Yale Bulletin and Calendar

July 21, 2000

Volume 28, Number 35

Study reveals why most
schizophrenics are heavy smokers

A study conducted by Yale researchers suggests that nicotine enhances the cognitive functions of the brain and may explain why many schizophrenics are heavy smokers.

"Almost all patients with schizophrenia are smokers," says Dr. Tony George, assistant professor of psychiatry at the School of Medicine. "Our study shows there may be a mechanistic link to explain the high rates of association between schizophrenia and nicotine addiction, and maybe drug addiction in general."

George, lead author of the study published recently in the journal of Neuropsychopharmacology, said previous studies found that nicotine stimulates the dopamine or "reward" pathway in subcortical areas of the brain. The subcortical dopamine system underlies addictive properties of drugs of abuse and is also involved in allowing a person to feel pleasure from activities such as eating and sex.

"Schizophrenics have some propensity to have an abnormal drive in the reward pathway that make them susceptible to addictive and other risky behaviors," says George.

George and his colleagues wanted to determine if the brain's endogenous opioid pathways, which are responsive to nicotine, also regulate the cortical, or higher functioning, dopamine pathways to the brain, as well as the subcortical pathways.

"We found that nicotine works to increase cognitive function through the cortical dopamine pathway by activating the endogenous opiate system," George says. "The implication is that this could tie together drug reward pathways in the brain and those pathways thought to be abnormal in patients with schizophrenia," he says. "A major part of schizophrenia involves problems with cognitive functions such as memory, judgment, reason and the ability to focus. These functions are dependent on the frontal cortex of the brain and the frontal cortical dopamine pathways. Schizophrenic patients have cognitive dysfunction related, in part, to abnormalities in the cortical dopamine pathway, and cigarette smoking may improve cognitive problems in these patients by stimulating cortical dopamine function."

The finding was made through tests on an animal model in which rats were administered nicotine and the opiate receptor antagonist naloxone. Naloxone blocks endogenous opiate systems.

"We found that nicotine can have cognitive enhancing effects while giving naloxone could block these effects of nicotine," George says. "The question now is whether opioid receptor drugs could have therapeutic value for schizophrenia and in the treatment of nicotine addiction."

-- By Jacqueline Weaver

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