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