Study Connects the Dots Between Immunity and Neurological Disorders

By AnnElise Hatjakes, M.A.

The workings of the brain and the immune system may be more closely intertwined than once thought. Dr. Paul Patterson of California Institute of Technology and his team began exploring this link ten years ago. The research team at Caltech set out to determine whether specific changes in an overactive immune system could contribute to autism-like behaviors in mice.  They found that the offspring of mice that were exposed to a viral mimic (which triggered the same immune response that an actual viral infection would) exhibited behavioral symptoms associated with autism spectrum disorder.  The results represent an important contribution to autism-related biomedical research.



According to the lab’s press release, the autism-like behaviors included “decreased social interactions and impaired communication.”  Mice whose mothers were exposed to the viral mimic  buried marbles in their cage compulsively, excessively groomed and chose to spend time alone or with a toy rather than interacting with a new mouse.  They also “vocalized ultrasonically less often or in an altered way compared to typical mice.”


This is not the first study that’s established a link between immune changes and autism.  In a phone interview, Patterson referred to a study performed in Denmark wherein researchers tracked the medical history of every person born between 1980 and 2005.  This epidemiological study found a correlation between viral infection during the first trimester of a mother’s pregnancy and a higher risk for autism spectrum disorder in her child.  A similar study conducted in Sweden showed analogous results with regard to the association between maternal infection and autism.  That study has not yet been published.  “There’s been a lot of good evidence establishing this [association] now,” Patterson said.


Patterson hopes that the results of this study may heighten awareness about the connection between neurodevelopmental disorders and the immune system.


“We’ve been pushing the involvement of the immune system [with neurological disorders] for quite a while,” Patterson said.  “I even wrote a book about it to alert scientists and also the public about the involvement of the immune system with autism, schizophrenia and depression.”  His book is entitled Infectious Behavior:  Brain-Immune Connections in Autism, Schizophrenia and Depression.


Patterson provided a common example that illustrates the effects the immune system has on behavior.  “When you get sick from an infection, you get what’s called sickness behavior.  You don’t eat or interact normally,” Patterson said.  “In animals, if you induce cytokines [signaling molecules], that will induce sickness behavior.  In clinical studies with humans, they injected people with particular cytokines, which caused depression and, in some cases, psychosis.  It’s clear from animal and human studies that cytokine can influence behavior.”


In Caltech’s study, a single immunity insult translated to autism-related behavioral abnormalities, so he suggested that women who are pregnant or plan to become pregnant should avoid infection.  “There are common sense ways of minimizing infection that we’re all familiar with but don’t do,” Patterson said.  “For instance, washing your hands carefully after going to the store or after pumping gas can help.”  He also encouraged women to avoid people who are sick even if they’re relatives or friends and wear a mask if they will be traveling on an airplane.


Knowing that immune function and neurodevelopmental disorders are connected, Patterson will now focus on ways to correct immune problems, which in turn could possibly ameliorate some of the developmental delays seen in autism.   According to the lab’s press release, “The researchers were able to correct many of the autism-like behaviors in the offspring of immune-activated mothers by giving the offspring a bone-marrow transplant from typical mice.”  The researchers emphasize that because the work was conducted on mice, the results cannot be reliably extrapolated to humans.


However, Patterson said there are other alternatives to improving immune function.  “A bone marrow transplant is not really practical,” Patterson said.  “So, we’re working on the idea of manipulating the microbiota in the gut.  The GI tract in people and animals is full of hundreds or thousands of bacteria and other microbes.  The composition of this can be manipulated by probiotics.”  Patterson said that they are currently testing this hypothesis with mice and are seeing some very good responses.


The fact that many children with autism experience gastrointestinal problems shows the link between neurodevelopmental disorders and immune functions, according to Patterson.  “Some studies say that their [GI] problems correlate with what they’re eating, but it could also have to do with their microbiome,” Patterson said.


For parents, Patterson recommends paying attention to the immune status of their child and seeing what correlates with what symptoms.  Coauthor and fellow researcher for the study Sarkis Mazmanian, a professor of biology at Caltech, has shown that gut bacteria are intimately tied to the function of the immune system.  He and Patterson are investigating whether changes to the microbiota of these mice might also influence their autism-related behaviors.