A study at the University of Pennsylvania School of Medicine has identifies a certain gene responsible for causing a relapse after individuals successfully bring an end to the dangerous habit of nicotine addiction. This discovery may help produce new medications to treat nicotine addiction.
The researchers have found that smokers who carry a particular version of a gene for an enzyme, which regulates dopamine in the brain, may suffer from concentration problems and other cognitive deficits when abstaining from nicotine - a problem that puts them at risk for relapse during attempts to quit smoking.
Advertisement"These findings also provide an important step toward personalized therapy for nicotine addiction by clarifying the role of inherited genetic variation in smoking abstinence symptoms that promote relapse," says senior author Caryn Lerman, the Mary W. Calkins Professor in Penn's Department of Psychiatry and Scientific Director of Penn's Abramson Cancer Center.
"The new data identify a novel brain-behavior mechanism that plays a role in nicotine dependence and relapse during quitting attempts," says James Loughead, PhD, assistant professor in the Department of Psychiatry, and lead author of the study published in the journal Molecular Psychiatry.
For their research, the team studied groups of smokers with different inherited variations in a gene that influences levels of dopamine in the prefrontal cortex, the part of the brain that governs working memory and complex decision-making.
The same research team had previously found carriers of the catechol-O-methyltransferase (COMT) val gene variant to be more susceptible to smoking relapse.
They undertook the present study with a view to determining whether smokers with the genetic background would be more likely to exhibit altered brain function and cognitive deficits during periods of abstinence from smoking.
"Inability to concentrate after quitting is reported by many patients, and this leads them to smoke to reduce these impairments," Loughead says.
In the study, 33 smokers underwent functional magnetic resonance imaging (fMRI) during periods of both abstinence from smoking and while smoking as usual.
During the brain scans, subjects were asked to hold in their minds a series of complex geometric figures. They were also asked to complete a withdrawal symptoms checklist and a questionnaire about their smoking urges.
The researchers observed that smokers with the COMT val/val genotype suffered greater deficits in working memory and brain function when they had refrained from smoking for 14 or more hours, compared to their performance on this task when they had been smoking as usual.
They revealed that such smokers also exhibited significant increases in withdrawal symptoms during the abstinence challenge session, compared to the other two genotype groups in the study.
Given the role of these indicators in relapse among smokers trying to kick the butt, the researchers believe that their findings may lead to the development of personalized therapy to treat smokers who carry the gene variant - a group that is also less responsive to existing therapies for smoking cessation.
They believe that one way could be to offer targeted therapies with drugs like COMT inhibitors to carriers of the gene.
"Given the prevalence of smoking in the population, translating these findings for medication development could have a significant clinical and public health impact," Lerman says.
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