Science Watch

Almost a quarter of men and one-fifth of women in the United States smoke cigarettes, according to the American Heart Association. And although it's well-known to be a deadly habit—to the tune of around 400,000 deaths annually—more than

700,000 people a year start up. Despite multimillion-dollar antismoking campaigns targeted at children, almost all new smokers are youths.

What accounts for the glaring gap between message and behavior? New research suggests that early attitudes about smoking and early experimentation may give smoking enough of a foothold to become a lifelong addiction—and smoking may actually spur brain changes that make people resistant to antismoking messages. Add it all up and you've got a habit that's easy to start and painfully difficult to stop.

Just one puff

That's the reason early prevention is the best policy, says Joseph DiFranza, MD, an addictions researcher at the University of Massachusetts Medical School in Worcester, Mass.

His study in the May Addictive Behaviors (Vol. 33, No. 5) suggests that smoking only one cigarette can spur a loss of autonomy, which occurs when a person either has to make an effort not to smoke again or experiences discomfort when not smoking. His analysis of 30,000 teenage smokers in New Zealand, the largest study of teenage smoking to date, found that many teens reported at least minor symptoms of addiction, and those symptoms increased for every cigarette they smoked. By the time a person smokes 100 cigarettes, DiFranza says, 95 percent report addiction symptoms.

"It only takes a handful of cigarettes for the average person to become addicted," he says.

His research challenges the prevailing view that people have to smoke every day to become addicted, DiFranza says. "Kids who don't smoke every day don't consider themselves to be smokers," he says, "but they have the cravings and withdrawal symptoms."

Warning kids about the realities of addiction is a mission that Judy Andrews, PhD, shares in her lab and in her life. Andrews, a psychologist at the Oregon Research Institute in Eugene, Ore., recalls a time when her then-3-year-old daughter exclaimed, "Eww, gross!" as a smoker passed by. She knew her daughter had a decidedly negative opinion of smoking, but she wondered how children's opinions change over time.

In the 15 years since that day, Andrews has become an expert on children's feelings toward substance abuse. She's found that children as young as 7 have strong opinions about smoking, which are informed by TV, family and peers.

Andrews's latest research in the March Psychology of Addictive Behavior (Vol. 22, No. 1) suggests that these early attitudes predict whether someone becomes a smoker. She and her colleagues tested about 700 elementary school students in Oregon, second through fifth grade, by showing them images of people smoking and asking whether they thought kids who smoke are exciting, cool, neat and popular.

Seven years later, the participants who had positive social images of smoking when they were children were 30 percent to 40 percent more likely to have smoked a cigarette in the past year.

That statistic resonates with Andrews.

"I've got a teenage daughter in high school," she says, "so I take my research home." She's also taking her research to the classroom in the form of an antismoking program aimed at fifth-graders. In it, she tries to counter positive social images with negative ones, showing children unattractive pictures of people smoking and asking them, "Is this cool? Would this make you popular?" It's too early to tell how successful it will be, Andrews says, but early indications hint that children in the program indeed profess a less positive social image of smoking.

"At a young age, you can change kids' attitudes a lot easier than in 12th grade when they think they know everything," she says.

Tough habit

Yet smoking may engender changes in the brain that make smokers resistant to the very antismoking messages Andrews and her colleagues promote, according to a paper in press in Nature Neuroscience by Baylor College of Medicine neuroscientist Read Montague, PhD. His findings suggest that smokers don't learn from mistakes as well as nonsmokers.

In his research, Montague used fMRI to measure the brain activity of smokers and nonsmokers while they played an investment game with predetermined outcomes. The researchers specifically looked for two brain activity patterns known to be important to learning: experiential and fictive learning signals. Experiential learning takes place when investors adjust their behavior when their earning expectations don't match their actual earnings. Fictive learning occurs when investors compare what they actually earned with what they hypothetically would have earned had they invested differently. Together, these signals help guide decision-making in most people.

In this experiment, Montague and his colleagues teased apart these learning methods by developing algorithms to measure the impact of each signal in each betting situation. They found that although both smokers and nonsmokers learned from experiential signals, only the nonsmokers responded to the fictive signals. But when the researchers consulted the fMRI images taken throughout the study, they found that the fictive learning signals were indeed occurring in smokers' brains—they just weren't using those signals to guide their behavior.

"Both learning signals show up in the brain," Montague says, "but the smokers only use the experiential signal in making their choices."

Somewhere in their thought processes, smokers were discarding fictive learning as a decision-making strategy.

Montague suspects that the increased dopamine in the brains of smokers interferes with the reinforcement learning process that would otherwise let them learn from their mistakes, "leaving smokers guided only by immediate or experiential rewards and uninfluenced by fictive learning signals," he notes.

A surfeit of dopamine could help explain why smokers who are faced with a barrage of information about the ill effects of their habits don't up and quit, he notes.

Another suspect in the brain is the thalamus, according to a 2007 study in Neuropsychopharmacology (Vol. 32, No. 12) by psychiatry professor Jed Rose, PhD, at Duke University Medical Center.

"The thalamus is an important but incredibly neglected brain structure," Rose says.

His research into the thalamus looks to end that neglect. One of the jobs of the thalamus is to adjust the brain's responses to various stimuli, a process known as thalamic sensory gating, he explains. If the brain is getting more than it needs of some stimulus, the thalamus turns the knob down so the brain doesn't get overstimulated. Rose's study suggests that nicotine makes this process work even better, allowing the brain to block out even more of the unpleasant stimuli than normal, making the smoker calm and relaxed.

Quitting smoking, then, makes a smoker less able to cope with these stressful situations because the smoker is used to the enhanced calm provided by nicotine, the study says. They can't just light up and tune out anymore.

For these reasons and more, tobacco is "the most persistent drug of addiction," says Steven Grant, PhD, chief of the clinical neuroscience branch of the National Institute on Drug Abuse, and its cultural acceptability and legality serve to make it that much more dangerous. But understanding exactly how nicotine gains an early foothold in the brain, he says, will allow researchers to develop medicines and therapies that finally snuff it out.