Brain Circuit Overloaded in Schizophrenics

In people with schizophrenia, a brain circuit that regulates emotion is swamped with a chemical messenger called dopamine. The new finding confirms a longstanding hypothesis about schizophrenia and offers the most direct evidence so far about why schizophrenics lose touch with reality.

The devastating symptoms of schizophrenia include delusions, hallucinations, and paranoia. Since every effective antipsychotic drug blocks a receptor for the neurotransmitter dopamine, researchers guessed more than 30 years ago that dopamine circuits were overactive in people with the disease. That could be caused by excess dopamine, too many dopamine receptors, or both. Indeed, autopsies of schizophrenics showed an overabundance of a type of dopamine receptors in the striatum, a part of the brain that helps regulate emotion. But because most schizophrenics have been treated with antipsychotic drugs, some researchers argued that was a result of drug treatment rather than the disease.

To measure whether dopamine-sensitive circuits were overly active in schizophrenics, Anissa Abi-Dargham of Columbia University College of Physicians and Surgeons in New York City and her colleagues compared 18 schizophrenics with 18 normal subjects. First they treated patients and controls for 2 days with a drug that bumps dopamine off its receptors. Then, they gave patients a radioactively tagged mimic of dopamine that could accumulate on the emptied dopamine receptors. Using a brain-imaging method called single-photon computerized emission tomography, they compared the amount of dopamine-like molecules docked on the receptors in the two groups.

In people with schizophrenia, the amount of dopamine-like molecules bound to receptors increased twice as much as in control subjects, they report in the 5 July issue of the Proceedings of the National Academy of Sciences. This most likely means that the schizophrenics have both more dopamine available and more dopamine receptors. What's more, the increase occurred in both the 10 chronic patients--who had used antipsychotic medication in the past--and in the eight newly diagnosed patients who had never been treated with drugs.

The research "can potentially help us understand how antipsychotic medications are working," says psychiatrist and neuroscientist Francine Benes of Harvard Medical School in Boston. But psychiatrist Shitij Kapur of the University of Toronto cautions that researchers still need a way to measure dopamine directly in the brain of living schizophrenics. But "assuming this holds up," he says, "the entire [dopamine] story will start to come together."

For more information about schizophrenia from the National Institute of Mental Health: