AMSTERDAM - A famine suffered by people in the western Netherlands during the Second World War is providing a unique opportunity to examine the importance of prenatal exposures on the development of schizophrenia.
A joint effort by researchers at the University Hospital Utrecht in The Netherlands, and Columbia University in New York, aims to investigate a spike in the incidence of schizophrenia in Dutch people born in the last three months of 1945.
This cohort would have experienced their first trimester of life during the "Dutch Hunger Winter," a severe famine that occurred between October 1944 and May 1945 in The Netherlands, said Dr. Joke Kalkman, a fellow in the department of psychiatry in Utrecht.
The famine was the result of a blockade imposed by the Nazi occupation, in which the Germans banned all transport of food over inland waterways to the western part of the country, where such large cities as Amsterdam, Rotterdam and The Hague are located.
Since most foodstuffs had ready been rationed since early in the war, the situation quickly became desperate.
During the height of the famine, from February to April 1945, the population suffered a high mortality, particularly in the cities. Then abruptly, the famine was over with liberation by Allied forces in May.
"The Dutch Hunger Winter is unique because it was brief and of clearly defined duration and afflicted a population who kept excellent records on food rations during the famine, and the health outcomes both during the famine and subsequently," the researchers noted in their poster presentation here at the European Neuroscience Association meeting.
Using these records, the Columbia group had earlier published a paper looking at late outcomes in children born between 1944 and 1946. They found a spike, for example, in the incidence of neural tube defects in those born between Oct. 15 and Dec. 31, 1945, children who would have experienced their first trimester during the height of the famine. That number jumped from 1.7 per 1,000 in those born between August and October 1945, to 3.9 per 1,000 in those whose early fetal growth would have been affected by the famine.
There was a similar jump in the incidence of schizophrenia. The October-December 1945 birth cohort showed a two-fold and statistically significant increase in the risk of schizophrenia later in life.
"In other literature, there is evidence that schizophrenia is a neurodevelopmental disorder; not just genetic but also environmental factors may be important," said Dr. Kalkman in an interview.
To look more closely at the role that prenatal nutritional deficiency during the famine may have played in the etiology of schizophrenia, the researchers are conducting a case-control study. They hope to trace 20 living schizophrenia patients born during the last three months of 1945 in six cities in the western Netherlands.
One control group will include 40 age-matched controls born in the same period, who are presumably prenatally exposed to the famine who are not schizophrenic. A second group of 40 sex-matched patients with schizophrenia, born in the same cities in years previous to the famine, will also be enrolled.
For each subject, they plan to study gross brain structure and function using magnetic resonance imaging and neuropsychological testing, and ascertain any family history of psychiatric illness or obstetrical complications. Where possible, researchers hope to get a sense of the caloric and vitamin intake of the mother during famine, including any potential toxic exposures, such as eating cats or tulip bulbs.
"Tulip bulbs were eaten during the Hunger Winter," Dr. Kalkman explained. "It was the only food there was from the government, and maybe they are toxic, we don't know."
They will also look for other minor physical anomalies a neurological soft signs thought to be more common in people with neuro-developmental disorder. Dermatoglyphes, the lines on hands and feet that form in the first and second trimester of life, will also be recorded, he said. The study began in December 1994, and to date 26 cases and controls have been traced and examined with magnetic resonance imaging (MRI).
"With the first four cases we've found abnormalities in the pons and the grey matter not normally found in schizophrenia, but only in this group," he said.
There also appears to be a left-right asymmetry among the cases, with more left-handedness, Dr. Kalkman noted.
"Perhaps here, the neural tube defects, the schizophrenia, the left-handedness are neurodevelopmental disorders, and maybe through this Hunger Winter, it will be clear that to eat for a pregnant woman very important, especially in the first three months."