Inflamed. Brain tissue shows that immune cells called microglia (stained blue) are more active in people with autism.

Autism Associated With Brain Inflammation

Many things are a bit off in the brains of people with autism. In early childhood, for example, such brains grow faster than normal, and as they mature, key neural circuitry apparently doesn't get hooked up. Now researchers have found evidence that immune cells are more active in autistic brains--causing increased inflammation--and remain that way for much of life. Although the cells involved are normally important for proper brain development and function, it's not clear whether this inflammation is a cause--or a result--of autism.

Previous studies of the immune system in autism have focused on observable aspects outside the brain, such as antibodies for measles. A team led by neurologist Carlos Pardo and his postdoc, Diana Vargos, at Johns Hopkins School of Medicine and colleagues has now looked at tissue from the brains of seven people with autism, aged 5 to 44 years, and seven brain autopsy samples from nonautistic people.

By staining the tissue for proteins involved in immune reactions, they found that immune cells, called microglia and astroglia, in the brain tissue from autistic people had been much more active than those in the control brains. This was true in three regions that are normally affected in autism: the frontal cortex, cingulate gyrus, and cerebellum. The most severe changes were in the cerebellum, the researchers report in the 15 November Annals of Neurology; this region is typically characterized by loss of Purkinje cells, which integrate information. Other signs of inflammation included heightened levels of inflammatory signaling molecules, called chemokines and cytokines.

The team also looked at the immune system of six living people with autism. The cytokine levels in their cerebrospinal fluid were also elevated compared to controls. Some studies have suggested that MCP-1 and other cytokines are important for protecting neurons, so it may be that the brain is attempting to repair itself, Pardo says. The team suggests that cytokine levels in the cerebrospinal fluid might one day be used to assist in diagnosis of autism. There are no drugs available that lessen the innate inflammation of the brain; even if there were, they might end up interfering with the protective aspect, the researchers caution.

"It's a very provocative, interesting finding, but the interpretation is wide open," says child neurologist Isabelle Rapin, who studies autism at the Mount Sinai School of Medicine in New York City. The immune reaction is puzzling, she notes, given the lack of obvious neuropathology; there's nothing in autistic brains like the plaques in Alzheimer's patients, for example. Given the preliminary nature of the work, Rapin says it will take much more study before cytokines can be used to diagnose the disease.

Related sites
Groovy PowerPoint presentation on microglia
Carlos Pardo's Web site