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October 22, 2009

An Infectious Problem for the Brain

by Greg Miller

As I watched a man two rows ahead of me sniffle and cough throughout a Tuesday afternoon symposium, I found myself worrying about his future mental health. After all, I'd just heard talk after talk about how immune system signaling molecules--like those triggered by infections--can muck with the brain and cause memory deficits and mood alterations.

Granted, much of this work was done with rodents. Staci Bilbo of Duke University in Durham, North Carolina, described evidence from her group suggesting that neonatal rats infected with Escherichia coli bacteria grow up to be poor performers in a standard test of rat memory. As adults, these animals have abnormally high numbers of activated microglial cells--the immune system's foot soldiers in the brain--in the hippocampus, a key memory center. Blocking microglia activation, Bilbo reported at the meeting, restores normal learning and memory.

Ruth Barrientos of the University of Colorado, Boulder, described findings from similar experiments with aging rats, suggesting that the very old as well as the very young may be particularly vulnerable to memory deficits triggered by infections and the resulting immune system activity.

Perhaps the most disturbing demonstration of the immune system's potential to influence the brain and behavior was a set of movies played by Judy Van de Water of the University of California, Davis. Van de Water is a co-investigator on a large study looking for environmental and genetic risk factors for autism. She and her colleagues have found that some mothers of autistic children have antibodies against proteins in the fetal brain. To investigate whether these antibodies could be interfering with fetal brain development, the researchers purified antibodies from human mothers of autistic children and injected them into gestating monkeys.

The movies showed the behavior of two such monkeys as adolescents. When put in a cage with another, familiar monkey, they didn't interact and play like monkeys normally do. One repeatedly ran back and forth across the floor of the enclosure. The other did backflips over and over in a corner. Although the findings are suggestive, Van de Water noted that only about 17% of moms of autistic kids in their cohort have tested positive for antibodies against fetal brain proteins. "It's certainly not what causes all autism," she said.

The most direct link to human mental health came from psychiatrist Andrew Miller of Emory University in Atlanta, who described his work with cancer patients taking immune system activating drugs to fight cancer. In 2001, Miller and colleagues reported that nearly half of people who take one such drug, interferon alfa-2b, become depressed within 12 weeks. At the meeting, Miller presented brain-imaging data suggesting that people taking interferon alfa have abnormal metabolism in several brain regions important for regulating arousal and mood. "For us in psychiatry, the idea that infection and the immune system might come into play in disorders of the brain is one of the most exciting new ideas to come down the pike in some time," Miller said.