Summary: A new study reports people with schizophrenia have higher levels of antibodies against Epstein-Barr virus, a herpes virus that causes mononucleosis. Researchers propose two explanations for the link to the heightened immune response to the virus: schizophrenia may alter the immune system, making patients more susceptible to EBV, or EBV may increase the risk of developing schizophrenia.
Source: Johns Hopkins University.
New research from Johns Hopkins Medicine and Sheppard Pratt Health System shows that people in the study with schizophrenia also have higher levels of antibodies against the Epstein-Barr virus (EBV), a herpes virus that causes infectious mononucleosis, so-called mono.
Researchers proposed two explanations for the association of heightened immune responses in patients with schizophrenia and EBV infection: schizophrenia might alter the immune systems of these patients and make them more susceptible to EBV, or EBV infection might increase the risk of schizophrenia.
The article was published online Nov. 20 in Schizophrenia Bulletin.
“We are interested in the role of infectious agents such as Epstein-Barr virus in schizophrenia and other serious psychiatric disorders, so we did this study to look at the associations,” said Robert Yolken, M.D., the Theodore and Vada Stanley Distinguished Professor of Neurovirology in pediatrics at Johns Hopkins Children’s Center and senior author of the study. Yolken cautioned that the study wasn’t designed to determine cause and effect.
Schizophrenia is a mental disorder where patients have distorted thinking, perception, emotions, language, sense of self and behavior. According to the World Health Organization, schizophrenia affects more than 21 million people worldwide.
While schizophrenia has some genetic associations, genes that have been found to date explain only a portion of the disease risk. Environmental exposures, including to some infectious agents, have also been identified in previous studies as increasing the risk for schizophrenia.
EBV initially causes fever and swollen lymph nodes, and is commonly transmitted through oral contact such as kissing. In severe cases, it can spread to the central nervous system and cause persistent infection. Researchers wanted to see the relationship between this EBV infection and schizophrenia.
The researchers conducted a study among 743 people — 432 with a schizophrenia diagnosis and 311 without a history of a psychiatric disorder to serve as a control group. Around 55 percent of the participants were men.
The researchers first measured levels of antibodies against components of EBV by comparing antibody levels in healthy people with those of people who have schizophrenia. They looked at the odds of having these antibodies in the 50th, 75th and 90th percentiles and found that people with schizophrenia were 1.7 to 2.3 times more likely to have increased levels of some EBV antibodies compared with people without schizophrenia.
Then they measured the antibodies to other related viruses such as varicella/chicken pox or herpes simplex type 1/cold sore virus, and didn’t find an increase of antibodies against these viruses in people with schizophrenia. These findings suggest that only EBV was associated with increased risk of schizophrenia.
After that, the researchers sequenced a portion of the participants’ DNA to determine their genetic risk for schizophrenia. Results from the analysis showed that people who had both evidence of increased genetic risk for schizophrenia and increased antibody levels to EBV had a more than eight times higher chance of being in the schizophrenia group as compared with controls. Approximately 10 percent of the individuals with schizophrenia had increased levels of both antibodies and genetic risk as compared with slightly more than 1 percent of the controls.
“We found that individuals with schizophrenia had an unusual response to Epstein-Barr virus,” said Yolken. “This indicated that the prevention and treatment of Epstein-Barr virus might represent an approach for the prevention and treatment of serious psychiatric disorders such as schizophrenia.”
Currently, there are no treatments available for EBV approved by the Food and Drug Administration, but a number of compounds that may prevent or treat replication of the virus are under investigation. The researchers considered the development of these approaches a high priority so that people with schizophrenia or other disorders associated with susceptibility to EBV could use them. In the meantime, researchers recommend preventing EBV transmission through good hygienic practices such as hand-washing and avoiding oral contact, such as kissing, with infected people.
Funding: The study is supported by the National Institute of Mental Health (MH-94268) and by the Stanley Medical Research Institute (07-1690).
Source: Vanessa McMains – Johns Hopkins University
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is adapted from the Johns Hopkins University news release.
Original Research: Abstract for “Schizophrenia is Associated With an Aberrant Immune Response to Epstein–Barr Virus” by Faith Dickerson, Lorraine Jones-Brando, Glen Ford, Giulio Genovese, Cassie Stallings, Andrea Origoni, Colm O’Dushlaine, Emily Katsafanas, Kevin Sweeney, Sunil Khushalani, and Robert Yolken in Schizophrenia Bulletin. Published November 20 2018.
Schizophrenia is Associated With an Aberrant Immune Response to Epstein–Barr Virus
Epstein–Barr virus (EBV) is a highly prevalent human herpesvirus capable of infecting the central nervous system and establishing persistent infection.
We employed solid phase immunoassay techniques to measure immunoglobulin G (IgG) class antibodies to EBV virions and defined proteins in 432 individuals with schizophrenia and 311 individuals without a history of a psychiatric disorder. Western blot testing was performed to document reactivity to specific EBV proteins. Polygenic risk for schizophrenia was calculated from genome sequencing arrays. Levels of antibodies between the groups were compared by multivariate analyses incorporating clinical, genetic, and demographic measures.
Individuals with schizophrenia had marked elevations in the levels of antibodies to EBV virions as compared to the control population. Further analyses indicated increased levels of reactivity to EBV-viral capsid antibody (VCA) but not to EBV nuclear antigen-1 (EBNA-1) or to other human herpesviruses. Western blot analysis confirmed increased reactivity to VCA proteins in the group of individuals with schizophrenia and documented a lack of increased levels of antibodies to EBNA-1. Genetic analyses indicated an additive effect of increased levels of antibodies to EBV virions and genetic susceptibility to schizophrenia, with individuals with elevated levels of both type of markers having a greater than 8.5-fold odds of a schizophrenia diagnosis.
Individuals with schizophrenia have increased levels of antibodies to some but not all EBV proteins indicating an aberrant response to EBV infection. This aberrant response may contribute to the immunopathology of schizophrenia and related disorders.