Drug-induced discovery sheds light on mental illness

Schizophrenia Update, January 2004

21 November 2003

Schizophrenia affects the brain's chemistry and structure

A single molecule may underpin the psychotic symptoms of schizophrenia, a mouse study suggests. A better understanding of the roots of the disease and new antipsychotic medications may follow.

Three main chemical messengers, called neurotransmitters, are implicated. Different researchers tend to favour one molecule the others as the disease's root cause.

"This study shows that all three schools of thought could be correct," says Paul Greengard of Rockefeller University, New York, who led the work.

Greengard's team treated mice with the mind-altering drugs amphetamine, LSD or PCP - also known as angel dust. Each drug specifically targets one of the suspect neurotransmitter systems, but has similar effects on brain and behaviour.

Each hallucinogen altered the same mystery brain protein, DARPP-32, the team found1. Animals developed schizophrenic symptoms - in mice, this involves repetitive grooming and nervousness.

The cause of the neurotransmitter imbalance is still a mystery. But the finding suggests that all three chemicals might influence DARPP-32, in turn causing schizophrenia.

Schizophrenia a complex disease that affects the brain's chemistry and structure, says Carol Tamminga from the University of Texas, Dallas, who studies the disorder. "The next step is to work out how a molecular change like this translates into hallucinations and delusions," she says.

Drug lead

The finding may aid the production of new schizophrenia therapies. Mice lacking DARPP-32 were immune to the drugs' psychotic effects, the team found.

Current therapies damp down one neurotransmitter called dopamine. Delusions subside but attention and memory problems often persist, and serious adverse effects are common.

The finding may also lead to improved animal models of schizophrenia. Mice with abnormal DARPP-32 might better mimic the brain chemistry and behaviour of human patients than drug-treated animals, says Tamminga.

Svenningsson, P. et al. Diverse psychotomimetics act through a common signalling pathway. Science, 302, 1412 - 1415, (2003). |Link|



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