Genetic research teams in Salt Lake City and Madison, Wis., announced last week that they have found more evidence why some people who start smoking can't seem to quit, no matter what.

Two years ago, the same teams from the University of Utah and the University of Wisconsin found out that some people just have a taste for smoking: Those who like bitter or are more tolerant to bitterness tend to like the flavor of burning tobacco.

The latest study, the results of which are published in the Public Library of Science's online journal PLoS Genetics, reveals for the first-time that those with a common genetic variation who start smoking before age 17 might well be literally built so that a habit turns into a lifelong addiction.

Those with the same genetic variation who start smoking after age 17 and even become heavy smokers as adults, quit easier and tend to stay off cigarettes at a much higher rate than those who start smoking at age 16 or younger, according to the study.

Researchers were quick to point out that discovering another genetic trait in addiction is like finding a needle in a haystack, and that they couldn't say exactly how the discovery will be put to practical use.

Only two things are known for sure, they said in interviews after making Thursday's announcement: Teen anti-smoking efforts just got science on their side; every answer research science finds raises a thousand more questions.

Nicotine dependence like any substance dependence or addition is a combination of so many complex genetic and environmental factors, said Glen Hanson, head of the Utah Addiction Center and whose job it is to translate research data into possible treatment programs or medications. "With each little revelation of what might be going on in the central nervous system, the closer we get, the more complex the whole thing appears."

The latest study might appear to reveal no more than what logic would suggest about any habit: The longer you do it, the harder it is to give up. But that observation doesn't offer much scientific evidence for what's really going on biologically.

Central to the dual research team effort is tracking how the body metabolizes nicotine. The latest clue is that for youths with a genetic variation common among European Americans, nicotine, one of the hundreds of poisonous byproducts of tobacco smoke, alters the key receptors the stimulant targets when it is metabolized. That alteration in turn sends a message in the form of a craving that becomes an abiding "need" in an individual as an adult to keep the stimulant coming.

Perhaps the brain's makeup and chemistry during human adolescence might make youths more susceptible to the effects of nicotine, said Hanson, former acting director of the National Institute on Drug Abuse.

Studies there and replicated elsewhere on human brain development show that the brain isn't physically mature or fully capable of reason until the late-20s.

"Adolescents have different cognitive abilities — risk-taking and how they see the world," Hanson said. "Among those who smoke, nicotine could also be playing a very critical role in their choices. Perhaps the biochemical and structural makeup makes them more vulnerable to the effects of nicotine. That's just one of the questions raised by the study and where the follow-up research is going to have to go."

The study results also suggest strong behavioral correlations between nicotine and mental health. Doctors and therapists working with patients who are schizophrenic, for example, report that nearly 100 percent are heavy smokers.

They or anyone who smokes or uses any substance is going for some kind of desirable effect or feeling, Hanson said.

Research at NIDA and other studies report that tobacco users say smoking helps them feel more alert or less stressed by daily activities.

Smokers aren't going after cancer or heart disease associated with it, just like alcoholics aren't going after the domestic abuse linked to drinking, he said.

Among the participants in the new study with the gene variation and who started as teens, the metabolism of nicotine likely does heighten awareness and cognition, he said.

"But they appear much more vulnerable to biological changes that will ultimately create a lifelong dependence," he said. "It's finding these little pieces of understanding that will help us ultimately understand why some people use substances, why some use and can quit, and why some can't seem to no matter what."

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