Blunted striatal response to monetary reward anticipation during smoking abstinence predicts lapse during a contingency-managed quit attempt.

RATIONALE: Tobacco smoking is associated with dysregulated reward processing within the striatum, characterized by hypersensitivity to smoking rewards and hyposensitivity to non-smoking rewards. This bias toward smoking reward at the expense of alternative rewards is further exacerbated by deprivation from smoking, which may contribute to difficulty maintaining abstinence during a quit attempt. OBJECTIVE: We examined whether abstinence-induced changes in striatal processing of rewards predicted lapse likelihood during a quit attempt supported by contingency management (CM), in which abstinence from smoking was reinforced with money. METHODS: Thirty-six non-treatment-seeking smokers participated in two functional MRI (fMRI) sessions, one following 24-h abstinence and one following smoking as usual. During each scan, participants completed a rewarded guessing task designed to elicit striatal activation in which they could earn smoking and monetary rewards delivered after the scan. Participants then engaged in a 3-week CM-supported quit attempt. RESULTS: As previously reported, 24-h abstinence was associated with increased striatal activation in anticipation of smoking reward and decreased activation in anticipation of monetary reward. Individuals exhibiting greater decrements in right striatal activation to monetary reward during abstinence (controlling for activation during non-abstinence) were more likely to lapse during CM (p < 0.025), even when controlling for other predictors of lapse outcome (e.g., craving); no association was seen for smoking reward. CONCLUSIONS: These results are consistent with a growing number of studies indicating the specific importance of disrupted striatal processing of non-drug reward in nicotine dependence and highlight the importance of individual differences in abstinence-induced deficits in striatal function for smoking cessation.

Biomarkers for smoking cessation.

One way to enhance therapeutic development is through the identification and development of evaluative tools such as biomarkers. This review focuses on putative diagnostic, pharmacodynamic, and predictive biomarkers for smoking cessation. These types of biomarkers may be used to more accurately diagnose a disease, personalize treatment, identify novel targets for drug discovery, and enhance the efficiency of drug development. Promising biomarkers are presented across a range of approaches including metabolism, genetics, and neuroimaging. A preclinical viewpoint is also offered, as are analytical considerations and a regulatory perspective summarizing a pathway toward biomarker qualification.

Effects of unexpected changes in visual scenes on the human acoustic startle response and prepulse inhibition.

Prepulse inhibition (PPI) refers to the process wherein startle responses to salient stimuli (e.g., startling sound pulses) are attenuated by the presentation of another stimulus (e.g., a brief pre-pulse) immediately before the startling stimulus. Accordingly, deficits in PPI reflect atypical sensorimotor gating that is linked to neurobehavioral systems underlying responsivity to emotionally evocative cues. Little is known about the effects of changes in visual contextual information in PPI among humans. In this study, the effects of introducing unexpected changes in the visual scenes presented on a computer monitor on the human auditory startle response and PPI were assessed in young adults. Based on our animal data showing that unexpected transitions from a dark to a light environment reduce the startle response and PPI in rats after the illumination transition, it was hypothesized that novel changes in visual scenes would produce similar effects in humans. Results show that PPI decreased when elements were added to or removed from visual scenes, and that this effect declined after repeated presentations of the modified scene, supporting the interpretation that the PPI reduction was due to novel information being processed. These findings are the first to demonstrate that novel visual stimuli can impair sensorimotor gating of auditory stimuli in humans.

Association between attention-deficit/hyperactivity disorder symptoms and obesity and hypertension in early adulthood: a population-based study.

OBJECTIVE: To examine the associations between attention-deficit/hyperactivity disorder (ADHD) symptoms, obesity and hypertension in young adults in a large population-based cohort. DESIGN, SETTING AND PARTICIPANTS: The study population consisted of 15,197 respondents from the National Longitudinal Study of Adolescent Health, a nationally representative sample of adolescents followed from 1995 to 2009 in the United States. Multinomial logistic and logistic models examined the odds of overweight, obesity and hypertension in adulthood in relation to retrospectively reported ADHD symptoms. Latent curve modeling was used to assess the association between symptoms and naturally occurring changes in body mass index (BMI) from adolescence to adulthood. RESULTS: Linear association was identified between the number of inattentive (IN) and hyperactive/impulsive (HI) symptoms and waist circumference, BMI, diastolic blood pressure and systolic blood pressure (all P-values for trend <0.05). Controlling for demographic variables, physical activity, alcohol use, smoking and depressive symptoms, those with three or more HI or IN symptoms had the highest odds of obesity (HI 3+, odds ratio (OR)=1.50, 95% confidence interval (CI) = 1.22-2.83; IN 3+, OR = 1.21, 95% CI = 1.02-1.44) compared with those with no HI or IN symptoms. HI symptoms at the 3+ level were significantly associated with a higher OR of hypertension (HI 3+, OR = 1.24, 95% CI = 1.01-1.51; HI continuous, OR = 1.04, 95% CI = 1.00-1.09), but associations were nonsignificant when models were adjusted for BMI. Latent growth modeling results indicated that compared with those reporting no HI or IN symptoms, those reporting 3 or more symptoms had higher initial levels of BMI during adolescence. Only HI symptoms were associated with change in BMI. CONCLUSION: Self-reported ADHD symptoms were associated with adult BMI and change in BMI from adolescence to adulthood, providing further evidence of a link between ADHD symptoms and obesity.

EEG, physiology, and task-related mood fail to resolve across 31 days of smoking abstinence: relations to depressive traits, nicotine exposure, and dependence.

Changes in task-related mood and physiology associated with 31 days of smoking abstinence were assessed in smokers, 34 of whom were randomly assigned to a quit group and 22 to a continuing-to-smoke control group. A large financial incentive for smoking abstinence resulted in very low participant attrition. Individuals were tested during prequit baselines and at 3, 10, 17, and 31 days of abstinence. Abstinence was associated with decreases in heart rate and serum cortisol, a slowing of electroencephalogram (EEG) activity, and task-dependent and trait-depression-dependent hemispheric EEG asymmetries. Differences between the quit group and the smoking group showed no tendency to resolve across the 31 days of abstinence. Trait depression and neuroticism correlated with increases in left-relative-to-right frontal EEG slow-wave (low alpha) activity at both 3 and 31 days of abstinence. In contrast, prequit nicotine intake and Fagerström Tolerance scores correlated with alpha asymmetry and with greater EEG slowing only at Day 3. Thus, the effects of smoking abstinence appear to last for at least several months.

Effects of monetary contingencies on smoking relapse: influences of trait depression, personality, and habitual nicotine intake.

Of 56 male smokers, 34 were randomly assigned (by 60% random odds) to quit smoking immediately, whereas the remaining 22 were assigned to quit after an additional 31 days. Compensation ($300) was contingent on abstinence for a minimum of 31 or 2 days (depending on random assignment) and completion of all experimental sessions. Contingencies for the immediate-quit group required 31 days of abstinence; those for the delayed-quit group required only 2 days of abstinence. Contingency duration (31 vs. 2 days) predicted days to relapse. All but 4 of the 31-day contingency participants maintained abstinence for at least 31 days, whereas only 3 of the 2-day contingency group abstained for 31+ days. However, 31-day contingencies did not result in longer postcontingency time to relapse. Higher trait neuroticism, depression, and psychopathic deviate scores predicted decreased time to relapse. Prequit cotinine concentrations and Fagerström Tolerance Questionnaire scores failed to predict time to relapse.

Effects of smoking and telic/paratelic dominance on the contingent negative variation (CNV).

Concepts from reversal theory, a general theory of motivation, emotion and action, have recently been shown to be relevant to smoking behavior and smoking cessation. One relevant concept is that of telic and paratelic dominance. Individuals who are paratelic-dominant are playful, spontaneous, and prefer high arousal seeking. Those who are telic-dominant are serious, tend to plan ahead, and prefer low arousal. This led to the hypothesis that smoking might increase the amplitude of the contingent negative variation (CNV) in paratelic-dominant smokers more than in telic-dominant smokers. CNV was obtained using a Go/NoGo reaction time task with a 2 s S1-S2 interval and variable intertrial intervals. S1 indicated whether the subject was to respond to S2 or not. Errors were punished with a burst of white noise. Subjects performed the CNV task three times: after being deprived of smoking for at least 4 h; after sham smoking; and after smoking a cigarette of their own brand. Telic-dominant subjects differed from paratelic-dominant subjects in the relative amplitude of early (1 s) and late (2 s) components of the CNV. Smoking did not differentially affect the dominance groups unless gender was taken into account, and the most striking interactions between smoking and dominance groups were noted for the NoGo trials. As expected, smoking decreased the amplitude of the early component of the NoGo CNV for telic-dominant women, but increased it for paratelic-dominant women; no significant differences were found for the late component. In men, smoking increased the late CNV more for telics than for paratelics, while smoking did not differentially affect the early component.

Smoking and EEG power spectra: effects of differences in arousal seeking.

Reversal theory, a general theory of motivation, emotion and action, has recently been shown to predict lapses in smoking cessation. Individuals are less likely to lapse if they are in the telic (serious-minded, arousal avoidant, goal-oriented) state than when they are in the paratelic (playful, arousal seeking, spontaneous) state. The literature indicates that people can smoke in such a way as to either increase or decrease central nervous system arousal; smoking in the telic and paratelic states might therefore differentially affect the resting electroencephalograph, as quantified by Fast Fourier Transform analysis. The basic hypothesis was supported. Theta power was decreased when subjects in the telic state smoked, while beta 2 power was increased when subjects in the paratelic state smoked; the latter finding was, however, true only for men. The results have important implications for research on changing health behaviors and for smoking cessation programs.