Rodent of the Week: A link between the immune system and mental illness

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Little is known about the causes of severe mental illnesses. Genes and environmental factors are thought to contribute. But more specific biological processes, still not yet clear, probably contribute to brain dysfunction that results in hallucinations, psychosis and compulsive behavior.

A clue from a study with mice has emerged that links mental illness, particularly obsessive-compulsive disorder, with immune system processes. Mario Capecchi, a distinguished professor of genetics at the University of Utah, found that mutant mice who pull out their hair compulsively (a condition similar to trichotillomania in humans and a model for mental illness in mice) were cured of their abnormal behavior when they received bone marrow transplants. The study was published online Thursday in the journal Cell.

The mice who groom compulsively, thus pulling out their hair, carry a mutant Hoxb8 gene. Capecchi transplanted normal bone marrow from mice into 10 Hoxb8 mutant mice. Four recovered from their abnormal grooming behavior and six improved. It’s not clear why the treatment worked. But cells called microglia are derived from bone marrow, and these same cells are found in the brain. It could be that microglia make substances called cytokines that activate or inhibit nerve cells and influence behavior. Or, microglia might play a role in nerve-signal transmissions. Nevertheless, the connection between the two is worth further investigation, Capecchi said. ‘That’s the surprise: Bone marrow can correct a behavioral defect,’ he said.

The research is preliminary, however, said Capecchi, who shared the 2007 Nobel Prize in physiology/medicine for developing a way to knock out genes in mice in order to analyze gene function. People with mental illness should not try bone marrow transplants as a cure. The compulsive grooming syndrome in mice can’t be considered the equivalent of obsessive-compulsive disorder in humans, said Dr. Steven E. Hyman, a professor of neurobiology at Harvard Medical School, in an editorial accompanying the study.

‘Analysis of Hoxb8 mutant mice should help to illuminate such matters as the role of different populations of microglia in the brain,’ Hyman said. ‘Moreover, these mice could give rise to sorely needed new hypotheses about the mechanisms underlying human disorders characterized by compulsive behaviors.’

-- Shari Roan