The Dutch famine and schizophrenia spectrum disorders.

In the Dutch Hunger Winter at the end of World War II a combination of circumstances created the conditions of a natural experiment. Unlike other famines, the Dutch famine struck at a precisely circumscribed time and place, and in a society able to document the timing and severity of the nutritional deprivation as well as the effects on fertility and health. Because the Dutch maintained comprehensive military and health records, it was possible to compare the incidence of neurodevelopmental disorders in adulthood for birth cohorts exposed versus those unexposed to prenatal famine. We have conducted several studies guided by the hypothesis that prenatal micronutrient deficiencies can cause neurodevelopmental schizophrenia or related personality disorders. In this paper we shall summarize our previous work and combine the outcome data of the different studies. Early prenatal famine was found to be specifically and robustly associated with each of three conditions: (1) congenital anomalies of the central nervous system, (2) schizophrenia, and (3) schizophrenia spectrum personality disorders. We found that the greatest increase in the risk of schizophrenia spectrum disorder- schizophrenia plus spectrum personality disorder- occurred among males born in the famine cities in December 1945 (relative risk = 2.7; 95% confidence interval = 1.5-5.1). Persons born in December 1945 were generally conceived at the absolute peak of the famine (March-April 1945). In the hope that the associations we have found may offer clues to the aetiology of schizophrenia, we are currently tracing and examining the cases of schizophrenia after prenatal exposure to famine.