Researchers probe genetic underpinnings of nicotine addiction

December 9, 2008

A new study from the Abramson Cancer Center and Department of Psychiatry in the University of Pennsylvania School of Medicine shows that smokers who carry a particular version of a gene for an enzyme that 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. The findings, newly published in the journal Molecular Psychiatry, pave the way to identify novel medications to treat nicotine addiction.

"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, PhD, 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 lead author James Loughead, PhD, assistant professor in the Department of Psychiatry. Loughead and Lerman studied groups of smokers with different inherited variations in a gene which influences levels of dopamine in the prefrontal cortex, the part of the brain that governs working memory and complex decision-making. Spurred by their previous findings that carriers of the catechol-O-methyltransferase (COMT) val gene variant are more susceptible to smoking relapse, the Penn researchers set out to learn if smokers with this 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 this 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. Subjects were also asked to complete a withdrawal symptoms checklist and a questionnaire about their smoking urges. Results showed 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. This group also exhibited significant increases in withdrawal symptoms during the abstinence challenge session, compared to the other two genotype groups in the study.

These indicators often play a role in the reasons why smokers relapse, and therefore, may lead to the development of personalized therapy to treat smokers who carry this gene variant – a group that is also less responsive to existing therapies for smoking cessation. One method may be to offer carriers of this gene targeted therapies with drugs like COMT inhibitors, some of which have been shown to increase working memory in healthy volunteers.

"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.

Source: University of Pennsylvania

Explore further: Investigators compare effects of nicotine with and without menthol on brain and behavior

Related Stories

Investigators compare effects of nicotine with and without menthol on brain and behavior

November 16, 2017
A new study from UMass Medical School researchers at the Center for Comparative Neuroimaging explores the link between mentholated tobacco and nicotine addiction. They found that menthol administered with nicotine alters ...

Smoking study personalizes treatment

November 17, 2017
A simple blood test is allowing Vanderbilt University Medical Center (VUMC) researchers to determine which patients should be prescribed varenicline (Chantix) to stop smoking and which patients could do just as well, and ...

Vaping should be part of support to help smokers with mental health conditions quit

November 16, 2017
A group of health bodies and charities has called for more to be done to help smokers with mental health conditions quit, including accessing e-cigarettes and other treatments.

Children's exposure to secondhand smoke may be vastly underestimated by parents

November 15, 2017
Four out of 10 children in the US are exposed to secondhand smoke, according to the American Heart Association. A new Tel Aviv University study suggests that parents who smoke mistakenly rely on their own physical senses ...

E-cigarettes are more likely to be used by alcohol drinkers and former cigarette smokers

November 14, 2017
Electronic cigarettes are more frequently used by people who recently quit smoking and alcohol drinkers, according to preliminary research presented at the American Heart Association's Scientific Sessions 2017, a premier ...

E-cigarette use by high school students linked to cigarette smoking

October 30, 2017
Use of e-cigarettes by high school students was strongly associated with later cigarette smoking, according to a large study conducted in 2 Canadian provinces and published in CMAJ (Canadian Medical Association Journal).

Recommended for you

New approach to studying chromosomes' centers may reveal link to Down syndrome and more

November 20, 2017
Some scientists call it the "final frontier" of our DNA—even though it lies at the center of every X-shaped chromosome in nearly every one of our cells.

Genome editing enhances T-cells for cancer immunotherapy

November 20, 2017
Researchers at Cardiff University have found a way to boost the cancer-destroying ability of the immune system's T-cells, offering new hope in the fight against a wide range of cancers.

A math concept from the engineering world points to a way of making massive transcriptome studies more efficient

November 17, 2017
To most people, data compression refers to shrinking existing data—say from a song or picture's raw digital recording—by removing some data, but not so much as to render it unrecognizable (think MP3 or JPEG files). Now, ...

Genetic mutation in extended Amish family in Indiana protects against aging and increases longevity (Update)

November 15, 2017
The first genetic mutation that appears to protect against multiple aspects of biological aging in humans has been discovered in an extended family of Old Order Amish living in the vicinity of Berne, Indiana, report Northwestern ...

US scientists try first gene editing in the body

November 15, 2017
Scientists for the first time have tried editing a gene inside the body in a bold attempt to permanently change a person's DNA to try to cure a disease.

Genetic variant prompts cells to store fat, fueling obesity

November 13, 2017
Obesity is often attributed to a simple equation: People are eating too much and exercising too little. But evidence is growing that at least some of the weight gain that plagues modern humans is predetermined. New research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.