Nobel winner links mental illness to immune system defect

Washington, May 28 (IANS) A Nobel Prize-winning geneticist has discovered the first ever link between immune system cells and psychiatric disorder, which potentially opens the way to 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 Mario Capecchi, professor of human genetics at the University of Utah School of Medicine (UUSM).

‘There’s been an inference. But nobody has previously made a direct connection between the two,’ said 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 in humans – is caused by a mutant Hoxb8 gene that results in defective microglia.

Microglia are immune system cells that originate in bone marrow and migrate from blood to the brain. They 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 behaviour 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 behavioural 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, said an UUSM release.

‘We think it’s a very good model for obsessive-compulsive disorder,’ says Capecchi. The researchers also transplanted bone marrow into normal mice from Hoxb8 mutant, hair-pulling mice. The normal mice started pulling out their hair compulsively.

Normal mice transplanted with normal bone marrow kept grooming normally, while mutant mice implanted with mutant bone marrow exhibited severe grooming and self-mutilation. Half died, probably due to difficulty in re-establishing mutant bone marrow.

These findings were published in the Friday issue of Cell.