Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-25T10:12:03.497Z Has data issue: false hasContentIssue false

Prenatal Factors in the Pathogenesis of Schizophrenia

Published online by Cambridge University Press:  06 August 2018

Matti O. Huttunen*
Affiliation:
Department of Psychiatry, University of Helsinki, and Mental Health Research Unit, National Health Institute, Helsinki
Ricardo A. Machon
Affiliation:
Department of Psychology, Loyola Marymount University, Los Angeles
Sarnoff A. Mednick
Affiliation:
Social Science Research Institute, University of Southern California, Los Angeles, USA
*
Kolmas linja 20 B 21, 00530 Helsinki, Finland

Abstract

The excess of winter–spring births among individuals suffering from schizophrenia provides strong evidence for the existence of some prenatally occurring factors in the pathogenesis of schizophrenia. Recent epidemiological findings suggest that maternal viral infections during the second trimester of pregnancy may play a crucial role in the aetiology of adult schizophrenia. A ‘two-hit window’ hypothesis of the mechanism of action of prenatal factors in the pathogenesis of schizophrenia suggests at least two time-specific prenatal aetiological events. The observed association between prenatal viral infection and increased incidence of adult schizophrenia need not be a direct cytotoxic result of the viral infection, but may be caused indirectly, for example from foetal minor cerebral haemorrhages produced by the anticoagulant effects of aspirin.

Type
Research Article
Copyright
Copyright © 1994 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Barr, C. E., Mednick, S. A. & Munk-Jorgensen, P. (1990) Exposure to influenza epidemics during gestation and adult schizophrenia: a 40-year study. Archives of General Psychiatry, 47, 869874.CrossRefGoogle ScholarPubMed
Berner, P. (1991) Delusional atmosphere. British Journal of Psychiatry, 159 (suppl. 14), 8893.CrossRefGoogle Scholar
Bogerts, B. & Falkai, P. (1991) Clinical and neurodevelopmental aspects of brain pathology in schizophrenia. In Developmental Neuropathology of Schizophrenia (eds Mednick, S. A., Cannon, T. D., Barr, C. E., et at), pp. 93120. New York: Plenum Press.Google Scholar
Bowler, A. E. & Torrey, E. F. (1990) Influenza and schizophrenia. Archives of General Psychiatry, 47, 876877.Google Scholar
Bracha, H. S., Torrey, E. F., Bigelow, L. B., et al (1991) Subtle signs of prenatal maldevelopment of the hand ectoderm in schizophrenia: a preliminary monozygotic twin study. Biological Psychiatry, 30, 719725.CrossRefGoogle ScholarPubMed
Bracha, H. S., Torrey, E. F., Gottesman, I. I, et al (1992) Second-trimester markers of fetal size in schizophrenia: a study of monozygotic twins. American Journal of Psychiatry, 149, 13551361.Google Scholar
Cannon, T. D. (1991) The possible neurodevelopmental significance of structural imaging findings in schizophrenia. In Developmental Neuropathology of Schizophrenia (eds Mednick, S. A., Cannon, T. D., Barr, C. E., et al), pp. 149166. New York: Plenum Press.Google Scholar
Cannon, T. D., Mednick, S. A. & Parnas, J. (1990) Antecedents of predominantly negative and predominantly positive symptom schizophrenia in a high-risk population. Archives of General Psychiatry, 47, 622632.Google Scholar
Conrad, A. J. & Scheibel, A. B. (1987) Schizophrenia and the hippocampus: the embryological hypothesis extended. Schizophrenia Bulletin, 13, 577587.CrossRefGoogle ScholarPubMed
Cutting, J. (1991) Delusional misidentification and the role of the right hemisphere in the appreciation of identity. British Journal of Psychiatry, 159 (suppl. 14), 7075.Google Scholar
Der, G., Gupta, S. & Murray, R. M. (1990) Is schizophrenia disappearing? Lancet, 335, 513516.Google Scholar
Dykes, K. L., Mednick, S. A., Cannon, T. D., et al (1991) Obstetrical events and adult schizophrenia. In Developmental Neuropathology of Schizophrenia (eds Mednick, S. A., Cannon, T. D., Barr, C. E., et al), pp. 121140. New York: Plenum Press.Google Scholar
Garver, D. L. (1989) Schizophrenia spectrum. Current Opinion in Psychiatry, 2, 2934.Google Scholar
Granroth, G. (1978) Defects of the central nervous system in Finland: III. Diseases and drugs in pregnancy. Early Human Development, 2, 147162.Google Scholar
Guy, J. D., Majorski, L. V., Wallace, C. J., et al (1983) The incidence of minor physical anomalies in adult male schizophrenics. Schizophrenia Bulletin, 9, 571582.Google Scholar
Hakosalo, J. K. & Saxen, L. (1971) Influenza epidemic and congenital defects. Lancet, ii, 13461347.CrossRefGoogle Scholar
Hamilton, W. J., Boyd, J. D. & Mossman, H. W. (1972) Human Embryology: Prenatal Development of Form and Function, pp. 567646. Cambridge: Heffer.CrossRefGoogle Scholar
Hare, E. (1988) Temporal factors and trends, including birth seasonality and the viral hypothesis. In Handbook of Schizophrenia, Vol. 3 (eds Tsuang, M. T. & Simpson, J. C.), pp. 345377. Amsterdam: Elsevier.Google Scholar
Harjulehto, T., Aro, T. & Saxen, L. (1988) Long-term changes in medication during pregnancy. Teratology, 37, 145148.Google Scholar
Huttunen, M. O. (1989) Maternal stress during pregnancy and the behavior of the offspring. In Early Influences Shaping the Individual (ed. Doxiadis, S.), pp. 175182. New York: Plenum Press.CrossRefGoogle Scholar
Huttunen, M. O. & Niskanen, P. (1978) Prenatal loss of father and psychiatric disorders. Archives of General Psychiatry, 35, 429431.CrossRefGoogle ScholarPubMed
Kendell, R. E. & Kemp, I. W. (1989) Maternal influenza in the etiology of schizophrenia. Archives of General Psychiatry, 46, 878882.Google Scholar
Kullander, A., Källen, B. & Sandahl, B. (1976) Exposure to drugs and other possibly harmful factors during the first trimester of pregnancy. Acta Obstetricia and Gynecologica Scandinavica, 55, 395405.Google Scholar
LaFosse, J. M. & Mednick, S. A. (1991) A neurodevelopmental approach to schizophrenia research. In Developmental Neuropathology of Schizophrenia (eds Mednick, S. A., Cannon, T. D., Barr, C. E., et al), pp. 221225. New York: Plenum Press.Google Scholar
Lyon, M. & Barr, C. E. (1991) Possible interactions of obstetrical complications and abnormal fetal brain development in schizophrenia. In Fetal Neural Development and Adult Schizophrenia (eds Mednick, S. A., Cannon, T. D., Barr, C. E., et al), pp. 134149. New York: Cambridge University Press.Google Scholar
Machon, R. A., Mednick, S. A. & Schulsinger, F. (1983) The interaction of seasonality, place of birth, genetic risk and subsequent schizophrenia in a high risk sample. British Journal of Psychiatry, 143, 383388.Google Scholar
McNeil, T. F. (1988) Obstetric factors and perinatal injuries. In Handbook of Schizophrenia, Vol. 3 (eds Tsuang, M. T. & Simpson, J. C.), pp. 319344. Amsterdam: Elsevier.Google Scholar
Mednick, S. A., Machon, R. A., Huttunen, M. O., et al (1988) Adult schizophrenia following prenatal exposure to an influenza epidemic. Archives of General Psychiatry, 45, 189192.CrossRefGoogle Scholar
Mednick, S. A., Huttunen, M. O. & Machon, R. A. (1994) Prenatal influenza infections and adult schizophrenia. Schizophrenia Bulletin (in press) Nowakowski, R. S. (1987) Basic concepts of CNS development. Child Development, 58, 568595.Google Scholar
O'Callaghan, E., Sham, P., Takei, N., et al (1991) Schizophrenia after prenatal exposure to 1957 A2 influenza epidemic. Lancet, 337, 12481250.CrossRefGoogle ScholarPubMed
Otake, M. & Schull, W. I. (1984) In utero exposure to A-bomb radiation and mental retardation: a reassessment. British Journal of Radiology, 57, 409414.Google ScholarPubMed
Sham, P. C., O'Callaghan, E., Takei, N., et al (1992) Schizophrenia following pre-natal exposure to influenza epidemic between 1939 and 1960. British Journal of Psychiatry, 160, 461466.CrossRefGoogle ScholarPubMed
Torrey, E. F. (1989) Schizophrenia: fixed incidence or fixed thinking. Psychological Medicine, 19, 285287.Google Scholar
Torrey, E. F. & Kaufmann, (1986) Schizophrenia and neuroviruses. In Handbook of Schizophrenia, Vol. 1 (eds Nasrallah, H. A. & Weinberger, D. R.), pp. 361376. Amsterdam: Elsevier.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.