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1.  Associations between Smoking and Psychiatric Comorbidity in U.S. Iraq- and Afghanistan-Era Veterans 
The risk of smoking increases with specific psychiatric diagnoses (e.g. posttraumatic stress disorder [PTSD]); but the risk has also been shown to increase as a function of the number of psychiatric illnesses with which a person is diagnosed. The current study examined this association and other correlates of smoking-psychiatric comorbidity in a sample of U.S. Iraq/Afghanistan era Veterans who have served since September 11, 2001.
The sample consisted of 1691 Veterans (mean age = 37.5 years, 20.2% women, 53.2% minority). Veterans completed measures of smoking history, nicotine dependence and smoking expectancies; they also underwent a structured diagnostic interview to establish any current and/or lifetime psychiatric diagnoses.
Consistent with previous studies, the number of comorbid diagnoses was significantly associated with both heavy (>20 cigarettes/day) and light/moderate (≤ 20 cigarette/day) smoking. Moreover, among current smokers, significant correlations between self-reported dependence and number of diagnoses were observed. Examination of self-reported smoking expectancies revealed that a greater number of diagnoses was associated with greater expectancies of negative affect reduction, stimulation/state enhancement, taste/sensorimotor manipulation, social facilitation, craving/addiction, and boredom reduction.
The present findings confirm the association between the number of comorbid diagnoses reported in previous studies, and extends those findings by identifying smoking expectancies differences among smokers with comorbid diagnoses.
PMCID: PMC3775873  PMID: 23713569
2.  I Am Your Smartphone, and I Know You Are About to Smoke: The Application of Mobile Sensing and Computing Approaches to Smoking Research and Treatment 
Nicotine & Tobacco Research  2013;15(10):1651-1654.
Much is known about the immediate and predictive antecedents of smoking lapse, which include situations (e.g., presence of other smokers), activities (e.g., alcohol consumption), and contexts (e.g., outside). This commentary suggests smartphone-based systems could be used to infer these predictive antecedents in real time and provide the smoker with just-in-time intervention. The smartphone of today is equipped with an array of sensors, including GPS, cameras, light sensors, barometers, accelerometers, and so forth, that provide information regarding physical location, human movement, ambient sounds, and visual imagery. We propose that libraries of algorithms to infer these antecedents can be developed and then incorporated into diverse mobile research and personalized treatment applications. While a number of challenges to the development and implementation of such applications are recognized, our field benefits from a database of known antecedents to a problem behavior, and further research and development in this exciting area are warranted.
PMCID: PMC3768335  PMID: 23703731
3.  Smoking withdrawal is associated with increases in brain activation during decision making and reward anticipation: A preliminary study 
Psychopharmacology  2011;219(2):563-573.
Acute nicotine abstinence is associated with disruption of executive function and reward processes; however, the neurobiological basis of these effects has not been fully elucidated.
The effects of nicotine abstinence on brain function during rewardbased probabilistic decision making were preliminarily investigated by scanning adult smokers (n = 13) following 24 hours of smoking abstinence and in a smoking satiated condition. During fMRI scanning, participants completed the wheel of fortune task (Ernst et al. 2004), a decision making task with probabilistic monetary outcomes. Brain activation was modeled during selection of options, anticipation of outcomes, and outcome feedback.
During choice selection, reaction times were slower, and there was greater neural activation in the postcentral gyrus, insula, frontal and parietal cortices in the abstinent compared to satiated condition. During reward anticipation, greater activation was observed in the frontal pole, insula, and paracingulate cortex in the abstinent compared to satiated condition. Greater activation was also shown in the precentral gyrus and putamen in the satiated condition compared to the abstinent condition. During the outcome phase, rewards (compared to no rewards) resulted in significant activation in the paracingulate cortex in the satiated compared to abstinent condition.
The results of this preliminary study suggest that smoking withdrawal results in greater recruitment of insular, frontal, and parietal cortical areas during probabilistic decision making.
PMCID: PMC4140396  PMID: 21766170
Smoking; abstinence; decision-making; risk; neuroimaging; fMRI
4.  Smoking Withdrawal Symptoms Are More Severe Among Smokers With ADHD and Independent of ADHD Symptom Change: Results From a 12-Day Contingency-Managed Abstinence Trial 
Nicotine & Tobacco Research  2011;13(9):784-792.
Smokers with attention deficit hyperactivity disorder (ADHD) have greater difficulty quitting than those without ADHD, but preliminary data (McClernon, Kollins, Lutz, Fitzgerald, Murray, Redman, et al., 2008) suggest equivalent severity of withdrawal symptoms following brief abstinence. The objective of this study was to characterize the differential effects of intermediate term smoking abstinence on self-reported withdrawal and ADHD symptoms in adult smokers with and without ADHD.
Forty adult (50% female), nontreatment seeking moderate-to-heavy smokers with and without ADHD were enrolled in a 12-day quit study in which monetary incentives were provided for maintaining biologically verified abstinence. Self-reported withdrawal, mood, and ADHD symptoms were measured pre- and post-quitting.
ADHD and controls did not vary on smoking or demographic variables. Significant Group × Session interactions were observed across a broad range of withdrawal symptoms and were generally characterized by greater withdrawal severity among ADHD smokers, particularly during the first 5 days of abstinence. In addition, Group × Sex × Session interactions were observed for craving, somatic symptoms, negative affect, and habit withdrawal; these interactions were driven by greater withdrawal severity among females with ADHD. Group × Session interactions were not observed for ADHD symptom scales.
The results of this study suggest that smokers with ADHD, and ADHD females in particular, experience greater withdrawal severity during early abstinence—independent of effects on ADHD symptoms. Whereas additional research is needed to pinpoint mechanisms, our findings suggest that smoking cessation interventions targeted at smokers with ADHD should address their more severe withdrawal symptoms following quitting.
PMCID: PMC3203401  PMID: 21571687
5.  Combined Ecological Momentary Assessment and Global Positioning System Tracking to Assess Smoking Behavior: A Proof of Concept Study 
Journal of dual diagnosis  2014;10(1):19-29.
Ecological momentary assessment (EMA) methods have provided a rich assessment of the contextual factors associated with a wide range of behaviors including alcohol use, eating, physical activity, and smoking. Despite this rich database, this information has not been linked to specific locations in space. Such location information, which can now be easily acquired from global positioning system (GPS) tracking devices, could provide unique information regarding the space-time distribution of behaviors and new insights into their determinants. In a proof of concept study, we assessed the acceptability and feasibility of acquiring and combining EMA and GPS data from adult smokers with attention deficit hyperactivity disorder (ADHD).
Participants were adults with ADHD who were enrolled in a larger EMA study on smoking and psychiatric symptoms. Among those enrolled in the latter study who were approached to participate (N = 11), 10 consented, provided daily EMA entries, and carried a GPS device with them during a 7-day assessment period to assess aspects of their smoking behavior.
The majority of those eligible to participate were willing to carry a GPS device and signed the consent (10 out of 11, 91%). Of the 10 who consented, 7 participants provided EMA entries and carried the GPS device with them daily for at least 70% of the sampling period. Data are presented on the spatial distribution of smoking episodes and ADHD symptoms on a subset of the sample to demonstrate applications of GPS data.
We conclude by discussing how EMA and GPS might be used to study the ecology of smoking and make recommendations for future research and analysis.
PMCID: PMC4036229  PMID: 24883050
global positioning system; geographic information system; ecological momentary assessment; nicotine dependence; smoking; ADHD
6.  Smoking Motivation in Adults With Attention-Deficit/Hyperactivity Disorder Using the Wisconsin Inventory of Smoking Dependence Motives 
Nicotine & Tobacco Research  2013;16(1):120-125.
Smokers with attention-deficit/hyperactivity disorder (ADHD) differ from smokers without ADHD across a range of smoking outcomes (e.g., higher prevalence rates of smoking, faster progression to regular smoking, and greater difficulty quitting). Moreover, ADHD as a disorder has been characterized by deficits in fundamental motivational processes. To date, few studies have examined how motivation for smoking might differ between nicotine-dependent individuals with and without ADHD. The goal of this study was to assess whether specific smoking motivation factors differentiate smokers with and without ADHD as measured by an empirically derived self-report measure of smoking motivations.
Smokers with (n = 61) and without (n = 89) ADHD participated in a range of laboratory and clinical studies that included the Wisconsin Inventory of Smoking Dependence Motives (WISDM).
A series of one-way analysis of covariances statistically controlling for age and race indicated that smokers with ADHD scored higher on the following WISDM subscales than their non-ADHD peers: automaticity, loss of control, cognitive enhancement, cue exposure, and negative reinforcement. Smokers in the non-ADHD group yielded higher scores on the social– environmental goads WISDM subscale. No group by gender interactions emerged.
Cigarette smokers with ADHD report different motives for smoking than smokers without ADHD. Clarifying the role of these motivational factors has implications for smoking prevention and treatment.
PMCID: PMC3916731  PMID: 24078759
7.  Effects of smoking on the acoustic startle response and prepulse inhibition in smokers with and without posttraumatic stress disorder 
Psychopharmacology  2013;230(3):10.1007/s00213-013-3181-y.
Cigarette smokers smoke in part because nicotine helps regulate attention. Prepulse inhibition (PPI) of the startle reflex is a measure of early attentional gating that is reduced in abstinent smokers and in groups with attention regulation difficulties. Attention difficulties are found in people with posttraumatic stress disorder (PTSD).
The aim of this study is to assess whether smoking and abstinence differentially affect the startle response and PPI in smokers with and without PTSD.
Startle response and PPI (prepulses at 60, 120, or 240 ms) were measured in smokers with (N=39) and without (N=61) PTSD, while smoking and again while abstinent.
Participants with PTSD produced both larger magnitude and faster latency startle responses than controls. Across groups, PPI was greater when smoking than when abstinent. The PTSD and control group exhibited different patterns of PPI across prepulse intervals when smoking and when abstinent. Older age was associated with reduced PPI, but only when abstinent from smoking.
The effects of PTSD on startle magnitude and of smoking on PPI replicate earlier studies. The different pattern of PPI exhibited in PTSD and control groups across prepulse intervals, while smoking and abstinent suggests that previous research on smoking and PPI has been limited by not including longer prepulse intervals, and that nicotine may affect the time course as well as increasing the level of PPI. The reduced PPI among older participants during abstinence suggests that nicotine may play a role in maintaining attention in older smokers, which may motivate continued smoking in older individuals.
PMCID: PMC3830656  PMID: 23828156
Smoking; Abstinence; Prepulse inhibition; Attention; Acoustic startle reflex; Posttraumatic stress disorder; Aging
8.  Smoking withdrawal shifts the spatiotemporal dynamics of neurocognition 
Addiction biology  2010;15(4):480-490.
Smoking withdrawal is associated with significant deficits in the ability to initiate and maintain attention for extended periods of time (i.e. sustained attention; SA). However, the effects of smoking abstinence on the temporal dynamics of neurocognition during SA have not been evaluated.
Twenty adult smokers underwent functional magnetic resonance imaging scans following smoking as usual and after 24-hr abstinence. During scanning they completed a SA task with two levels of task difficulty, designed to measure both sustained (i.e. over the duration of the task) and transient (i.e. event-related) activation.
Smoking abstinence significantly decreased task accuracy regardless of task difficulty. Compared to the smoking as usual, abstinence resulted in decreased sustained activation in right inferior and middle frontal gyri but increased transient activation across disperse cortical areas including precuneus and right superior frontal gyrus. Greater task difficulty was associated with even greater transient activation during abstinence in mostly right hemisphere regions including right inferior frontal gyrus.
Smoking withdrawal shifts the temporal and spatial dynamics of neurocognition from sustained, right prefrontal activation reflecting proactive cognitive control (Braver et al., 2009) to more disperse and transient activation reflecting reactive control.
PMCID: PMC2996612  PMID: 21040240
attention; fMRI; mixed-design; nicotine dependence; prefrontal cortex; smoking
9.  Childhood Economic Strains in Predicting Substance Use in Emerging Adulthood: Mediation Effects of Youth Self-Control and Parenting Practices 
Journal of Pediatric Psychology  2013;38(10):1130-1143.
Objective To examine the influence of childhood economic strains on substance use in young adulthood and to assess the mediating roles of self-control as well as positive parenting during adolescence in a nationally representative longitudinal cohort. Methods The study included data from participants (n = 1,285) in the Panel Study of Income Dynamics, Child Development Supplement, and Transition to Adult. Structural equation modeling was used to evaluate the associations among risk factors during childhood and adolescence that predicted substance use in early adulthood. Results Conditions of economic strains, especially poverty, during childhood were associated with an increased likelihood of regular smoking in adulthood, which was partially mediated by poorer self-control during adolescence. Conclusions Self-control is negatively affected by economic strains and serves as a mediator between poverty and risk of regular smoking. Additional research is needed to better understand how economic strains effect the development of self-control.
PMCID: PMC3809729  PMID: 23899658
adolescents; alcohol use; drug abuse and exposure; parent stress; parenting; tobacco use
10.  Nicotinic receptor gene variants interact with attention deficient hyperactive disorder symptoms to predict smoking trajectories from early adolescence to adulthood 
Addictive behaviors  2013;38(11):10.1016/j.addbeh.2013.06.013.
To examine the association of single nucleotide polymorphisms (SNPs) of the CHRNB3 (rs13280604) and CHRNA6 (rs892413) nicotinic acetylcholine receptor (nAChR) genes and symptoms of attention deficit hyperactivity disorder (ADHD) in predicting smoking patterns from early adolescence to adulthood.
A longitudinal cohort of 1137 unrelated youths from the National Longitudinal Study of Adolescent Health provided responses to four surveys from Waves I to IV, and a genetic sample in Wave III. Growth mixture modeling was used to identify smoking patterns and to assess the effects of the two SNPs and ADHD symptoms on cigarette use over time.
There were significant main effects of ADHD symptoms and CHRNA6 variants in predicting the number of cigarettes smoked and the pattern of use over time, respectively. There were no main effects of the CHRNB3 variants. However, a significant CHRNB3 variant × ADHD symptom interaction was observed, such that individuals with elevated ADHD symptoms and a particular CHRNB3 variant were at increased risk of cigarette use over time.
These findings demonstrate that a SNP in a nicotinic receptor gene may interact with ADHD symptoms to link with increased cigarette use across adolescence and young adulthood. Unique associations between specific variants and patterns of ADHD symptoms were identified which may be useful for targeting prevention efforts to individuals at greatest risk for cigarette smoking.
PMCID: PMC3875162  PMID: 23899432
nAChR SNPs; ADHD; Smoking development
11.  Smoking withdrawal modulates right inferior frontal cortex but not pre-supplementary motor area activation during inhibitory control 
Smokers exhibit decrements in inhibitory control (IC) during withdrawal. The objective of the current study was to investigate the neural basis of these effects in critical substrates of IC—right inferior frontal cortex (rIFC) and pre-supplementary motor area (pre-SMA). Smokers were scanned following smoking as usual and after 24-hrs smoking abstinence. During scanning they completed a Go/No-Go task which required inhibiting responses to infrequent STOP trials. Event-related brain activation in response to successfully inhibited STOP trials was evaluated in two regions of interest: rIFC (10 mm sphere, x=40, y=30, z=26) and pre-SMA (10 mm sphere, x=2, y=18, z=40). Smoking abstinence robustly increased errors of commission on STOP trials (37.1% versus 24.8% in satiated condition, p<.001) while having no effects on GO trial accuracy or reaction time (RT). In rIFC, smoking abstinence was associated with significantly increased event-related BOLD signal (p=.026). Pre-SMA was unaffected by smoking condition. The results of this preliminary study suggest that successful IC during withdrawal is associated with increased processing demands on a cortical center associated with attention to inhibitory signals.
PMCID: PMC2978758  PMID: 20861830
inhibitory control; smoking; fMRI; withdrawal; inferior frontal cortex; presupplementary motor area
12.  Individual- and community-level correlates of cigarette-smoking trajectories from age 13 to 32 in a U.S. population-based sample 
Drug and alcohol dependence  2013;132(0):301-308.
Characterizing smoking behavior is important for informing etiologic models and targeting prevention efforts. This study explored the effects of both individual- and community-level variables in predicting cigarette use vs. non-use and level of use among adolescents as they transition into adulthood.
Data on 14,779 youths (53% female) were drawn from the National Longitudinal Study of Adolescent Health (Add Health); a nationally representative longitudinal cohort. A cohort sequential design allowed for examining trajectories of smoking typologies from age 13 to 32 years. Smoking trajectories were evaluated by using a zero-inflated Poisson (ZIP) latent growth analysis and latent class growth analysis modeling approach.
Significant relationships emerged between both individual- and community-level variables and smoking outcomes. Maternal and peer smoking predicted increases in smoking over development and were associated with a greater likelihood of belonging to any of the four identified smoking groups versus Non-Users. Conduct problems and depressive symptoms during adolescence were related to cigarette use versus non-use. State-level prevalence of adolescent smoking was related to greater cigarette use during adolescence.
Individual- and community-level variables that distinguish smoking patterns within the population aid in understanding cigarette use versus non-use and the quantity of cigarette use into adulthood. Our findings suggest that efforts to prevent cigarette use would benefit from attention to both parental and peer smoking and individual well-being. Future work is needed to better understand the role of variables in the context of multiple levels (individual and community-level) on smoking trajectories.
PMCID: PMC3701734  PMID: 23499056
Smoking trajectories; zero-inflated Poisson; ZIP; LCGA; National Longitudinal Study of Adolescent Health; Add Health
13.  Methylphenidate does not influence smoking-reinforced responding or attentional performance in adult smokers with and without Attention Deficit Hyperactivity Disorder (ADHD) 
Individuals with Attention Deficit Hyperactivity Disorder (ADHD) smoke cigarettes at rates higher than the general population and questions have been raised about how stimulant drugs – the frontline pharmacological treatment for ADHD – influence smoking risk and behavior in those with ADHD. In the present study adult regular smokers with (n=16) and without (n=17) ADHD participated in 3 experimental sessions in which they completed a Progressive Ratio (PR) task to measure the relative reinforcing effects of cigarette smoking and money following oral administration of placebo and 2 active doses of methylphenidate (10 mg and 40 mg). We also measured attention and inhibitory control via a Continuous Performance Test (CPT). Methylphenidate had no effect on smoking-reinforced responding, attention, or inhibitory control in either group. Attention and inhibitory control were associated with smoking-reinforced responding, but unsystematically and only in the non-ADHD group. Several design features, such as the value of the monetary response option, the PR schedule, and the potential effects of smoking on attention and inhibitory control, could have contributed to the negative findings and are discussed as such. Although inconsistent with some previous human laboratory studies of stimulant drugs and smoking, results are consistent with recent trials of stimulant drugs as adjuncts for smoking cessation in adult smokers with ADHD. In general, methylphenidate at mild and moderate doses did not influence the relative reinforcing effects of cigarette smoking in adults with and without ADHD.
PMCID: PMC4145471  PMID: 24099358
14.  Association between smoking and retrospectively reported attention-deficit/hyperactivity disorder symptoms in a large sample of new mothers 
Nicotine & Tobacco Research  2009;11(3):313-322.
This study investigated the association between retrospectively reported attention-deficit/hyperactivity disorder (ADHD) symptoms experienced during childhood and five cigarette smoking–related outcomes in adulthood.
A large sample (N = 1,117) of new mothers participating in an ongoing longitudinal study completed retrospective reports of their childhood ADHD symptomatology, as well as concurrent and retrospective reports of their smoking behavior. Linear regression models tested the association between ADHD symptomatology and smoking outcomes.
Childhood ADHD symptomatology was predictive of the number of cigarettes smoked per day currently and during pregnancy, as well as the age at onset of smoking. We found nonlinear associations between hyperactive–impulsive symptoms and the number of cigarettes smoked per day in pregnancy, as well as between inattentive symptoms and the number of cigarettes smoked per day currently. Women who retrospectively reported intermediate levels of ADHD symptoms during their childhood reported smoking more cigarettes per day than women who reported low or high levels of ADHD symptoms during childhood. We also found multiplicative relationship between inattentive and hyperactive–impulsive symptoms, such that inattentive symptoms were predictive of an earlier age at smoking onset only when hyperactive–impulsive symptoms were low; moreover, the magnitude of this association was stronger for Black relative to White women.
These findings demonstrate the importance of considering differential effects of ADHD symptoms and smoking outcomes as a function of sex and race. They also represent a potentially indirect means through which women who have even a moderate childhood history of ADHD symptomatology may create a set of circumstances that compromise the health and well-being of their own children.
PMCID: PMC2666380  PMID: 19307443
15.  Examining the effects of initial smoking abstinence on response to smoking-related stimuli and response inhibition in a human laboratory model 
Psychopharmacology  2013;231(10):2145-2158.
Research is needed on initial smoking abstinence and relapse risk.
This study aims to investigate the effects of different durations of initial abstinence on sensitivity to smoking-related stimuli and response inhibition in the context of a larger battery of outcome measures.
Smokers were randomly assigned to receive payment contingent on smoking abstinence across all 15 study days (15C) or just the final 2 days (2C). Smoking status and subject ratings were assessed daily. Participants completed fMRI sessions at baseline and day 14 during which they completed craving ratings after exposure to smoking-related and neutral stimuli and performed a response inhibition task. On day 15, participants completed a smoking preference session involving 20 exclusive choices between smoking and money.
The payment contingencies were effective in producing greater smoking abstinence in the 15C vs. 2C conditions. Ratings of withdrawal decreased, while ratings of ease and confidence in abstaining increased in the 15C vs. 2C conditions across the 15-day study. 15C participants were less likely to choose the smoking option in the preference session. 15C participants reported greater reductions in craving compared to the 2C participants in the presence of smoking-related and neutral stimuli (i.e., decreases in generalized craving), but no differences were noted in cue reactivity per se or in response inhibition.
Results systematically replicate prior observations that a period 2 weeks of initial abstinence decreases the relative reinforcing effects of smoking and improves other outcomes associated with relapse risk compared to the initial day or two of a cessation effort, and extends them by underscoring the importance of generalized rather than cue-induced craving in relation to relapse risk during the initial weeks of smoking cessation.
PMCID: PMC4123458  PMID: 24337077
Cigarette smoking; Abstinence; Reinforcement; Nicotine withdrawal; Craving; Contingency management; Financial incentives; Cue reactivity; Response inhibition
16.  24-hr smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum 
Psychopharmacology  2008;204(1):25-35.
Exposure to smoking-related cues can trigger relapse in smokers attempting to maintain abstinence.
In the present study we evaluated the effect of 24-hr smoking abstinence on brain responses to smoking-related cues using functional magnetic resonance imaging (fMRI).
Eighteen adult smokers underwent fMRI scanning following smoking as usual (satiated condition) and following 24-hr abstinence (abstinent condition). During scanning they viewed blocks of photographic smoking and control cues.
Following abstinence, greater activation was found in response to smoking cues compared to control cues in parietal (BA 7/31), frontal (BA 8/9), occipital (BA 19) and central (BA 4) cortical regions and in dorsal striatum (putamen) and thalamus. In contrast, no smoking cue > control cue activations were observed following smoking as usual. Direct comparisons between conditions (satiated vs. abstinent) showed greater brain reactivity in response to smoking cues following abstinence. In addition, positive correlations between pre-scan craving in the abstinent condition and smoking cue activation were observed in right dorsomedial prefrontal cortex (dmPFC) including superior frontal gyrus (BA 6/10), anterior cingulate gyrus (BA 32) and supplementary motor area (BA 6).
The present findings indicate smoking abstinence significantly potentiates neural responses to smoking-related cues in brain regions subserving visual sensory processing, attention and action planning. Moreover, greater abstinence-induced craving was significantly correlated with increased smoking cue activation in dmPFC areas involved in action planning and decision making. These findings suggest that drug abstinence can increase the salience of conditioned cues which is consistent with incentive-motivation models of addiction.
PMCID: PMC2810714  PMID: 19107465
cue-reactivity; craving; nicotine dependence; fMRI; smoking; dorsal striatum
17.  The association of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) with anxiety sensitivity and electronic diary negative affect among smokers with and without posttraumatic stress disorder 
Posttraumatic stress disorder (PTSD) is associated with increased smoking initiation, maintenance and relapse. Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are neurosteroids that have been associated with mood measures as well as smoking status, and nicotine is associated with increased DHEA and DHEAS levels. Given the difficulties with mood experienced by smokers with PTSD, the purpose of the current study was to evaluate the association between negative affect and anxiety sensitivity with DHEA and DHEAS levels. Ninety-six smokers with and without PTSD provided blood samples for neurosteroid analyses, and completed self-report measures of anxiety sensitivity and electronic diary ratings of negative affect. As expected, PTSD smokers reported higher levels of anxiety sensitivity (F[1,94]=20.67, partial η2= 0.18, p<.0001) and negative affect (F[1,91]=7.98, partial η2= .08, p=.006). After accounting for age and gender, DHEAS was significantly inversely associated with both anxiety sensitivity (F[3,92]=6.97, partial η2= 0.07, p=.01) and negative affect (F[3,87]=10.52, partial η2= 0.11, p=.002) across groups. Effect sizes indicated that these effects are moderate to high. No significant interactions of diagnosis and DHEA(S) levels with mood measures were detected. Given that nicotine is known to elevate DHEA(S) levels, these results suggest that DHEAS may serve as a biomarker of the association between mood and nicotine among smokers. Implications for the results include 1) the use of DHEAS measurement across time and across quit attempts; and 2) the potential for careful use of DHEA supplementation to facilitate abstinence during smoking cessation.
PMCID: PMC3896952  PMID: 23771199
18.  Neuroimaging of Nicotine Dependence: Key Findings and Application to the Study of Smoking-Mental Illness Comorbidity 
Journal of dual diagnosis  2009;5(2):168-178.
Modern neuroimaging techniques offer the opportunity to non-invasively study neuroanatomical and neurofunctional correlates of nicotine dependence and its treatment. In the present review, the most widely used neuroimaging techniques—magnetic resonance imaging (MRI), positron emission tomography (PET) and functional MRI (fMRI)—are briefly described and their strengths and limitations discussed. The use of these techniques has resulted in new insights into the neuropharmacology of tobacco addiction. Studies comparing smokers and nonsmokers have shown that smokers have less grey matter density in frontal brain regions and greater concentrations of nicotinic receptors. Research on the effects of smoking a cigarette confirms that smoking leads to the release of dopamine in brain reward areas and to nicotinic receptor binding. Studies of smoking abstinence have identified functional brain correlates of increased reactivity to smoking-related cues, and worsening of concentration. To date, neuroimaging studies of nicotine dependence among individuals with mental illness have focused almost exclusively on schizophrenia. A conceptual/methodological framework for studying dual diagnosis using neuroimaging measures is provided with the aim of spurring additional research in this area.
PMCID: PMC2743422  PMID: 19756221
MRI; fMRI; PET; nicotine; smoking; nicotine dependence; ADHD; schizophrenia; dual diagnosis; comorbidity
19.  Smoking and the bandit: A preliminary study of smoker and non-smoker differences in exploratory behavior measured with a multi-armed bandit task 
Advantageous decision-making is an adaptive trade-off between exploring alternatives and exploiting the most rewarding option. This trade-off may be related to maladaptive decision-making associated with nicotine dependence; however, explore/exploit behavior has not been previously investigated in the context of addiction. The explore/exploit trade-off is captured by the multi-armed bandit task, in which different arms of a slot machine are chosen to discover the relative payoffs. The goal of this study was to preliminarily investigate whether smokers differ from non-smokers in their degree of exploratory behavior. Smokers (n = 18) and non-smokers (n = 17) completed a six-armed bandit task as well as self-report measures of behavior and personality traits. Smokers were found to exhibit less exploratory behavior (i.e. made fewer switches between slot machine arms) than non-smokers within the first 300 trials of the bandit task. The overall proportion of exploratory choices negatively correlated with self-reported measures of delay aversion and nonplanning impulsivity. These preliminary results suggest that smokers make fewer initial exploratory choices on the bandit task. The bandit task is a promising measure that could provide valuable insights into how nicotine use and dependence is associated with explore/exploit decision-making.
PMCID: PMC4028629  PMID: 23245198
exploration; exploitation; smoking; tobacco; multi-armed bandit task
20.  Effects of smoking abstinence on smoking-reinforced responding, withdrawal, and cognition in adults with and without attention deficit hyperactivity disorder 
Psychopharmacology  2012;227(1):19-30.
Individuals with attention deficit hyperactivity disorder (ADHD) have a more difficult time quitting smoking compared to their non-ADHD peers. Little is known about the underlying behavioral mechanisms associated with this increased risk.
This study aims to assess the effects of 24-h smoking abstinence in adult smokers with and without ADHD on the following outcomes: smoking-reinforced responding, withdrawal, and cognitive function.
Thirty-three (n=16 with ADHD, 17 without ADHD) adult smokers (more than or equal to ten cigarettes/day) were enrolled. Each participant completed two experimental sessions: one following smoking as usual and one following biochemically verified 24-h smoking abstinence. Smoking-reinforced responding measured via a progressive ratio task, smoking withdrawal measured via questionnaire, and cognition measured via a continuous performance test (CPT) were assessed at each session.
Smoking abstinence robustly increased responding for cigarette puffs in both groups, and ADHD smokers responded more for puffs regardless of condition. Males in both groups worked more for cigarette puffs and made more commission errors on the CPT than females, regardless of condition. Smoking abstinence also increased ratings of withdrawal symptoms in both groups and smokers with ADHD, regardless of condition, reported greater symptoms of arousal, habit withdrawal, and somatic complaints. Across groups, smoking abstinence decreased inhibitory control and increased reaction time variability on the CPT. Abstinence-induced changes in inhibitory control and negative affect significantly predicted smoking-reinforced responding across groups.
Smokers with ADHD reported higher levels of withdrawal symptoms and worked more for cigarette puffs, regardless of condition, which could help explain higher levels of nicotine dependence and poorer cessation outcomes in this population. Abstinence-induced changes in smoking-reinforced responding are associated with changes in inhibitory control and negative affect regardless of ADHD status, a finding that may lead to novel prevention and treatment programs.
PMCID: PMC3624067  PMID: 23247366
ADHD; Nicotine; Reinforcement; Self-administration
21.  A Pilot Study of Lis-Dexamfetamine Dimesylate (LDX/SPD489) to Facilitate Smoking Cessation in Nicotine-Dependent Adults With ADHD 
Journal of attention disorders  2012;18(2):10.1177/1087054712440320.
The goal of this study was to assess the efficacy and tolerability of lis-dexamfetamine dimesylate (LDX) as an adjunct to nicotine replacement therapy in adult smokers with ADHD who were undergoing a quit attempt.
Thirty-two regular adult smokers with ADHD were randomized to receive LDX (n = 17) or placebo (n = 15) in addition to nicotine patch concurrent with a quit attempt.
There were no differences between smokers assigned to LDX versus placebo in any smoking outcomes. Participants treated with LDX demonstrated significant reductions in self-reported and clinician-rated ADHD symptoms. LDX was well tolerated in smokers attempting to quit.
In general, LDX does not facilitate smoking cessation in adults with ADHD more than does placebo, though both groups significantly reduced smoking. LDX demonstrated efficacy for reducing ADHD symptoms in adult smokers engaging in a quit attempt.
PMCID: PMC3421044  PMID: 22508760
adult ADHD; lis-dexamfetamine dimesylate; smoking
22.  Frontoparietal Attentional Network Activation Differs Between Smokers and Nonsmokers during Affective Cognition 
Psychiatry research  2012;211(1):57-63.
Smoking withdrawal-induced disruption of affect and cognition is associated with dysregulated prefrontal brain function although little is known regarding the neural foci of smoker-nonsmoker differences during affective cognition. Thus, the current study utilized fMRI to identify smoker-nonsmoker differences in affective cognition. Thirty-four healthy volunteers (17 smokers, 17 nonsmokers) underwent fMRI during an affective Stroop task (aST). The aST includes emotional cue-reactivity trials, and response selection trials that contain either neutral or negative emotional distractors. Smokers had less activation during negative cue-reactivity trials in regions subserving emotional awareness (i.e. posterior cingulate), inhibitory control (i.e. inferior frontal gyrus) and conflict resolution (i.e. anterior cingulate); whereas during response selection trials with negative emotional distractors, smokers had greater activation in a frontoparietal attentional network (i.e. middle frontal and supramarginal gyri). Exploratory analyses revealed that task accuracy was positively correlated with ACC and IFG BOLD response. These findings suggests that chronic nicotine use may reduce inhibitory control and conflict resolution of emotional distraction, and result in recruiting additional attentional resources during emotional interference on cognition.
PMCID: PMC3557750  PMID: 23154092
nicotine; affect; emotion; fMRI; cue-reactivity
23.  Assessing the Role of Attention-Deficit/Hyperactivity Disorder Symptoms in Smokers With and Without Posttraumatic Stress Disorder 
Nicotine & Tobacco Research  2011;14(8):986-992.
Smoking prevalence among individuals with posttraumatic stress disorder (PTSD) is elevated relative to non–PTSD smokers, and there is evidence to suggest that affect regulation may be a motivation for smoking among those with this disorder. Previous studies have also indicated that (a) PTSD is frequently comorbid with attention-deficit/hyperactivity disorder (ADHD), (b) individuals with ADHD smoke at significantly higher rates than the general population, (c) subclinical ADHD symptoms are a risk factor for smoking, and (d) affect regulation is a motivation for smoking in ADHD. The goal of this study was to assess the degree to which ADHD symptoms were uniquely associated with smoking-related affective functioning (SRAF) variables above and beyond the variance already explained by PTSD symptoms.
Smokers with (n = 55) and without PTSD (n = 68) completed measures assessing PTSD symptoms, ADHD symptoms, and SRAF.
The PTSD group endorsed significantly more severe levels of DSM-IV inattentive and hyperactive–impulsive ADHD symptoms. A series of hierarchical regressions among the entire sample indicated that, after accounting for PTSD symptoms, ADHD symptoms were associated with lower positive affect, higher negative affect, higher emotion dysregulation, higher anxiety sensitivity, and higher urges to smoke to increase positive affect.
Taken together, these findings suggest that ADHD symptoms may increase affective dysregulation difficulties already faced by smokers, particularly those with PTSD, which may, in turn, confer increased risk for smoking relapse in those with higher levels of symptomatology of both disorders.
PMCID: PMC3439866  PMID: 22180583
24.  Effects of Postnatal Parental Smoking on Parent and Teacher Ratings of ADHD and Oppositional Symptoms 
To assess the effects of postnatal parental smoking on subsequent parent and teacher ratings of DSM-IV attention deficit hyperactivity disorder (ADHD) symptoms and oppositional behaviors in children diagnosed with ADHD and their siblings. Children between 5 and 12 years of age with ADHD and their siblings were included. DSM-IV ADHD symptom subscales (Inattentive and hyperactive-impulsive), and oppositionality subscale scores from Conners’ Rating Scales were predicted on the basis of parental smoking status in the first 7 years after birth using Generalized Estimating Equations controlling for a range of relevant covariates. Postnatal parental smoking was associated with both parent and teacher ratings of ADHD symptoms and oppositional behavior. After controlling for a number of covariates, several of these relationships were still significant. The risk of maternal smoking for the development of ADHD symptoms does not end during pregnancy. Research on the mechanisms underlying the observed associations is needed.
PMCID: PMC3678953  PMID: 19525745
ADHD; smoking; disruptive behavior; nicotine dependence
25.  Smoking Abstinence and Depressive Symptoms Modulate the Executive Control System During Emotional Information Processing 
Addiction Biology  2011;17(3):668-679.
Smoking abstinence disrupts affective and cognitive processes. In this study, functional magnetic resonance imaging (fMRI) was used to investigate the effects of smoking abstinence on emotional information processing (EIP).
Smokers (n=17) and nonsmokers (n=18) underwent fMRI while performing an emotional distractor oddball task in which rare targets were presented following negative and neutral task-irrelevant distractors. Smokers completed two sessions: once following 24-hr abstinence and once while satiated. The abstinent versus satiated states were compared by evaluating responses to distractor images and to targets following each distractor valence within frontal executive and limbic brain regions. Regression analyses were done to investigate whether self-reported negative affect influences brain response to images and targets. Exploratory regression analyses examined relations between baseline depressive symptoms and smoking state on brain function.
Smoking state affected response to target detection in the right inferior frontal gyrus (IFG). During satiety, activation was greater in response to targets following negative versus neutral distractors; following abstinence, the reverse was observed. Withdrawal-related negative affect was associated with right insula activation to negative images. Finally, depression symptoms were associated with abstinence-induced hypoactive response to negative emotional distractors and task-relevant targets following negative distractors in frontal brain regions.
Neural processes related to novelty detection/attention in the right IFG may be disrupted by smoking abstinence and negative stimuli. Reactivity to emotional stimuli and the interfering effects on cognition are moderated by the magnitude of smoking state-dependent negative affect and baseline depressive symptoms.
PMCID: PMC3288802  PMID: 22081878
affect; cognition; depression; emotion; fMRI; smoking

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