NARSAD Grant-Funded Research Finds Maternal Infection May Increase Risk of Schizophrenia in Offspring

Albert H.C. Wong, M.D., Ph.D., Expert on schizophrenia
Albert Wong, M.D., Ph.D.

Researchers are devoting increasing attention to the possible effects of the immune system in the causation of brain and behavior disorders. Among them is a team of neuroscientists at the Centre for Addiction and Mental Health at the University of Toronto. Albert H.C. Wong, M.D., Ph.D., used his 2010 NARSAD Independent Investigator Grant to lead a Canadian team in work that was published May 1st in The Journal of Neuroscience. The team demonstrated that activation in mice of an expectant mother’s immune system––which simulates the effects of infection––can, in certain circumstances, lead to the birth of offspring with “exacerbated schizophrenia-related behaviors.”  

The published studies were performed in mice genetically engineered to bear two variants of mutations in a gene called DISC1. Mutations in DISC1 have repeatedly been shown in animal and human studies to be associated with substantially increased risk for schizophrenia. Drs. Tatiana V. Lipina and Wong were joined in the work by John C. Roder, Ph.D., a 2006 NARSAD Distinguished Investigator Grantee and Clement Zai, Ph.D., a 2012 NARSAD Young Investigator Grantee. The team treated these mice, at high risk for producing offspring with schizophrenia, with a chemical that mimics the impact of a virus and activates the mouse’s immune system.

Pups born of these immune-activated high-risk mothers had exacerbated versions of symptoms, both cognitive and social, seen in human schizophrenia. When similar, expecting mouse-moms with activated immune systems were also given an antibody that blocked the action of a pro-inflammatory molecule called Interleukin-6 (IL-6), schizophrenia-related behaviors were not seen in the offspring. “Maternal infection during pregnancy is common, but not all offspring of infected mothers develop schizophrenia,” the scientists cautioned. What their study does show, they say, is the “maternal immune activation must interact with [risk] genes to produce psychiatric illness.”

Read the study abstract

Article comments

There are increasing evidences that favor the prenatal beginning of schizophrenia. These evidences point toward intra-uterine environmental factors that act specifically during the second pregnancy trimester producing a direct damage of the brain of the fetus. The current available technology doesn't allow observing what is happening at cellular level since the human brain it is not exposed to a direct analysis in that stage of the life. In 1977 we began a direct research of the brain of fetuses of schizophrenic mothers in order to finding differences at cellular level in relation to controls. In these studies we have observed within the nuclei of neurons the presence of complete and incomplete viral particles that reacted in positive form with antibodies to herpes simplex hominis type I [HSV1] virus, and mitochondria alterations. The importance of these findings can have practical applications in the prevention of the illness keeping in mind its direct relation to the aetiology and physiopathology of schizophrenia. A study of amniotic fluid cells in women at risk of having a schizophrenic offspring is considered. Of being observed the same alterations that those observed previously in the cells of the brain of the studied foetuses, it would intend to these women in risk of having a schizophrenia descendant, previous information of the results, the voluntary medical interruption of the pregnancy or an early anti HSV1 viral treatment as preventive measure of the later development of the illness.

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