Christine Sheffer, associate medical professor at CCNY’s Sophie Davis School of Biomedical Education, tracked smokers from different socioeconomic backgrounds after they had completed a statewide smoking cessation program in Arkansas.

Whether rich or poor, participants managed to quit at about the same rate upon completing a program of cognitive behavioral therapy, either with or without nicotine patches. But as time went on, a disparity between the groups appeared and widened.

Those with the fewest social and financial resources had the hardest time staving off cravings over the long run.  “The poorer they are, the worse it gets,” said Professor Sheffer, who directed the program and was an assistant professor with the University of Arkansas for Medical Sciences at the time.

She found that smokers on the lowest rungs of the socioeconomic ladder were 55 percent more likely than those at the upper end to start smoking again three months after treatment. By six months post-quitting, the probability of their going back to cigarettes jumped to two-and-a-half times that of the more affluent smokers. The research will be published in the March 2012 issue of the “American Journal of Public Health” and will appear ahead-of-print online under the journal’s “First Look” section.

In their study, Professor Sheffer and her colleagues noted that overall, Americans with household incomes of $15,000 or less smoke at nearly three times the rate of those with incomes of $50,000 or greater. The consequences are bleak. “Smoking is still the greatest cause of preventable death and disease in the United States today,” noted Professor Sheffer. “And it’s a growing problem in developing countries.”

Harder to Stay Away

Professor Sheffer suggested reasons it may be harder for some to give up tobacco forever.

Smoking relieves stress for those fighting nicotine addiction, so it is life’s difficulties that often make them reach for the cigarette pack again. Unfortunately, those on the lower end of the socioeconomic scale suffer more hardships than those at the top – in the form of financial difficulties, discrimination, and job insecurity, to name a few. And for those smokers who started as teenagers, they may have never learned other ways to manage stress, said Professor Sheffer.

For people with lower socioeconomic status (SES), it can be tougher to avoid temptation as well. “Lower SES groups, with lower paying jobs, aren’t as protected by smoke-free laws,” said Sheffer, so individuals who have quit can find themselves back at work and surrounded by smokers. Also fewer of them have no-smoking policies in their homes.

These factors are rarely addressed in standard treatment programs. “The evidence-based treatments that are around have been developed for middle-class patients,” Professor Sheffer pointed out. “So (in therapy) we talk about middle-class problems.”

Further research would help determine how the standard six sessions of therapy might be altered or augmented to help. “Our next plan is to take the results of this and other studies and apply what we learned to revise the approach, in order to better meet the needs of poor folks,” she said. “Maybe there is a better arrangement, like giving ‘booster sessions’. Not everybody can predict in six weeks all the stresses they will have later on down the road.”

“Some people say [quitting] is the most difficult thing in their life to do,” said Sheffer. “If we better prepare people with more limited resources to manage the types of stress they have in their lives, we’d get better results. “

Classical conditioning experiments link a neutral stimulus, such as a sound or a picture, to an event, like eating or smoking. Higher order, sometimes called second order conditioning, links this neutral stimulus to a second event. In the case of Pavlov’s dogs, if they could have been trained to associate a light being switched on with the sound of the bell and consequently began to salivate to the light only this would be second order conditioning.

Marianne Littel and Prof Franken, from the Erasmus University Rotterdam, compared the reactions of smokers and non-smokers to a smoking related picture or to a neutral (non-smoking related) picture. These classical responses were then paired to a second round of neutral stimuli – the researchers chose a geometric shape (a cube or a pyramid). The responses of the subjects, such as their cravings and EEG measurements of brain activity, were recorded at each stage.

For both smokers and non-smokers the EEG results showed that P3 brain waves (thought to be involved in attention) are bigger for the shape paired with smoking related stimulus (CS2s) than to the shape paired with non-smoking related cues (CS2n).

Marianne Littel explained, “All our participants had greater second order conditioning for smoking-related cues than the neutral cues, showing how smoking captures everyone’s attention. However for the smokers only this training was related to feelings of craving and pleasure.”

She continued, “Importantly, the smokers had larger P3 waves for CS2s than non-smokers, suggesting that smokers also have an enhanced ability for drug-related ‘associative learning’ compared to non-addicts. When the experiment was continued the differences between smokers/non-smokers were lost. This may indicate that second order conditioning is transient or simply that the participants lost interest and concentration.”

This hypothesis is supported by human functional brain imaging studies, which consistently report the activation of several brain regions during craving that involve regions in the cerebral cortex as well as the limbic system, a brain circuit involved in emotion.

Building on these brain imaging studies, scientists at the Center for Nicotine and Smoking Cessation Research at Duke University Medical Center manipulated this ‘craving circuit’ activity using transcranial magnetic stimulation (TMS), a non-invasive technique that uses electromagnetic currents to target specific or general areas of the brain. Depending upon the frequency used, it can either stimulate or depress brain activity.

The researchers found that the delivery of repeated TMS to the superior frontal gyrus at high frequency (10 Hz) increased craving for cigarettes.

“We directly stimulated a frontal brain region using magnetic fields and showed that it exaggerated smokers’ craving for cigarettes when they viewed smoking related cues. By gaining a better understanding of how the brain influences craving responses, strategies for blocking these responses can be devised and ultimately more effective smoking cessation treatments may be developed,” explained Dr. Jed Rose, one of the study authors.

However, they did not find that low frequency (1 Hz) stimulation reduced craving. Thus, a potential intervention that may have reduced the activation within this circuit did not produce the opposite effect.

Nonetheless, the high frequency stimulation reduced craving when participants were viewing nonsmoking cues. Moreover, the ability of smoking to satisfy craving, a rewarding effect that helps keep smokers “hooked,” was partially blocked by high frequency stimulation. These effects need to be explored for potential therapeutic applications.

“This elegant study implicates the superior frontal gyrus in controlling the activity of the craving circuit,” commented Dr. John Krystal, Editor of Biological Psychiatry. “Additional research will be needed to determine the potential value of repetitive TMS as a treatment for smoking.” 

Depression is a common disorder that negatively affects quality of life for people with the condition. About 65% of people with depression have repeat episodes. Depression can be associated with weight and dietary control, pain and inattention to other health issues.

To identify risk factors associated with a long-term prognosis of depression, researchers looked at 585 adults from Statistics Canada’s National Population Health Survey who had suffered depression in 2000/01. Of the patients, 65% were women, the average age was 38.5 years, and 82% were in the middle- to high-income bracket. More than half the patients had one or more episodes of depression in the following six years. Being an immigrant appeared to have protective status against relapse in people with severe depression.

The researchers found that age, sex and income were not associated with future depressive episodes but that daily smoking and low mastery were associated with long-term depression. Mastery is the sense that people have control over their lives and their circumstances. In this study, high levels of mastery appeared to be protective against further depression.

“History of depression is a well-known clinical indicator of future depressive episodes; however, smoking and mastery are more novel prognostic factors that are not well accounted for in current clinical practice,” states Dr. Ian Colman, Department of Epidemiology and Community Medicine, University of Ottawa, with coauthors.

“Future research should evaluate the benefits of including smoking cessation and mastery in existing clinical guidelines for the treatment of depression,” they conclude.

The researchers investigated this growing phenomenon through a survey of 104 long-term e-cigarette users. E-cigs typically consist of a cigarette-shaped device with a battery, a heating element and a cartridge containing propylene glycol and nicotine. Users puff on the mouthpiece to activate a circuit that heats the atomizer and produces a vapor. The users then inhale.

“If some smokers have difficulty overcoming both nicotine dependence and long-term habit change, then surely one solution is to help them avoid most of the health risks with only a minimal alteration in their nicotine-seeking habit,” said Jonathan Foulds, Ph.D., professor of public health sciences and psychiatry. “This implies a nicotine replacement device that looks like a cigarette and delivers nicotine like a cigarette, but does not deliver the tar and carbon monoxide that cause the vast majority of smoking-caused disease.”

The study found that 78 percent of long-term users were no longer using tobacco and planned on using their e-cig instead. Interestingly, only 8 percent were using the most widely marketed style of cigarette-shaped e-cigs. Most had learned that these do not deliver adequate nicotine and had used online forums and personal experience to find out which types of e-cigs deliver a satisfying effect capable of keeping them off real cigarettes, the researchers reported in a recent issue of the International Journal of Clinical Practice.

“These products initially seemed to be something of a gimmick and likely to be banned by the FDA,” said Foulds. “However, they are continuing to be popular and at least some smokers appear to find them helpful. However, we just don’t have enough information on their long-term safety and effectiveness for clinicians to recommend them.

“Until that research has been carried out, I would advise smokers to use proven treatments. The treatments that have been proven to work include counseling (e.g. available for free via 1-800-QUIT NOW), nicotine replacement, bupropion or varenicline.”

An additional problem with e-cigarettes, Foulds said, is that there appears to be poor quality control. Some sold as “high nicotine” appear to deliver very little nicotine, and there are concerns about the quality of the labeling and instructions.

“I am particularly concerned that a child may be poisoned by drinking the flavored liquid designed for e-cigarettes,” Foulds said. “These types of products have the potential to help smokers to quit, but right now tighter quality control and regulation is needed.”

Foulds also noted that the sample of e-cig users participating in the study were not representative of all e-cig users, but were a self-selected sub-sample of enthusiasts who have used the products, on average, for over a year.

Over the course of four weeks, mice genetically engineered to lack the gene for protein kinase C (PKC) epsilon consumed less of a nicotine-containing water solution than normal mice, and were less likely to return to a chamber in which they had been given nicotine.

In contrast, normal mice steadily increased their consumption of nicotine solution while the mice lacking PKC epsilon did not.

The study was conducted by Gallo senior associate director and investigator Robert O. Messing, MD, UCSF professor of neurology, and Gallo researcher Anna M. Lee, PhD.

In normal mice, as in humans, nicotine binds to a certain class of nicotinic receptors located on dopamine neurons, which causes dopamine to be released in the brain. Dopamine creates a feeling of enjoyment, and thus prompts a sense of reward. Lee and Messing found that mice lacking PKC epsilon are deficient in these nicotinic receptors.

The study appears in the online Early Edition of the Proceedings of the National Academy of Sciences for the week of September 12, 2011.

The finding complements earlier research in which Messing found that mice genetically engineered to lack the PKC epsilon enzyme drank less alcohol than normal mice and were disinclined to return to a chamber in which they had been given alcohol.

“This could mean that these mice might not get the same sense of reward from nicotine or alcohol,” said Messing. “The enzyme looks like it regulates the part of the reward system that involves these nicotinic receptors.” The reward system is a complex of areas in the brain that affect craving for nicotine, alcohol and other addictive substances.

The next step in the research, said Messing, would be to develop compounds that inhibit PKC epsilon. The ultimate goal, he said, would be medications that could be used “to take the edge off of addiction by helping people get over some of their reward craving.”

“The data indicate that for some young adults smoking is impulsive,” said Andrew Littlefield, a doctoral student in the Department of Psychology in the College of Arts and Science. “That means that 18-year-olds are acting without a lot of forethought and favor immediate rewards over long term negative consequences. They might say, ‘I know smoking is bad for me, but I’m going to do it anyway.’ However, we find individuals who show the most decreases in impulsivity also are more likely quit smoking. If we can target anti-smoking efforts at that impulsivity, it may help the young people stop smoking.”

In the study, MU researchers compared people, aged 18-35, who smoked with those who had quit smoking. They found that individuals who smoked were higher in two distinct personality traits during young adulthood:

• impulsivity – acting without thinking about the consequences
• neuroticism – being emotionally negative and anxious, most of the time

Littlefield found that those with higher levels of impulsivity and neuroticism were more likely to engage in detrimental behaviors, such as smoking. However, Littlefield also found that those who quit smoking had the biggest declines in impulsivity and neuroticism from ages 18 to 25.

“Smokers at age 18 had higher impulsivity rates than non-smokers at age 18, and those who quit tended to display the steepest declines in impulsivity between ages 18 and 25,” Littlefield said. “However, as a person ages and continues to smoke, smoking becomes part of a regular behavior pattern and less impulsive.  The motives for smoking later in life – habit, craving, loss of control and tolerance – are key elements of smoking dependence and appear to be more independent of personality traits.”

Littlefield says the tobacco use study will contribute to ongoing research on the relationship between personality and substance abuse. He recently received a $30,000 grant from the National Institutes of Health to study genetic influences on personality and alcohol drinking motives.

In a study recently published in the Journal of Media Psychology, Glenn Leshner, Paul Bolls and Kevin Wise, co-directors of the Psychological Research on Information and Media Effects (PRIME) Lab at the University of Missouri School of Journalism, found that showing viewers a combination of threatening and disgusting television public service announcements (PSAs) caused viewers to experience the beginnings of strong defensive reactions. The researchers found that when viewers saw the PSAs with both threatening and disgusting material, they tended to withdraw mental resources from processing the messages while simultaneously reducing the intensity of their emotional responses. Leshner says that these types of images could possibly have a “boomerang effect,” meaning the defensive reactions could be so strong that they cause viewers to stop processing the messages in the PSAs.

In their study, the researchers showed 49 participants anti-smoking television PSAs. Some PSAs included disgusting images and some did not. Further, some PSAs included an explicit health threat while others did not. The researchers monitored the participants’ emotional responses and how much attention they paid to both types of images through self-report questions as well as through sensors that measured heart rate and physiological negative emotional response from muscle activity above the eye socket on the brow.

The researchers found the PSAs which included either a threatening message or a disgusting image resulted in greater attention, better memory, and a heightened emotional response. However, PSAs that included both threatening and disgusting images caused participants to have defensive responses, where defensive reactions were so strong that the participants unconsciously limited the mental resources they allocated to processing the messages. They also had worse memories and a lower emotional responses when the threatening PSAs included disgusting images. Leshner says that when a disgusting image is included in a threatening PSA, the ad becomes too noxious for the viewer.

“We noticed in our collection of anti-tobacco public service announcements a number of ads that contained very disturbing images, such as cholesterol being squeezed from a human artery, a diseased lung, or a cancer-riddled tongue,” Leshner said. “Presumably, these messages are designed to scare people so that they don’t smoke. It appears that this strategy may backfire.”

Bolls says that the recent MU study shows that new FDA regulations requiring cigarette companies to include potentially threatening and disgusting images on cigarette packages may be ineffective at communicating the desired message that smoking is unhealthy.

“Simply trying to encourage smokers to quit by exposing them to combined threatening and disgusting visual images is not an effective way to change attitudes and behaviors,” Bolls said. “Effective communication is more complicated than simply showing a disgusting picture. That kind of communication will usually result in a defensive avoidance response where the smoker will try to avoid the disgusting images, not the cigarettes.

Bolls goes on to say that one of the major limitations of the new regulation is that the FDA is relying on smokers to take the disgusting images and make the cognitive leap that those images portray what they are doing to their bodies and that they should quit smoking to prevent those conditions.

“You can’t get that kind of message out explicitly just by putting a gross picture on a package of cigarettes; yet, that is the kind messaging that needs to take place to have a chance at changing smokers’ habits,” Bolls said. “You have to talk to smokers in a meaningful and encouraging way that outlines the consequences of smoking, but also have messages designed to minimize the defensive avoidance responses.”

Using an advanced brain imaging method, a team led by Senior Scientist Dr. Jeffrey Meyer discovered that MAO-A levels in the brain regions that control mood rose by 25 per cent eight hours after withdrawal from heavy cigarette smoking. These levels were much higher than in a comparison group of non-smoking study participants. All 48 participants filled out questionnaires, and smokers with high brain MAO-A levels during withdrawal also reported greater feelings of sadness.

“Understanding sadness during cigarette withdrawal is important because this sad mood makes it hard for people to quit, especially in the first few days. Also, heavy cigarette smoking is strongly associated with clinical depression,” said Dr. Meyer, who holds a Canada Research Chair in the Neurochemistry of Major Depression. “This is the first time MAO-A, a brain protein known to be elevated in clinical depression has been studied during cigarette withdrawal.”

MAO-A “eats up” chemicals in the brain, such as serotonin, that help maintain a normal mood. When MAO-A levels are higher as in early cigarette withdrawal, it means that this removal process is overly active, making people feel sad. For this study, MAO-A was detected using a brain imaging technique called positron emission tomography (PET). CAMH has the only PET scanner in the world dedicated solely to mental health and addiction research.

A specific substance in cigarette smoke, called harman, may be responsible for these changes, the researchers note. During active smoking, harman attaches to MAO-A. During early withdrawal in heavy smokers who had 25 or more cigarettes a day, MAO-A levels rose rapidly to a level beyond that seen in the healthy comparison group.

“This study opens new ways to prevent sad mood during cigarette withdrawal to make it easier to quit smoking. For example, it may be possible to improve the existing cigarette filters that partially screen out harman, or regulate the amount of tryptophan contained in cigarettes, since tryptophan becomes harman when it burns,” said Dr. Meyer, who is also head of the Neurochemical Imaging Program in Mood Disorders at CAMH’s Research Imaging Centre, and professor of psychiatry at the University of Toronto. “We also identified MAO-A as a target to shut down during the early critical stage of withdrawal with a short course of medication, but this requires further study.”

“This finding may explain why heavy smokers are at high risk for clinical depression,” says Dr. Anthony Phillips, Scientific Director of the Canadian Institutes of Health Research’s (CIHR’s) Institute of Neurosciences, Mental Health and Addiction, which funded this study.

The study, published online today in the journal Addiction, describes two experiments run by the authors. In the first experiment, run as a dummy health-food test, 74 daily smokers were given a placebo, but half were told they had taken a Vitamin C supplement. The smokers then took a one-hour unrelated survey during which they were allowed to smoke. Those who thought they had taken a vitamin pill smoked almost twice as much as those who knew they had taken a placebo (the control group) and reported greater feelings of invulnerability.

The second experiment was an expanded version of the first, with 80 participants taken from a larger community and half told they were taking a multivitamin pill. The one-hour survey also contained questions about attitudes to multivitamins. The smokers who thought they had taken a multivitamin once again smoked more than the control group. But this time, researchers found that among the multivitamin group, smokers with more positive attitudes toward multivitamins experienced a higher boost in perceived invulnerability and smoked even more than their less enthusiastic counterparts. In other words, the amount of extra smoking rose if the smoker expressed a conscious belief that multivitamins increased health.

Health-conscious smokers who take vitamins may thus trigger fundamental but false beliefs that they are invulnerable to the major health hazards associated with smoking, which will lead them to smoke more and increase their overall health risk. Says lead author Wen-Bin Chiou, “Smokers who take dietary supplements can fool themselves into thinking they are protected against cancer and other diseases. Reminding health conscious smokers that multivitamins don’t prevent cancer may help them control their smoking or even encourage them to stop.”