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1.  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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  Alpha-2 Adrenergic Receptors and Attention—Deficit/Hyperactivity Disorder 
Current psychiatry reports  2010;12(5):366-373.
Pharmacological management of attention-deficit hyperactivity disorder (ADHD) has expanded beyond stimulant medications to include alpha 2 adrenergic agonists. These agents exert their actions through presynaptic stimulation and likely involve facilitation of both dopamine and noradrenaline neurotransmission, which are both thought to play critical roles in the pathophysiology of ADHD. Further, frontostratial dysfunction giving rise to neuropsychological weaknesses has been well-established in patients with ADHD and may explain how alpha 2 agents exert their beneficial effects. In the following review, we consider relevant neurobiological underpinnings of ADHD with respect to why alpha 2 agents may be effective in treating this condition. We also review new formulations of alpha 2 agonists, emerging data on their use in ADHD, and implications for clinical practice. Integrating knowledge of pathphysiological mechanisms and mechanisms of drug action may inform our medication choices and facilitate treatment of ADHD and related disorders.
PMCID: PMC3676929  PMID: 20652773
guanfacine; clonidine; prefrontal; noradrenaline; ADHD
9.  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
10.  Ecological Momentary Assessment of Antecedents and Consequences of Smoking in Adults with Attention-Deficit/Hyperactivity Disorder 
Substance use & misuse  2014;49(11):1446-1456.
The current study assessed antecedents and consequences of ad lib cigarette smoking in smokers diagnosed with attention-deficit/hyperactivity disorder (ADHD) using ecological momentary assessment (EMA). Adult smokers with ADHD (n = 17) completed 870 smoking and 622 nonsmoking electronic diary entries over a seven-day observation period of their naturalistic smoking behavior. Data collection occurred from 2011 to 2012. Generalized estimating equations indicated that ADHD smokers were more likely to smoke when urge to smoke, negative affect, boredom, stress, worry, and restlessness were elevated. In addition, participants were more likely to smoke in situations that elicited higher levels of nervousness and frustration. ADHD symptoms, in general, did not differ between smoking and nonsmoking contexts, though hyperactive-impulsive ADHD symptoms were elevated prior to smoking in frustrating situations. Additional situational antecedent variables were associated with smoking, including being in the presence of others smoking, being in a bar or restaurant, while outside, and while consuming caffeinated or alcoholic beverages. Participants also reported a significant improvement in urge to smoke, negative affect, stress, hunger, and ADHD symptoms after smoking a cigarette. Findings suggest certain contextual factors that may maintain ad lib cigarette smoking in smokers with ADHD and identify potential treatment targets in smoking cessation interventions for this at-risk group. Clinical implications and future research directions are discussed. Funding for this study was provided by the National Institute on Drug Abuse.
PMCID: PMC4116432  PMID: 24827866
attention-deficit/hyperactivity disorder; nicotine dependence; cigarette smoking; affect; emotion dysregulation; ecological momentary assessment
11.  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
12.  Clonidine Extended-Release Tablets as Add-on Therapy to Psychostimulants in Children and Adolescents With ADHD 
Pediatrics  2011;127(6):e1406-e1413.
To assess the efficacy and safety of clonidine hydrochloride extended-release tablets (CLON-XR) combined with stimulants (ie, methylphenidate or amphetamine) for attention-deficit/hyperactivity disorder (ADHD).
In this phase 3, double-blind, placebo-controlled trial, children and adolescents with hyperactive- or combined-subtype ADHD who had an inadequate response to their stable stimulant regimen were randomized to receive CLON-XR or placebo in combination with their baseline stimulant medication. Predefined efficacy measures evaluated change from baseline to week 5. Safety was assessed by spontaneously reported adverse events, vital signs, electrocardiogram recordings, and clinical laboratory values. Improvement from baseline for all efficacy measures was evaluated using analysis of covariance.
Of 198 patients randomized, 102 received CLON-XR plus stimulant and 96 received placebo plus stimulant. At week 5, greater improvement from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score (95% confidence interval: −7.83 to −1.13; P = .009), ADHD-RS-IV hyperactivity and inattention subscale scores (P = .014 and P = .017, respectively), Conners' Parent Rating Scale scores (P < .062), Clinical Global Impression of Severity (P = .021), Clinical Global Impression of Improvement (P = .006), and Parent Global Assessment (P = .001) was observed in the CLON-XR plus stimulant group versus the placebo plus stimulant group. Adverse events and changes in vital signs in the CLON-XR group were generally mild.
The results of this study suggest that CLON-XR in combination with stimulants is useful in reducing ADHD in children and adolescents with partial response to stimulants.
PMCID: PMC3387872  PMID: 21555501
α2-adrenergic agonist; attention-deficit/hyperactivity disorder; clonidine–hydrochloride extended-release tablets; psychostimulant
13.  Monetary Incentives Promote Smoking Abstinence in Adults With Attention Deficit Hyperactivity Disorder (ADHD) 
Individuals with attention deficit hyperactivity disorder (ADHD) smoke at rates significantly higher than the general population and have more difficulty quitting than nondiagnosed individuals. Currently, there are no evidence-based approaches for reducing smoking specifically in individuals with ADHD. Adult regular smokers with or without ADHD participated in a study of extended smoking withdrawal where monetary incentives were used to promote abstinence. Participants were paid according to an escalating schedule for maintaining abstinence measured as self-report of no smoking and an expired air carbon monoxide (CO) level of ≤4 parts per million. Sixty-four percent (14/22) of smokers with ADHD and 50% (11/22) of smokers without ADHD maintained complete abstinence for the 2-week duration of the study. Twenty-two percent (5/22) and 9% (2/22) of smokers with ADHD and without ADHD, respectively, maintained continued abstinence for up to 10 days following the removal of the contingencies. Though abstinence rates were higher for the smokers with ADHD, the group differences were not statistically significant. Results suggest that monetary incentives may be a useful approach for promoting abstinence in adult smokers with ADHD, perhaps owing to altered reinforcement processes in these individuals.
PMCID: PMC3354633  PMID: 20545386
ADHD; smoking; nicotine dependence; contingency management
14.  The Preschool Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) 6-Year Follow-up 
To describe the clinical course of attention-deficit/hyperactivity disorder (ADHD) symptom severity and diagnosis from ages 3–5 to 9–12 years during a 6-year follow-up after the original Preschool ADHD Treatment Study (PATS).
207 participants (75% male) from the original PATS, assessed at Baseline (mean age 4.4 years, when all met criteria for ADHD) and 3-months later (prior to medication treatment), were re-evaluated in three follow-up assessment visits (Year 3, mean age 7.4 years; Year 4, 8.3 years and Year 6, 10.4 years). Parents and teachers rated symptom severity and clinicians established psychiatric diagnoses. Analyses examined longitudinal changes in symptom severity and ADHD diagnosis.
Parent- and teacher-rated symptom severity decreased from Baseline to Year 3 but remained relatively stable and in the moderate-to-severe clinical range through Year 6. Girls showed generally steeper decreases in symptom T-scores. At Year 6, 89% (160/180) of remaining participants met ADHD symptom and impairment diagnostic criteria. Comorbidity of oppositional defiant disorder and/or conduct disorder was associated with a 30% higher risk of having an ADHD diagnosis at Year 6 in the multiple logistic model. Medication status during follow-up, on vs. off, did not predict symptom severity change from Year 3 to Year 6 after adjustment for other variables.
ADHD in preschoolers is a relatively stable diagnosis over a 6-year period. The course is generally chronic, with high symptom severity and impairment, in very young children with moderate-to-severe ADHD, despite treatment with medication. Development of more effective ADHD intervention strategies is needed for this age group.
PMCID: PMC3660093  PMID: 23452683
attention-deficit/hyperactivity disorder (ADHD); follow-up; pre-schoolers; development
15.  Analysis of individual items on the attention-deficit/hyperactivity disorder symptom rating scale in children and adults: the effects of age and sex in pivotal trials of lisdexamfetamine dimesylate 
Attention-deficit/hyperactivity disorder (ADHD) symptom presentation across age and sex has not been fully elucidated. The present post hoc analyses qualitatively explored the baseline levels of ADHD symptomatology across subgroups in two clinical trials of children and adults with ADHD to elucidate differences in participant presentation. The response to treatment was examined to determine patterns of response among items of the ADHD Rating Scale IV.
Exploratory post hoc analyses of ADHD Rating Scale IV item scores were conducted on data from two 4-week placebo-controlled trials in children (6–12 years) and in adults (18–55 years) with ADHD. Baseline and endpoint mean item scores were determined for subgroups defined by age (6–9, 10–12, 18–39, and 40–55 years) and sex.
The baseline mean item scores were generally numerically similar for all age-by-sex subgroups. The inattention (IA) items were numerically higher than hyperactivity/impulsivity (H/I) items among older children and adults. The endpoint mean item scores were numerically lower after lisdexamfetamine dimesylate treatment for IA and H/I items in all subgroups.
These results suggest that regardless of age or sex, baseline IA and H/I symptom profiles were comparable; however, IA vs H/I symptoms were more severe in older participants. In all age-by-sex subgroups, IA and H/I symptoms appeared to decrease after active treatment.
PMCID: PMC3862743  PMID: 24363557
ADHD symptom items
16.  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
17.  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
18.  Treatment for Co-Occurring Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder 
Neurotherapeutics  2012;9(3):518-530.
Interest in the co-occurrence of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) has grown in the last decade. Research on clinical populations supports the frequent co-occurrence of ADHD traits (e.g., hyperactivity) in individuals with ASD and ASD traits (e.g., social communication deficits) in individuals with ADHD. Similar trends in co-occurring traits have been observed in population-based samples, as well as family and genetic studies of affected individuals. Despite increased interest in co-occurring ADHD and ASD, relatively little research has been devoted to treatment considerations. The vast majority of intervention research has examined pharmacological treatment using traditional ADHD medications. Relatively few psychosocial interventions have directly addressed co-occurring symptoms. Treatment development will benefit from enhanced understanding of the phenomenon of co-occurring ADHD and ASD. Key topics for future research include examining developmental trajectories of co-occurring disorders, comorbid psychiatric conditions, deficits in social skills, and the nature of executive functioning impairment in individuals with co-occurring ADHD and ASD. In the current review, research in these areas is reviewed along with recommendation for future study. Given that clinicians are routinely observing and treating individuals with co-occurring symptoms, further research will yield needed information to inform intervention development and maximize benefits for affected individuals.
Electronic supplementary material
The online version of this article (doi:10.1007/s13311-012-0126-9) contains supplementary material, which is available to authorized users.
PMCID: PMC3441928  PMID: 22678458
ADHD; autism spectrum disorder; psychopharmacology; psychosocial treatment
19.  Long-Term Stimulant Treatment Affects Brain Dopamine Transporter Level in Patients with Attention Deficit Hyperactive Disorder 
PLoS ONE  2013;8(5):e63023.
Brain dopamine dysfunction in attention deficit/hyperactivity disorder (ADHD) could explain why stimulant medications, which increase dopamine signaling, are therapeutically beneficial. However while the acute increases in dopamine induced by stimulant medications have been associated with symptom improvement in ADHD the chronic effects have not been investigated.
We used positron emission tomography and [11C]cocaine (dopamine transporter radioligand) to measure dopamine transporter availability in the brains of 18 never-medicated adult ADHD subjects prior to and after 12 months of treatment with methylphenidate and in 11 controls who were also scanned twice at 12 months interval but without stimulant medication. Dopamine transporter availability was quantified as non-displaceable binding potential using a kinetic model for reversible ligands.
Twelve months of methylphenidate treatment increased striatal dopamine transporter availability in ADHD (caudate, putamen and ventral striatum: +24%, p<0.01); whereas there were no changes in control subjects retested at 12-month interval. Comparisons between controls and ADHD participants revealed no significant difference in dopamine transporter availability prior to treatment but showed higher dopamine transporter availability in ADHD participants than control after long-term treatment (caudate: p<0.007; putamen: p<0.005).
Upregulation of dopamine transporter availability during long-term treatment with methylphenidate may decrease treatment efficacy and exacerbate symptoms while not under the effects of the medication. Our findings also suggest that the discrepancies in the literature regarding dopamine transporter availability in ADHD participants (some studies reporting increases, other no changes and other decreases) may reflect, in part, differences in treatment histories.
PMCID: PMC3655054  PMID: 23696790
20.  Sex, ADHD symptoms, and smoking outcomes: An integrative model 
Medical Hypotheses  2012;78(5):585-593.
Both females and individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) have been found to be at increased risk for a range of smoking outcomes, and recent empirical findings have suggested that women with ADHD may be particularly vulnerable to nicotine dependence. On a neurobiological level, the dopamine reward processing system may be implicated in the potentially unique interaction of nicotine with sex and with ADHD status. Specifically, nicotine appears to mitigate core ADHD symptoms through interaction with the dopamine reward processing system, and ovarian hormones have been found to interact with nicotine within the dopamine reward processing system to affect neurotransmitter release and functioning.
This article synthesizes data from research examining smoking in women and in individuals with ADHD to build an integrative model through which unique risk for cigarette smoking in women with ADHD can be systematically explored. Based upon this model, the following hypotheses are proposed at the intersection of each of the three variables of sex, ADHD, and smoking: 1) Individuals with ADHD have altered functioning of the dopamine reward system, which diminishes their ability to efficiently form conditioned associations based on environmental contingencies; these deficits are partially ameliorated by nicotine; 2) Nicotine interacts with estrogen and the dopamine reward system to increase the positive and negative reinforcement value of smoking in female smokers; 3) In adult females with ADHD, ovarian hormones interact with the dopamine reward system to exacerbate ADHD-related deficits in the capacity to form conditioned associations; and 4) During different phases of the menstrual cycle, nicotine and ovarian hormones may interact differentially with the dopamine reward processing system to affect the type and value of reinforcement smoking provides for women with ADHD.
Understanding the bio-behavioral mechanisms underlying cigarette addiction in specific populations will be critical to developing effectively tailored smoking prevention and cessation programs for these groups. Overall, the goal of this paper is to examine the interaction of sex, smoking, and ADHD status within the context of the dopamine reward processing system not only to elucidate potential mechanisms specific to female smokers with ADHD, but also to stimulate consideration of how the examination of such individual differences can inform our understanding of smoking more broadly.
PMCID: PMC3321070  PMID: 22341778
21.  A Preliminary Analysis of Interactions Between Genotype, Retrospective ADHD Symptoms, and Initial Reactions to Smoking in a Sample of Young Adults 
Nicotine & Tobacco Research  2011;14(2):229-233.
Initial reactions to cigarettes predict later regular smoking. Symptoms of attention deficit hyperactivity disorder (ADHD) have also been shown to increase smoking risk and may moderate the relationship between genotype and smoking. We conducted an exploratory study to assess whether ADHD symptoms interact with genetic variation to predict self-reported initial reactions to smoking.
Participants were a subsample of 1,900 unrelated individuals with genotype data drawn from the National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents followed from 1995 to 2002. Linear regression was used to examine relationships among self-reported ADHD symptoms, genotype, and self-reported initial reactions to cigarettes (index scores reflecting pleasant and unpleasant reactions).
Polymorphisms in the DRD2 gene, SLC6A4 gene, and among males, the MAOA gene interacted with retrospective reports of ADHD symptoms in predicting pleasant initial reaction to cigarettes. Polymorphisms in the CYP2A6 gene and, among females, the MAOA gene interacted with retrospective reports of ADHD symptoms in predicting unpleasant initial reaction to cigarettes. No main effect for any of these polymorphisms was observed nor were any interactions with DRD4 and DAT genes.
These findings suggest that genotypes associated with monoamine neurotransmission interact with ADHD symptoms to influence initial reactions to cigarette smoking. Given that an initial pleasant reaction to cigarettes increases risk for lifetime smoking, these results add to a growing body of literature that suggests that ADHD symptoms increase risk for smoking and should be accounted for in genetic studies of smoking.
PMCID: PMC3265740  PMID: 21778150
22.  Reliability and Validity of Self- and Other-Ratings of Symptoms of ADHD in Adults 
Journal of attention disorders  2010;15(3):224-234.
Few studies have examined concordance between raters of ADHD symptoms in adults; there is less information on how well rating scales function in distinguishing adult ADHD from other disorders. This study examined these variables using the Conners Adult ADHD Rating Scales (CAARS).
The sample included 349 adults evaluated for attention problems. Correlations and kappa values were calculated using self- and observer-ratings of item-level symptoms; sensitivity, specificity, and discriminant validity of cluster scores in predicting clinician diagnoses were computed for 269 participants.
Item-level concordance rates ranged from slight to fair. Cluster scores demonstrated a poor balance of sensitivity and specificity in predicting ADHD diagnosis; a high percentage of participants with internalizing disorders had scores in the clinical range.
Self- and observer- ratings on the CAARS provide clinically relevant data about attention problems in adults, but the instrument does not effectively distinguish between ADHD and other adult psychiatric disorders.
PMCID: PMC3556723  PMID: 20424007
Adult ADHD; reliability; rating scales; sensitivity; specificity
23.  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
24.  Association between Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms and obesity and hypertension in early adulthood: A population-based study 
To examine 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 – 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.
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 ps for trend < .05). Controlling for demographic variables, physical activity, alcohol use, smoking, and depressive symptoms, those with 3 or more HI or IN symptoms had the highest odds of obesity (HI 3+ OR, 1.50; 95% CI, 1.22-2.83; IN 3+ OR, 1.21; 95% CI, 1.02-1.44) compared to 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 non-significant when models were adjusted for BMI. Latent growth modeling results indicated that compared to those reporting no HI or IN symptoms, those reporting more 3 or symptoms had higher initial levels of BMI during adolescence. Only HI symptoms were associated with change in BMI.
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.
PMCID: PMC3391591  PMID: 20975727
attention-deficit/hyperactivity disorder; obesity; hypertension; young adult; risk factors
25.  Efficacy of Guanfacine Extended Release in the Treatment of Combined and Inattentive Only Subtypes of Attention-Deficit/Hyperactivity Disorder 
Extended-release guanfacine (GXR) is approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6–17 years. This post-hoc analysis further examines the effects of GXR on hyperactivity-impulsivity and inattentiveness.
Data from two large double-blind placebo-controlled pivotal trials of GXR in the treatment of ADHD were analyzed. Using the pooled population to provide sufficient sample size and associated statistical power, the impact of GXR treatment on core ADHD symptoms was examined by comparing ADHD Rating Scale IV (ADHD-RS-IV) total scores in the overall GXR and placebo groups in subjects with each of the three ADHD subtypes. ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores in the overall study population by randomized dose group (vs. placebo) were also examined.
The full analysis set included 631 subjects aged 6–17 years (GXR: n=490; placebo: n=141). Among subjects with the predominantly inattentive subtype of ADHD, differences in least squares (LS) mean reductions from baseline in ADHD-RS-IV total scores were significantly greater in GXR-treated subjects (n=127) than in placebo-treated subjects (n=38) at treatment weeks 3 through 5 and end point (p≤0.020). Among subjects with combined type ADHD, differences in LS mean ADHD-RS-IV total score reductions from baseline were significantly greater in the GXR group (n=354) than in the placebo group (n=100) at treatment weeks 1 through 5 and end point (p≤0.011). The dearth of predominantly hyperactive-impulsive type subjects (n=12) precluded analysis of this subgroup. Each randomized GXR dose group in each trial demonstrated significantly greater reductions from baseline in ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores than did the respective placebo group at end point (p≤0.05 for all).
The results support the use of GXR in the treatment of core ADHD symptoms as defined in the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision, including hyperactivity, impulsivity, and inattention.
PMCID: PMC3373219  PMID: 22612526

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