DRD2-related TaqIA polymorphism modulates motivation to smoke.

INTRODUCTION: TaqIA polymorphism, a genetic variant associated with the expression level of dopamine D2 receptors in the brain, has been linked to various aspects of smoking behavior, including smoking prevalence, affective withdrawal symptoms, and smoking cessation outcome. However, its involvement in motivation to smoke cigarettes has not been elucidated. METHODS: The present study examined the possible differences in self-reported reasons to smoke and craving for smoking in 160 smokers participating in a clinical trial. RESULTS: Individuals with at least one A1 allele of the TaqIA polymorphism were more likely to report smoking for stimulating effects and to reduce negative affect compared with those lacking an A1 allele. The association of the A1 genotype with a higher probability and stronger motive to smoker to enhance cognitive functioning was evident in female but not in male smokers. Female A1 carriers also expected a greater likelihood of smoking for pleasure than those without an A1 allele. A1 subjects reported stronger craving for cigarettes during early days and the last phase of a 6-week abstinence period. DISCUSSION: These results support the idea that dopaminergic transmission plays an important role in the neurobiological basis of reasons for smoking and that the TaqIA variant is one of the genetic factors underlying individual differences in these aspects. These findings also have implications for improving treatment strategies to help individuals quit smoking by controlling their motivation to continue cigarette consumption.

Serotonin transporter genotype and depressive symptoms moderate effects of nicotine on spatial working memory.

Smokers may use nicotine to self-medicate for situation-specific or person-specific cognitive or affective deficits. Although evidence suggests that nicotine replacement therapy (NRT), relative to placebo, enhances spatial working memory (SWM) in smoking-abstinent smokers with schizophrenia, the extent to which NRT may be helpful in attenuating abstinence-related SWM in other groups with deficits in SWM is unknown. Depressive symptoms are associated with both tobacco smoking and deficits in SWM. Previous studies have found that smoking abstinence increases depressive affect and depression-related hemispheric asymmetries in brain activation. Although the serotonin neurotransmitter system is closely associated with depression and the effects of nicotine, the authors are not aware of any studies that have evaluated the possible role of individual differences in serotonin transporter (5-HTT) genotype and depressive symptoms as moderators of the effects of NRT on SWM. Thus, the current study assessed the effects of NRT (nicotine patch) on SWM in relation to: (1) depressive traits and (2) 5-HTT genotype. Smoking-deprived habitual smokers (N = 64) completed the dot recall test of SWM during counterbalanced and double-blind nicotine and placebo testing sessions. There was a marginal overall effect of NRT on SWM. More importantly, NRT enhanced SWM in 5-HTT short allele carriers, relative to those with two long alleles, and this enhancement in short-allele carriers was greater for individuals with higher levels of depressive symptoms.

Neurotransmission-related genetic polymorphisms, negative affectivity traits, and gender predict tobacco abstinence symptoms across 44 days with and without nicotine patch.

Genetic and personality trait moderators of tobacco abstinence-symptom trajectories were assessed in a highly controlled study. Based on evidence suggesting their importance in stress reactivity and smoking, moderators studied were serotonin transporter gene (5-HTTLPR) and dopamine D2 receptor gene (DRD2) polymorphisms and personality traits related to negative affect (NA). Smokers were randomly assigned to quit smoking with nicotine or placebo patches. Financial incentives resulted in 80% verified abstinence across the 44-day study. Individuals with 1 or 2 short alleles of 5-HTTLPR (S carriers) experienced larger increases in NA symptoms than did those without a short allele. Nicotine replacement therapy (NRT) alleviated anxiety only in S carriers. NRT reduced NA to a greater extent in DRD2 A1 carriers than in A2A2 individuals during the 1st 2 weeks of treatment (when on the 21-mg patch); however, A1 carriers experienced a renewal of NA symptoms when switched to the 7-mg patch and when off the patch, while A2A2 individuals continued to benefit from NRT. The results suggest that the effects of genotype and treatment may vary across different durations of abstinence, treatment doses, and genotypes.

Effects of nicotine and depressive traits on affective priming of lateralized emotional word identification.

Based on evidence suggesting that depressive traits, emotional information processing, and the effects of nicotine may be mediated by lateralized brain mechanisms, analyses assessed the influence of depressive traits and nicotine patch on emotional priming of lateralized emotional word identification in 61 habitual smokers. Consistent with hypotheses, nicotine as compared to placebo patch enhanced right visual field (RVF) emotional word identification while decreasing performance of emotional word identification in the left visual field (LVF). Nicotine also enhanced positive affect and decreased negative affect. Consistent with the Heller model of depression, scoring high in depressive traits was associated with a general decrease in LVF emotional word identification. Additionally, this general LVF deficit was especially pronounced for positive word identification in individuals scoring high in trait depression. Positive primes facilitated positive target identification in the RVF and negative primes facilitated negative target identification in the LVF. Thus, nicotine promoted a LVF word-identification deficit similar to that observed in those with depressive traits. However, nicotine also enhanced RVF processing and reduced negative affect, whereas it enhanced positive affect.

Effects of nicotine on affect are moderated by stressor proximity and frequency, positive alternatives, and smoker status.

The Situation x Trait Adaptive Response (STAR) model hypothesizes that nicotine reduces negative and enhances positive affect to a greater degree in situations involving internally driven attention, as when stressor stimuli are distal (past or future), thereby allowing nicotine-primed biasing of attentional processing away from negative and toward positive stimuli. To test this hypothesis, the effects of nicotine were assessed in 64 smokers and 64 never-smokers, half of whom viewed emotionally negative pictures in a no-choice picture attention task that required them to focus on the picture stressors. The other half viewed the same stimuli in a two-choice picture attention task that presented stressor pictures in one visual field and simultaneously presented positive or neutral pictures in the other visual field. Participants received a nicotine patch during one session and a placebo patch during the other session. Nicotine modulated affect only in smokers. In smokers, compared with placebo, nicotine patch reduced negative affect more during the distal periods (between stressors) than during actual stressor exposure and in women reduced negative affect more when the proportion of negative stimuli was low. Nicotine also enhanced positive affect more during distal than proximal stressors. Nicotine tended to reduce eye-gaze at negative pictures, especially when the alternative picture was positive. The overall findings are consistent with the view that nicotine biases attention away from negative stimuli when equally salient positive or benign stimuli are present.

Emotional stimuli and context moderate effects of nicotine on specific but not global affects.

The authors tested the hypothesis that the effects of nicotine on affect are moderated by the presence or absence of emotionally positive and negative stimuli and by attentional choice to avoid attending to emotionally negative stimuli. Thirty-two habitual smokers were assigned to tasks allowing attentional freedom to look back and forth at 2 simultaneously presented pictures, whereas another 32 habitual smokers viewed single pictures without attentional choice. Picture contents in both tasks were 1 of 4 combinations: emotionally negative + neutral, negative + positive, positive + neutral, or neutral + neutral. Participants wore a nicotine patch on 1 day and placebo patch on another day. Nicotine reduced anxiety most when negative pictures were presented in combination with neutral pictures, but it had no effect on anxiety when negative pictures were presented in combination with positive pictures and when negative pictures were not presented. In contrast, nicotine only reduced depressive affect when the participant had attentional choice between positive and negative pictures. Nicotine also enhanced positive affect and reduced negative affect as measured by the Positive and Negative Affect Schedule, but these effects were not moderated by task manipulations. Overall, the findings support the view that nicotine's ability to reduce specific negative affects is moderated by emotional context and attentional freedom. Nicotine tended to enhance eye-gaze orientation to emotional pictures versus neutral pictures in women, but it had no significant effect on eye-gaze in men.