric disorders and age at first contact in schizophrenia: an epidemiological study. Br. J. Psychiatry
181
: s19-s25
[Abstract][Full Text]
Goff, D. C.
(2002). A 23-Year-Old Man With Schizophrenia. JAMA
287: 3249-3257
[Full Text]
FRIEDLANDER, A. H., MARDER, S. R.
(2002). The psychopathology, medical management and dental implications of schizophrenia. Journal of the American Dental Association
133: 603-610
[Abstract][Full Text]
Kustner, B. M., Varo, C. R., Gonzalez, F. T.
(2002). The Goals and Method of the Andalusian Case Register for Schizophrenia. Int J Soc Psychiatry
48: 47-57
[Abstract]
Pedersen, C. B., Mortensen, P. B.
(2001). Evidence of a Dose-Response Relationship Between Urbanicity During Upbringing and Schizophrenia Risk. Arch Gen Psychiatry
58: 1039-1046
[Abstract][Full Text]
DALMAN, C., THOMAS, H. V., DAVID, A. S., GENTZ, J., LEWIS, G., ALLEBECK, P.
(2001). Signs of asphyxia at birth and risk of schizophrenia: Population-based case--control study. Br. J. Psychiatry
179: 403-408
[Abstract][Full Text]
ALLARDYCE, J., BOYDELL, J., VAN OS, J., MORRISON, G., CASTLE, D. J., MURRAY, R. M., McCREADIE, R. G.
(2001). Comparison of the incidence of schizophrenia in rural Dumfries and Galloway and urban Camberwell. Br. J. Psychiatry
179: 335-339
[Abstract][Full Text]
HARRISON, G., GUNNELL, D., GLAZEBROOK, C., PAGE, K., KWIECINSKI, R.
(2001). Association between schizophrenia and social inequality at birth: case--control study. Br. J. Psychiatry
179: 346-350
[Abstract][Full Text]
van Os, J., Hanssen, M., Bijl, R. V., Vollebergh, W.
(2001). Prevalence of Psychotic Disorder and Community Level of Psychotic Symptoms: An Urban-Rural Comparison. Arch Gen Psychiatry
58: 663-668
[Abstract][Full Text]
PEDERSEN, C. B., MORTENSEN, P. B.
(2001). Family history, place and season of birth as risk factors for schizophrenia in Denmark: a replication and reanalysis. Br. J. Psychiatry
179: 46-52
[Abstract][Full Text]
Karlsson, H., Bachmann, S., Schroder, J., McArthur, J., Torrey, E. F., Yolken, R. H.
(2001). From the Cover: Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia. Proc. Natl. Acad. Sci. USA
98: 4634-4639
[Abstract][Full Text]
Buckland, P. R.
(2001). Genetic association studies of alcoholism -- problems with the candidate gene approach. Alcohol Alcohol
36: 99-103
[Abstract][Full Text]
Poulton, R., Caspi, A., Moffitt, T. E., Cannon, M., Murray, R., Harrington, H.
(2000). Children's Self-Reported Psychotic Symptoms and Adult Schizophreniform Disorder: A 15-Year Longitudinal Study. Arch Gen Psychiatry
57: 1053-1058
[Abstract][Full Text]
Weickert, T. W., Goldberg, T. E., Gold, J. M., Bigelow, L. B., Egan, M. F., Weinberger, D. R.
(2000). Cognitive Impairments in Patients With Schizophrenia Displaying Preserved and Compromised Intellect. Arch Gen Psychiatry
57: 907-913
[Abstract][Full Text]
Rhoades, D. R.
(2000). Schizophrenia: A Review for Family Counselors. The Family Journal
8: 258-266
[Abstract]
Narita, K., Sasaki, T., Akaho, R., Okazaki, Y., Kusumi, I., Kato, T., Hashimoto, O., Fukuda, R., Koyama, T., Matsuo, K., Okabe, Y., Nanko, S., Hohjoh, H., Tokunaga, K.
(2000). Human Leukocyte Antigen and Season of Birth in Japanese Patients With Schizophrenia. Am. J. Psychiatry
157: 1173-1175
[Abstract][Full Text]
McGlashan, T. H., Hoffman, R. E.
(2000). Schizophrenia as a Disorder of Developmentally Reduced Synaptic Connectivity. Arch Gen Psychiatry
57: 637-648
[Abstract][Full Text]
EISENBERG, L.
(2000). Is psychiatry more mindful or brainier than it was a decade ago?. Br. J. Psychiatry
176: 1-5
[Full Text]
Westergaard, T., Mortensen, P. B., Pedersen, C. B., Wohlfahrt, J., Melbye, M.
(1999). Exposure to Prenatal and Childhood Infections and the Risk of Schizophrenia: Suggestions From a Study of Sibship Characteristics and Influenza Prevalence. Arch Gen Psychiatry
56: 993-998
[Abstract][Full Text]
McGuffin, P., Gottesman, I. I., Swerdlow, R. H., Binder, D., Parker, W. D., Weilerstein, R., Mortensen, P. B., Pedersen, C. B., Ewald, H.
(1999). Risk Factors for Schizophrenia. NEJM
341: 370-372
[Full Text]