Immune System Troubles Could Spark Behavior Woes
THURSDAY May 27, 2010 -- In the first scientific illustration of exactly how some psychiatric illnesses might be linked to an immune system gone awry, researchers report they cured mice of an obsessive-compulsive condition known as "hair-pulling disorder" by tweaking the rodents' immune systems.
Although scientists have noticed a link between the immune system and psychiatric illnesses, this is the first evidence of a cause-and-effect relationship, said the authors of a study appearing in the May 28 issue of the journal Cell. The "cure" in this case was a bone marrow transplant, which replaced a defective gene with a normal one.
The excitement lies in the fact that this could open the way to new treatments for different mental disorders, although bone marrow transplants, which can be life-threatening in themselves, are not a likely candidate, at least not at this point.
"There are some drugs already existing that are effective with respect to immune disorders," said study senior author Mario Capecchi, the recipient of a 2007 Nobel Prize in physiology or medicine.
"This is very new information in terms of there being some kind of immune reaction in the body that could be contributing to mental health symptoms," said Jacqueline Phillips-Sabol, an assistant professor of neurosurgery and psychiatry at Texas A&M Health Science Center College of Medicine and director of the neuropsychology division at Scott & White in Temple, Texas. "This helps us continue to unravel the mystery of mental illness, which used to be shrouded in mysticism. We didn't know where it came from or what caused it."
However, Phillips-Sabol was quick to point out that bone marrow transplants are not a reasonable treatment for mental health disorders.
"That's probably a stretch at least at this point," she said. "Most patients who have obsessive-compulsive disorder (OCD) are fairly successfully treated with psychotherapy."
"The story starts with a mouse mutant that has a very unusual behavior, which is very similar to the obsessive-compulsive spectrum disorder in humans called trichotillomania, when patients compulsively remove all their body hair," explained Capecchi, who is a distinguished professor of human genetics and biology at the University of Utah School of Medicine and an investigator with the Howard Hughes Medical Institute.
Some 2 percent to 3 percent of people worldwide suffer from the disorder, he said.
The same group of researchers had earlier discovered the reason for the odd behavior: these mice had changes in a gene known as Hoxb8.
To their great surprise, the gene turns out to be involved in the development of microglia, a type of immune cell found in the brain but originating in the bone marrow, whose known function is to clean up damage in the brain.
"This was strange because microglia are sort of scavengers," Capecchi explained. "If you have a stroke or bacteria or virus which destroys tissue, these cells go in and clean up the mess. But now we're saying they're involved with behavior."
When the researchers injected 10 mutant mice with bone marrow from normal mice, the mice stopped their destructive behavior and grew their hair back within three months.
When the procedure was performed in reverse, normal mice injected with abnormal Hoxb8 developed trichotillomania.
The experiment also showed that a high threshold for tolerating pain was not the cause of the disorder, as had been previously suspected.
And immune system problems have been linked with a whole range of neuropsychiatric diseases including schizophrenia, autism, Alzheimer's, bipolar disorder and obsessive-compulsive disorder, Capecchi said.
"People have always seen an association between the behavioral pathology and a defective system with respect to immune system, but nobody could figure what is happening," Capecchi said. "Are you depressed, then the immune system isn't working well, or is the immune system not working well and you're more likely to be depressed? What we're saying is that there is a direct connection between the two because the microglia derived from the bone marrow where the immune system arises [affects the OCD behavior]," he explained.
"We know a lot more about the immune system than we know about our brain," said Capecchi. "We know almost nothing about how the brain works and less about how drugs work. If we say the immune system is important, this opens up a whole new vista of things we can do simply because we know more about the immune system."
The Trichotillomania Learning Center has more about the hair-pulling disorder.
Posted: May 2010