Association between maternal exposure to toxoplasmosis and increased risk for developing schizophrenia

A study published last month in the American Journal of Psychiatry suggests an association between maternal exposure to toxoplasmosis and increased risk for developing schizophrenia in adult children.

The study, which evaluated archived blood samples from pregnant women who participated in a large birth cohort called the Child Health and Development Study (CHDS) from 1959–1967, was conducted by researchers at the New York State Psychiatric Institute and the Department of Epidemiology at the Mailman School of Public Health at Columbia University, in collaboration with the Kaiser Permanente Medical Care Plan, Northern California Region.

Toxoplasmosis is a parasitic infection that can develop from eating undercooked meat and unwashed fruits and vegetables, drinking contaminated water, or not washing one's hands after gardening or changing cat litter boxes. Researchers found a potential link between high maternal toxoplasmosis gondii antibody titers and development of schizophrenia spectrum disorders in the adult offspring. No association was found for moderate antibody titers. While active toxoplasmosis infection is known to adversely affect fetal brain development, this is the first suggestion of a possible association between an elevated maternal antibody to toxoplasmosis and the risk of schizophrenia.

"These findings underscore the value of prenatal serologic samples to document how maternal infectious disease exposures affect the development of adult disorders over time," said Alan Brown, MD, lead author and associate professor of clinical psychiatry and epidemiology at the New York State Psychiatric Institute, Columbia University and Mailman School of Public Health. Since publication of this study, another group presented similar findings at a recent scientific conference. Their study, based in Denmark, also suggests a potential link between elevated levels of maternal toxoplasmosis gondii antibody and increased risk for schizophrenia among adult offspring. Dr. Brown noted, "While it's as good an idea as ever to wash hands before eating and to cook meat thoroughly, these studies are too preliminary to lead to new public health recommendations."

The risk of schizophrenia spectrum disorders in the general population is about one percent. The increase related to high toxoplasma antibody suggested by the Columbia study would add another one to two percent to this risk.

"Evidence from this and previous studies leads us to consider that the increased risk for schizophrenia may not stem from exposure to a specific infectious disease, but from a mechanism secondary to infection, such as inflammation," said Ezra Susser, MD, DrPH, Anna Cheskis Gelman and Murray Charles Gelman Professor and chair of the Department of Epidemiology at the Mailman School of Public Health. Dr. Susser is also senior investigator of the Prenatal Determinants of Schizophrenia (PDS) study, and head of Epidemiology of Brain Disorders at the New York State Psychiatric Institute. He added, "The current findings, while intriguing, must be replicated in a larger sample before we can conclude that elevated toxoplasma antibody in a pregnant woman could predispose her unborn child to develop schizophrenia later in life."

The PDS study is based in the Child Health and Development Study (CHDS) cohort initiated by Jacob Yerushalmy at the University of California, Berkeley, in 1959, in collaboration with Kaiser Permanente Medical Care Plan in Northern California (KPNC). The goal of the CHDS was to examine influences on outcomes of pregnancy and childhood health and development. The CHDS recruited nearly every pregnant woman under obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California. The 19,044 offspring of these women born between 1959 and 1967 were automatically enrolled in KFHP. In addition to collecting and storing blood sera samples, the CHDS study collected extensive data on the prenatal period, and conducted maternal interviews on family health history, maternal and paternal health habits, and maternal and paternal socio-demographic information. In 1997- 1999, the research team used electronic databases to identify adult CHDS offspring that might have developed schizophrenia during the period between January 1, 1981 and December 31, 1997. These individuals were invited to participate in a diagnostic interview, and those who participated and were confirmed to have schizophrenia or disorders in the schizophrenia spectrum, were then compared with carefully matched individuals from the CHDS who did not develop these disorders.

In August 2004, the researchers determined in the same cohort that prenatal exposure to influenza may increase the risk for schizophrenia years later. Both of these findings are part of the larger team PDS study, which examines prenatal infection, nutrition, chemical exposure, paternal age, and a range of other prenatal factors that influence schizophrenia risk.

The PDS research is one of a number of "life course studies" being overseen by Dr. Susser at the Mailman School. In addition to the CHDS study, Dr. Susser and his team are looking at large birth cohorts from the U.S., Israel, and Norway to observe the pathogenesis of chronic and acute diseases and their links to prenatal and postnatal exposure to environmental factors such as viruses and toxins.