Chronic smokers have biological changes in the brain similar to those caused by antidepressant drugs, according to a study gaining national attention.

The finding possibly explains an added difficulty in smoking cessation as well as a reason for the high rate of smoking among people with depression, said University of Mississippi Medical Center (UMC) scientists in Jackson who led the study.

The three-year study funded by the National Institute of Mental Health was published in the Archives of General Psychiatry's September issue.

"What our study demonstrates for the first time is that chronic smoking produces biological changes in the human brain that are antidepressant-like," said Dr. Gregory A. Ordway, the study's principal investigator. The lead author and collaborator is Dr. Violetta Klimek. He is a professor and she is an assistant professor in UMC's Department of Psychiatry and Human Behavior.

The investigators said the biological changes probably are not caused by the nicotine in tobacco alone, if at all. It appears that a compound produced when tobacco burns causes the changes in the brain; that compound probably includes a nitrate, they said.

The overall study involved 20 human cadaver brains, including 10 from smokers and 10 from non-smokers. The published study covered a total of 16 brains.

The scientists examined a lower, posterior portion of the brain that is associated with depression, the locus coeruleus. None of the subjects had been diagnosed with depression in their lifetimes, so that was not a factor, Ordway added.

The study found that the brains of chronic smokers had neurochemical abnormalities in the locus coeruleus that can be produced by repeatedly treating laboratory animals with antidepressant drugs, he explained.

Specifically, long-term smoking appears to inhibit monoamine oxidase (or acts as an MAO inhibitor). Monoamine oxidase is the enzyme that metabolizes monoamines -- such as norepinephrine, dopamine and serotonin, Klimek explained. The locus coeruleus produces norepinephrine. Drugs that inhibit monoamines are antidepressants.

Nicotine, Ordway added, does have antidepressant qualities, but is not an MAO inhibitor.

It's uncertain whether chronic smokers have these brain characteristics before they start smoking, which could increase their susceptibility to becoming smokers. But Ordway said investigators suspect smoking itself causes the neurochemical changes.

Future UMC research will include studies to find out. Another study underway at UMC is evaluating the effects of smokeless vs. smoked tobacco on brain monoamines.

The brain collection is at Case Western Reserve University in Cleveland, Ohio, which shares the samples with UMC in a cooperative program.

Other investigators in the study were UMC's Dr. Craig A. Stockmeier, a professor of psychiatry who coordinates the brain bank; Dr. Meng-Yang Zhu, a senior research associate in psychiatry; and Dr. Warren L. May, an assistant professor of medicine. Four other investigators are from Case Western.

---University of Mississippi Medical Center

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