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Diet and lifestyle

Major study links parasite in cat excrement to schizophrenia

A large-scale study has linked infection with the Toxoplasma gondii parasite (toxoplasmosis) to an increased risk of developing schizophrenia. The study is the first to examine the relationship between when people develop toxoplasmosis and when they develop schizophrenia.

Twenty-five percent of Danes are infected with a parasite that spends most of its life in the intestines of cats. However, Toxoplasma gondii can infect other animals, including humans, monkeys and mice. This occurs through contact with the parasite, which is present in is cat excrement.

Toxoplasma gondii has developed some pretty clever ways to get from mice into cats. It alters the chemical signals in mice brains so they are no longer afraid of the smell of cat urine. The cats can then catch the mice much more easily, and the parasites can enter their favourite host. The parasite also affects the brains of monkeys so they are not afraid of the smell of leopard urine.

A new Danish study shows that the parasite can also affect humans. Unfortunately, people with toxoplasmosis have a greater risk of developing schizophrenia.

“Toxoplasmosis is the reason why pregnant women should avoid changing too many cat litter boxes, because the parasite can infect their fetus and cause brain damage. Several previous small studies have linked toxoplasmosis to an increased risk of mental disorders, which this large-scale study confirms,” explains Kristoffer Sølvsten Burgdorf, postdoctoral fellow, Department of Clinical Immunology, Rigshospitalet, Copenhagen.

The new study was recently published in Brain, Behavior and Immunity.

Toxoplasmosis increases the risk of developing schizophrenia

The researchers wanted to definitively determine whether toxoplasmosis is associated with developing schizophrenia.

They did this by linking the blood samples from 82,000 people in the Danish Blood Donor Study with Denmark’s health registries, which contain data on people’s mental disorders and other diseases and causes of death.

Among the 82,000 blood samples, the researchers selected 11,500 and measured the presence of antibodies expressed by the body’s immune response to toxoplasmosis. Then they examined whether the people with these antibodies in their blood had a higher risk of having been diagnosed with schizophrenia.

The study showed that toxoplasmosis increased the risk of schizophrenia by 50%.

“We found that significantly more participants with toxoplasmosis had schizophrenia than those who were not infected. If the risk of developing schizophrenia is slightly less than 1%, toxoplasmosis increases the risk of developing schizophrenia to 1.5%,” explains Kristoffer Sølvsten Burgdorf.

Toxoplasmosis may actually increase the risk of schizophrenia by 300%

The result confirmed previous studies, but the new study featured an examination of how the development of toxoplasmosis and the development of schizophrenia are associated over time.

“The problem is that we cannot determine whether people had developed schizophrenia before they developed toxoplasmosis by simply linking the measurements of antibodies in the blood and the presence of schizophrenia,” says Kristoffer Sølvsten Burgdorf.

By examining the dataset in greater detail, the researchers found a subset of participants who had not been diagnosed with schizophrenia when they were included in the study. All these participants were analysed to determine whether they had toxoplasmosis.

The researchers examined which participants developed schizophrenia during the study period and discovered a much stronger association between toxoplasmosis and the risk of developing schizophrenia. In fact, the increase in risk was 300%, with the absolute risk of schizophrenia increasing from about 1% to 3%.

“This is the first time anyone has found this association, and it is very strong,” explains Kristoffer Sølvsten Burgdorf.

No vaccine against toxoplasmosis

The discovery is important because billions of people worldwide have toxoplasmosis, which may therefore have caused many cases of schizophrenia. Nevertheless, Kristoffer Sølvsten Burgdorf does not want to paint too bleak a picture.

Instead, he sees an obvious opportunity to delve deeper into the subject and carry out more research on what exactly happens when a parasite causes a mental disorder. In addition to schizophrenia, toxoplasmosis may be linked to an increased risk of other mental disorders, including depression.

In addition, Kristoffer Sølvsten Burgdorf advocates caution in warning about the possible danger of developing a mental disorder when toxoplasmosis cannot be prevented or treated yet.

“We have no vaccines or treatments for toxoplasmosis, and we should be careful about saying that cats are dangerous before we know more,” says Kristoffer Sølvsten Burgdorf.

Using the discovery to learn more about schizophrenia

Instead of overreacting, Kristoffer Sølvsten Burgdorf views the discovery as an obvious opportunity to find out more about schizophrenia.

By studying how toxoplasmosis affects the brain and thereby increases the risk of developing schizophrenia, the researchers can learn much more about the mechanisms behind schizophrenia.

Understanding schizophrenia better may improve treatment.

In this context, a study monitoring both the development of toxoplasmosis and the development of schizophrenia over time is unique.

“This type of study can only be done in Denmark, because we have such good data from both the Danish Blood Donor Study and from the health registries. In the Danish Blood Donor Study, we obtained blood samples from the same people over many years, and if we can find biomarkers in the blood that change over time among people who develop schizophrenia, we may learn much more about it,” explains Kristoffer Sølvsten Burgdorf.

Kristoffer recently submitted an application for a grant. He plans to delve deeper into this aspect if he receives funding.

Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders” has been published in Brain, Behavior and Immunity. Several co-authors are employed at the Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Denmark.

Kristoffer Sølvsten Burgdorf
Postdoc
The Brunak Group aims for understanding multi-morbidity disease progression patterns and their relation to treatment events. The group integrates heterogeneous life science data from the molecular and clinical domains and is also engaged in methodology of translational utility, such as techniques of relevance within precision medicine. The Brunak Group has specific interest in genes and proteins, which play a role in several diseases, genes that may rationalize clinically observed patterns of multi-morbidity, or be of interest in relation to treatment strategies in the domain of chronic pathology. The group aims for discriminating between treatment-related disease correlations and other comorbidities, stratifying patients not only from their genotype but also on phenotypic data from resources such as clinical descriptions in electronic medical records. “Together with our secure supercomputing infrastructure, that is designed to handle population-wide data from Denmark and other countries, our goal is to complement classical epidemiology towards disease-spectrum wide analyses in a lifelong perspective, that can take events separated by long time periods into account,” says Professor and Group Leader Søren Brunak. The human genome, proteome variation and personalized medicine are themes with a strong focus in the group. In particular the ranking of treatment options and the reduction of patient-specific adverse drug reactions. Data integration and machine learning methods development in the big biomedical data domain is a major theme, as is the design of supercomputing infrastructure and private cloud solutions needed for person-sensitive data integrity.