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Prenatal exposure to maternal stress and subsequent schizophrenia

The May 1940 invasion of the Netherlands

Published online by Cambridge University Press:  03 January 2018

Jim Van Os*
Department of Psychiatry and Neuropsychology, Maastricht University, The Netherlands
Jean-Paul Selten
Department of Psychiatry, University of Utrecht, The Netherlands
Dr Jim van Os, Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. Tel: 31 43 329 9783. Fax: 31 43 329 9708



It has been suggested that prenatal exposure to maternal stress increases the risk of subsequently developing schizophrenia.


The five-day invasion and defeat of The Netherlands by the German army in May 1940 constituted a severe, well-circumscribed national stressful event. Individuals exposed and non-exposed to this stressor in the first, second and third trimester of pregnancy were followed up for lifetime schizophrenia outcome through the National Psychiatric Case Register.


Cumulative incidence of schizophrenia was higher in the exposed cohort (risk ratio (RR): 1.15, 95% CI: 1.03–1.28), especially in those exposed in the first trimester (RR: 1.28, 95% CI: 1.07–1.53). Significant interaction with gender was apparent in second trimester exposed cohorts (RR men: 1.35, 95% CI: 1.05–1.74; RR women: 0.83, 95% CI: 0.61–1.12).


Maternal stress during pregnancy may contribute to the development of vulnerability to schizophrenia. The apparent longer window of exposure in male foetuses may be related to the slower pace of male early cerebral development.

Copyright © 1998 The Royal College of Psychiatrists 

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