Study of gene mutation ties schizophrenia risk to smoking

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HARTFORD — Schizophrenia is a severe mental disorder characterized by hallucinations, withdrawal from reality, and paranoia.

While there are many drugs to help treat schizophrenia, about 90 percent of people with this disease also smoke cigarettes and 68 percent of them smoke more than 25 cigarettes a day versus only 11 percent of regular smokers.

Schizophrenia is characterized by a decreased activity in the front of the brain, the prefrontal cortex, where good judgment, stress control, decision-making, and problem-solving occurs. A mutation in the CHRNA5 gene increases the risk of schizophrenia and is also linked to the prevalence of smoking. That is what human studies have found.

In a new study, researchers from the University of Colorado and the Pasteur Institute used an animal model to explore the relationship between this mutation and decreased prefrontal cortex activity and then to see if nicotine could impact that relationship. They compared mice who had the genetic mutation to those without it and found through brain imaging studies that the prefrontal cortex activity was dulled in those mice with the defect. When they introduced nicotine, they were able to partially correct this problem. So, it looks like people with schizophrenia may get actual mental benefits from smoking.

People with schizophrenia are more likely to try recreational drugs and are more prone to addictions of all kinds due to their disease. They are more likely to drink and use marijuana and illicit drugs but not nearly as much as they smoke. Smoking is expensive and increases the risk of death, heart attacks, and strokes. While the nicotine in it might help partially correct that prefrontal cortex hypoactivity, smoking induces the liver to metabolize the drugs used in schizophrenia faster than normal resulting in the need for higher doses. So smoking is not a panacea but knowing it is the nicotine instead of something else in the cigarette that is helpful, future research on nicotine patches, gum, and e-cigarettes might be helpful without causing the adverse effects of smoking and perhaps an analogue of nicotine that is not addictive can be created in the future as well.

As an aside, since smoking often precedes the onset of full-blown schizophrenic symptoms, some people worried that cigarette smoking might be a cause of schizophrenia. This might not be the case given the results of this new study in Nature Medicine. It seems more likely that pre-schizophrenic prefrontal cortex hypoactivity leads to trying substances that might be harmful and when they try cigarettes they get a perceptible benefit and continue to use it for that reason.

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 – Dr. Michael White from the UConn School of Pharmacy