A provocative study using genetically altered mice finds a cause-and-effect link between the immune system and a psychiatric disorder.
Mario Capecchi, a Nobel Prize-winning geneticist, discovered that bone marrow transplants cure mutant mice who pull out their hair compulsively.
The study provides the first cause-and-effect link between immune system cells and mental illness, and points toward eventual new psychiatric treatments.
“We’re showing there is a direct relationship between a psychiatric disorder and the immune system, specifically cells named microglia that are derived from bone marrow” and are found in the brain, says Capecchi.
“There’s been an inference. But nobody has previously made a direct connection between the two.”
The findings – published in the journal Cell – should inspire researchers “to think about potential new immune-based therapies for psychiatric disorders,” says Capecchi, a 2007 Nobel laureate in physiology or medicine.
Capecchi and colleagues showed that pathological grooming and hair-pulling in mice – a disorder similar to trichotillomania (trick-o-til-o-MAY-nee-ah) in humans – is caused by a mutant Hoxb8 gene that results in defective microglia, which are immune system cells that originate in bone marrow and migrate from blood to the brain.
Microglia defend the brain and spinal cord, attacking and engulfing infectious agents.
Mice with pathological grooming appear to groom normally, but do so too often and for too long, leading to hair removal and self-inflicted skin wounds. The disease of pulling out head or body hair is common in humans; studies in seven international communities found trichotillomania affecting 1.9 to 2.5 of every 100 people.
In the key experiment, geneticist Shau-Kwaun Chen, Capecchi and colleagues transplanted bone marrow from normal mice into 10 mice that had a mutant Hoxb8 gene and compulsively pulled out their own chest, stomach and side fur.
As the transplant took hold during ensuing months, grooming behavior became normal, four mice recovered completely and the other six showed extensive hair growth and healing of wounds.
“A lot of people are going to find it amazing,” says Capecchi. “That’s the surprise: bone marrow can correct a behavioral defect.”
Nevertheless, “I’m not proposing we should do bone marrow transplants for any psychiatric disorder” in humans, he says.
Bone marrow transplants are expensive, and the risks and complications are so severe they generally are used only to treat life-threatening illnesses, including certain cancers and disabling autoimmune diseases such as lupus.
Capecchi says that mice with the mutant gene that causes pathological grooming now can be used to study the surprising connections between the immune system’s microglia cells and mental illness – and ultimately to produce new treatments.
“We think it’s a very good model for obsessive-compulsive disorder,” he says.