May 21, 2012

Maternal gluten antibodies linked to schizophrenia risk in children

Babies born to women with sensitivity to gluten appear to be at increased risk for certain psychiatric disorders later in life, according to research by scientists at Karolinska Institutet in Sweden and the Johns Hopkins Children’s Center in Baltimore.

The team’s findings, published online April 25 ahead of print in the American Journal of Psychiatry, add to a growing body of evidence that many “adult” diseases may take root before and shortly after birth.

“Lifestyle and genes are not the only factors that shape disease risk, and factors and exposures before, during and after birth can help pre-program much of our adult health,” said investigator Robert Yolken, the Theodore and Vada Stanley Distinguished Professor of Neurovirology in Pediatrics at the Johns Hopkins School of Medicine. “Our study is an illustrative example suggesting that a dietary sensitivity before birth could be a catalyst in the development of schizophrenia or a similar condition 25 years later.”

Maternal infections and other inflammatory disorders during pregnancy have long been linked to greater risk for schizophrenia in the offspring, but, the Swedish and U.S. investigators say, this is the first study that points to maternal food sensitivity as a possible culprit in the development of such disorders. The findings establish a strong link but do not mean that gluten sensitivity will invariably cause schizophrenia, the investigators caution; the research, however, does suggest an intriguing new mechanism that may drive up risk and illuminate possible prevention strategies. “Our research not only underscores the importance of maternal nutrition during pregnancy and its lifelong effects on the offspring but also suggests one potential cheap and easy way to reduce risk if we were to find further proof that gluten sensitivity exacerbates or drives up schizophrenia risk,” said study lead investigator Hakan Karlsson, a neuroscientist at Karolinska Institutet and a former neurovirology fellow at Johns Hopkins.

The team’s findings are based on an examination of 764 birth records and neonatal blood samples of Swedes born between 1975 and 1985. Some 211 of the subjects subsequently developed nonaffective psychoses, such as schizophrenia and delusional disorders.

Using stored neonatal blood samples, the investigators measured levels of IgG antibodies to milk and wheat. IgG antibodies are markers of immune system reaction triggered by the presence of certain proteins. Because a mother’s antibodies cross the placenta during pregnancy to confer immunity to the baby, a newborn’s elevated IgG levels are proof of protein sensitivity in the mother. Children born to mothers with abnormally high levels of antibodies to the wheat protein gluten had nearly twice the risk of developing schizophrenia later in life, compared with children who had normal levels of gluten antibodies. The link persisted even after researchers accounted for other factors known to increase schizophrenia risk, including maternal age, gestational age, mode of delivery and the mother’s immigration status. The risk for psychiatric disorders was not increased among those with elevated levels of antibodies to milk protein.

The researchers say that the suspicion that food sensitivity in the mother can affect her child’s risk for psychiatric disorders stems from an observation made in the wake of World War II by U.S. Army researcher F. Curtis Dohan. Dohan noted that food scarcity in post-war Europe, and wheat-poor diets, led to notably fewer hospital admissions for schizophrenia. The link was merely observational, but it has piqued the curiosity of scientists ever since.

Researchers in the past also have observed that people diagnosed with schizophrenia have disproportionately high rates of celiac disease, a rare autoimmune disorder characterized by gluten sensitivity. Although it is a hallmark of the condition, gluten sensitivity alone is not enough to diagnose celiac disease. Other studies have found that some people with schizophrenia have gluten sensitivity without other signs of celiac disease, the researchers note.

Yolken and Karlsson say that the team already is conducting follow-up studies to clarify how gluten, or sensitivity to it, increases schizophrenia risk, and whether it does so only in those genetically predisposed.

Christina Dalman, of Karolinska Institutet, was the principal investigator on the research. Co-investigators were Asa Blomstrom and Susanne Wicks, both of Karolinska Institutet; and Shuojia Yang, of Johns Hopkins.

The research was funded by the Stanley Medical Research Institute, the Swedish Research Council and the City of Stockholm.

Related websites

Robert Yolken:


The study in ‘American Journal of Psychiatry’: