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See Inside December 2007/January 2008

Smoking Away Schizophrenia?

Nicotinelike drugs show promise for alleviating cognitive impairment

Schizophrenia is famous for its symptoms of hallucinations and delusions, but sufferers also face debilitating cognitive impairment —and standard treatments with antipsychotic medications do little to compensate for intellectual loss. Seeking improved mental clarity, many patients turn to a seemingly mundane source: cigarettes. The extraordinarily high incidence of smoking in individuals with schizophrenia —about 85 percent of patients smoke compared with some 20 percent of the general population —has spurred researchers to investigate the therapeutic effects of nicotine in the diseased brain.

Every schizophrenia patient suffers some degree of deficit in memory, attention and thought organization, but no medication currently exists to treat these cognitive impairments. According to patients who smoke, cigarettes alleviate some of these symptoms, but research has found that the effect is short-lived and detrimental to overall health. The receptors to which nicotine binds in the brain quickly become desensitized, rendering smoking ultimately ineffective. And while the positive effects are disappearing, addiction is under way.

As an alternative, researchers are investigating newly derived chemical compounds that bind weakly to the brain’s nicotine receptors. Many of these binding agents are being tested in people who have schizophrenia, Alzheimer’s disease or attention-deficit hyperactivity disorder (ADHD). Although the mechanisms underlying nicotine’s cognitive effects remain unclear, scientists think it might improve focus by enhancing the brain’s ability to filter out unwanted external stimuli. Schizophrenia alters the chemical communication signals used by neurons, making it difficult for the brain to isolate a single process and devote conscious attention to it. Nicotine modifies these signaling processes and may help dampen extraneous neuronal activity.

Schizophrenia expert Carol Tamminga, professor of psychiatry at the University of Texas Southwestern Medical School, says, “Doctors like me hope that in five or 10 years we’ll have medications for different symptom domains. It’s unclear if we’re going to get medications that target specific aspects of cognition, like an attention or memory enhancer specifically, or if we’re going to get drugs that cross the board in a more global way.” But for patients, any treatment would be a welcome relief.

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