Prenatal exposure to maternal stress and subsequent schizophrenia. The May 1940 invasion of The Netherlands

Background: It has been suggested that prenatal exposure to maternal stress increases the risk of subsequently developing schizophrenia. Method: 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. Register Cumulative incidence of schizophrenia was higher in the exposed cohort (risk ratio (RR): 1.15, 95% Cl: 1.031.28), especially in those exposed in the first trimester (RR: 1.28, 95% Cl: 1.071.53). Significant interaction with gender was apparent in second trimester exposed cohorts (RR men: 1.35, 95% Cl: 1.05- 1.74; RR women: 0.83, 95% Cl: 0.61-1.12). Conclusion: 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.