Biomedical Frontiers: Winter/Spring 1996, Vol.3, No.2
Research Advance: Famine Linked to Schizophrenia

More than 50 years after the fact, a Nazi blockade of the Netherlands is providing evidence that a mother's nutritional status during pregnancy may be connected with her offspring's risk of developing schizophrenia.

Dr. Ezra Susser, associate professor of clinical psychiatry and epidemiology at Columbia and NYSPI, and colleagues used food rationing and health outcomes records kept by the Dutch during the so-called Hunger Winter and for decades afterward to arrive at their findings. The Hunger Winter occurred from October 1944 to early May 1945, when the Nazis established a blockade in retaliation for the Dutch underground's support of an Allied invasion (the invasion was the subject of the movie "A Bridge Too Far"). The blockade resulted in a severe famine, the peak of which occurred during the last three months. Using the dates of birth to estimate the dates of conception, Dr. Susser found that individuals who were conceived during the last three months of the famine had twice the risk of developing schizophrenia as individuals conceived either in the early months of the famine or after it ended.

At the peak of the famine, malnutrition was the leading cause of mortality, and fertility rates were down 50 percent. Typical rations for the period were well below 1,000 calories a day, consisting of a potato, a piece of bread, and a sugar beet. In addition to attempting to supplement these rations with food from the black market, people ate tulip bulbs or put paper in their soup.

"The study could turn out to have important preventive implications for at least some forms of schizophrenia," says Dr. Susser. "The most likely explanation is that a nutritional deficiency is involved, perhaps of a micronutrient." Dr. Susser compares the current state of knowledge about schizophrenia and nutrition to recent research that confirmed that folic acid deficiencies in early gestation can cause neural tube defects. "Until recently we knew very little about the causes of neural tube defects, except that they run in families-which is similar to what we know now about schizophrenia. But then a series of observations began to link neural tube defects to prenatal nutritional deficiency. After only a few decades of work, we now know for sure that we can reduce the risk of neural tube defects by providing folic acid supplements in early pregnancy."

A pilot study headed by Dr. Susser is now examining the relationship between prenatal levels of folate and schizophrenia. Funded by the National Alliance for Research on Schizophrenia and Depression, the Prenatal Determinants of Schizophrenia study will examine a birth cohort of 12,000 individuals, all born at the Kaiser Permanente Hospital in Oakland, Calif., between 1959 and 1966. Columbia researchers will examine frozen blood samples-which include blood samples taken from women during various stages of their pregnancies-to correlate levels of micronutrients in the mothers with any later development of schizophrenia in their offspring. In addition, the researchers will search for a connection between schizophrenia and prenatal exposure to the flu. Previous studies have found a connection between exposure in mid-gestation to an influenza epidemic and an increased risk of schizophrenia. Dr. Hans W. Hoek of the Netherlands collaborated in the Dutch Hunger Winter investigation. The study was based on data collected by Dr. Zena Stein and Dr. Mervyn Susser, Dr. Ezra Susser's parents, who demonstrated in 1974, in their landmark book on the Dutch famine, that prenatal starvation in early pregnancy caused preterm birth, excess infant deaths up to three months, and excess obesity in young adults.