Smoking May Improve Cognitive Deficits in Schizophrenic Patients, Yale Researchers Find

When schizophrenic patients quit smoking, some aspects of their cognitive function become impaired, according to a new study published this month by Yale researchers in the Journal Neuropsychopharmacology.

The researchers found that cigarette smoking improves a type of cognitive function called visuospatial working memory (VSWM) in patients with schizophrenia, but that smoking had no beneficial effects, or even negative effects, on this form of cognitive function in healthy subjects without schizophrenia.

“This is one of only a few studies to suggest that nicotine has a beneficial effect on spatial working memory, which is known to be impaired in schizophrenic patients,” said principal investigator Tony P. George, M.D., assistant professor of psychiatry at Yale School of Medicine and the Connecticut Mental Health Center.

“The question still remains whether nicotine can improve VSWM in non-smoking schizophrenic patients, who, based on our results have even worse spatial working memory function compared to smoking schizophrenics,” George added. “Proving this may be difficult due to ethical concerns about giving nicotine to non-smokers, given its addictive properties.”

It is well known among researchers that patients with schizophrenia have high rates of cigarette smoking compared to the general population. Past animal studies have shown that nicotine has complex effects on spatial working memory, with most showing that nicotine improves it. George said schizophrenic patients might be smoking as a form of self-medication to alleviate cognitive dysfunction linked to low activity of the neurotransmitter dopamine in the prefrontal cortex (PFC), a part of the brain that is known to be abnormal in schizophrenics and may in part mediate performance on spatial working memory tasks. Since nicotine is known to increase dopamine levels in the PFC, cigarette smoking may normalize PFC dopamine levels, and improve spatial working memory deficits in these patients.

Using medications that help smokers quit, George and his team examined the effects of up to 10 weeks of smoking abstinence on a computerized test of this cognitive function (VSWM). They tested 23 schizophrenic patients and 29 non-schizophrenic subjects, all of whom were dependent on cigarettes. They also examined VSWM function in eight non-smoking schizophrenic patients and 16 control subjects as a comparison to test the effects of smoking status on this cognitive function.

George said ongoing studies might eventually lead to the development of novel nicotine-like drugs that may improve cognitive dysfunction in schizophrenics, but without the health risks of tobacco smoking. Such nicotine receptor-stimulating drugs could eventually become potential new treatments for cognitive dysfunction in schizophrenia and other psychiatric disorders.

George recently received a three-year, $625,000 National Institute on Drug Abuse grant to continue his research in this area. With this new grant, he and his team are using a controlled human laboratory study to investigate the effects of overnight smoking cessation, and then resuming smoking on several aspects of cognitive dysfunction in schizophrenic patients, and in comparison to non-psychiatric smokers. An investigational drug that blocks brain nicotine receptors is used to demonstrate that the ability of smoking to enhance cognition is due to stimulation of brain nicotine receptors. Preliminary results from this new study confirm the findings of this paper.

In addition to George, other authors on this study include Jennifer Vessicchio, research associate; Angelo Termine and Tom Pepper, research assistants; Deanna Sahady and Cory Head, Yale undergraduate students; Thomas R. Kosten, M.D., professor of psychiatry; and Bruce E. Wexler, M.D., professor of psychiatry.