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1.  Initial Evidence that Oprm1 Genotype Moderates Ventral and Dorsal Striatum Functional Connectivity During Alcohol Cues 
Endogenous opioids and striatal dopamine have been implicated in cue-induced alcohol craving and have been hypothesized to play a role in goal-directed, as opposed to habitual, alcohol use. This initial study examines dorsal and ventral-striatal functional connectivity during alcohol cue processing as a function of the A118G single nucleotide polymorphism (SNP) of the mu opioid receptor (OPRM1) gene.
Seventeen individuals with alcohol dependence (6 females; 90% Caucasian; mean age = 29.4) underwent blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) while performing an alcohol taste-cues task. Psychophysiological interaction (PPI) analyses investigated associations of the OPRM1 genotype with ventral and dorsal striatum functional connectivity, using the ventral striatum and the caudate as the seed region, respectively.
Compared to A-allele homozygotes, G-allele carriers of the OPRM1 gene showed (a) greater activation of the insula and orbitofrontal cortex and (b) stronger negative fronto-striatal functional connectivity for both ventral and dorsal striatal seed regions during processing of alcohol versus water cues.
These preliminary findings suggest that, relative to A-allele homozygotes, G-allele carriers show unstable frontal regulation over reward and/or habit-driven inputs from the striatum resulting from greater reward sensitivity combined with limited self-control resources.
PMCID: PMC3808494  PMID: 23876228
OPRM1; fMRI; cue-reactivity; functional connectivity; dorsal striatum; ventral striatum
2.  Impulsivity and Alcohol Demand in relation to Combined Alcohol and Caffeine Use 
Problematic alcohol use among college students continues to be a prominent concern in the United States, including the growing trend of consuming caffeine with alcoholic beverages (CABs). Epidemiologically, CAB use is associated with incremental risks from drinking, although these relationships could be due to common predisposing factors rather than specifically due to CABs. This study investigated the relationship between CAB use, alcohol misuse, and person-level characteristics including impulsive personality traits, delayed reward discounting, and behavioral economic demand for alcohol use. Participants were 273 regularly drinking undergraduate students. Frequency of CAB use was assessed over the past month. A multidimensional assessment of impulsivity included the UPPS-P questionnaire and a validated, questionnaire-based measure of delayed reward discounting. Demand was assessed via a hypothetical alcohol purchase task. Frequency of CAB consumption was significantly higher in males compared to females and was also associated with higher impulsivity on the majority of the UPPS-P subscales, steeper delayed reward discounting, and greater demand for alcohol. Significant correlations between CAB use and both alcohol demand and lack of premeditation remained present after including level of alcohol misuse in partial correlations. In a hierarchical linear regression incorporating demographic, demand, and impulsivity variables, CAB frequency continued to be a significant predictor of hazardous alcohol use. These results suggest that although there are significant associations between CAB consumption and gender, impulsivity, and alcohol demand, CAB use continues to be associated with alcohol misuse after controlling for these variables.
PMCID: PMC4118302  PMID: 24364537
Alcohol; Caffeine; Impulsivity; Demand; Delayed reward discounting
3.  Genetic basis of delay discounting in frequent gamblers: examination of a priori candidates and exploration of a panel of dopamine-related loci 
Brain and Behavior  2014;4(6):812-821.
Delay discounting is a behavioral economic index of impulsivity that reflects preferences for small immediate rewards relative to larger delayed rewards. It has been consistently linked to pathological gambling and other forms of addictive behavior, and has been proposed to be a behavioral characteristic that may link genetic variation and risk of developing addictive disorders (i.e., an endophenotype). Studies to date have revealed significant associations with polymorphisms associated with dopamine neurotransmission. The current study examined associations between delay discounting and both previously linked variants and a novel panel of dopamine-related variants in a sample of frequent gamblers.
Participants were 175 weekly gamblers of European ancestry who completed the Monetary Choice Questionnaire to assess delay discounting preferences and provided a DNA via saliva.
In a priori tests, two loci previously associated with delayed reward discounting (rs1800497 and rs4680) were not replicated, however, the long form of DRD4 VNTR was significantly associated with lower discounting of delayed rewards. Exploratory analysis of the dopamine-related panel revealed 11 additional significant associations in genes associated with dopamine synthesis, breakdown, reuptake, and receptor function (DRD3, SLC6A3, DDC, DBH, and SLC18A2). An aggregate genetic risk score from the nominally significant loci accounted for 17% of the variance in discounting. Mediational analyses largely supported the presence of indirect effects between the associated loci, delay discounting, and pathological gambling severity.
These findings do not replicate previously reported associations but identify several novel candidates and provide preliminary support for a systems biology approach to understand the genetic basis of delay discounting.
PMCID: PMC4212112  PMID: 25365808
Delay discounting; dopamine; endophenotype; genetics; impulsivity; pathological gambling
4.  Genetic basis of delay discounting in frequent gamblers: examination of a priori candidates and exploration of a panel of dopamine‐related loci 
Brain and Behavior  2014;10.1002/brb3.284.
Delay discounting is a behavioral economic index of impulsivity that reflects preferences for small immediate rewards relative to larger delayed rewards. It has been consistently linked to pathological gambling and other forms of addictive behavior, and has been proposed to be a behavioral characteristic that may link genetic variation and risk of developing addictive disorders (i.e., an endophenotype). Studies to date have revealed significant associations with polymorphisms associated with dopamine neurotransmission. The current study examined associations between delay discounting and both previously linked variants and a novel panel of dopamine‐related variants in a sample of frequent gamblers.
Participants were 175 weekly gamblers of European ancestry who completed the Monetary Choice Questionnaire to assess delay discounting preferences and provided a DNA via saliva.
In a priori tests, two loci previously associated with delayed reward discounting (rs1800497 and rs4680) were not replicated, however, the long form of DRD4 VNTR was significantly associated with lower discounting of delayed rewards. Exploratory analysis of the dopamine‐related panel revealed 11 additional significant associations in genes associated with dopamine synthesis, breakdown, reuptake, and receptor function (DRD3, SLC6A3, DDC, DBH, and SLC18A2). An aggregate genetic risk score from the nominally significant loci accounted for 17% of the variance in discounting. Mediational analyses largely supported the presence of indirect effects between the associated loci, delay discounting, and pathological gambling severity.
These findings do not replicate previously reported associations but identify several novel candidates and provide preliminary support for a systems biology approach to understand the genetic basis of delay discounting.
PMCID: PMC4212112  PMID: 25365808
Delay discounting; dopamine; endophenotype; genetics; impulsivity; pathological gambling
5.  Human Laboratory Paradigms in Alcohol Research 
Human laboratory studies have a long and rich history in the field of alcoholism. Human laboratory studies have allowed for advances in alcohol research in a variety of ways, including elucidating of the neurobehavioral mechanisms of risk, identifying phenotypically distinct sub-types of alcohol users, investigating of candidate genes underlying experimental phenotypes for alcoholism, and testing mechanisms of action of alcoholism pharmacotherapies on clinically-relevant translational phenotypes, such as persons exhibiting positive-like alcohol effects or alcohol craving. Importantly, the field of human laboratory studies in addiction has progressed rapidly over the past decade and has built upon earlier findings of alcohol's neuropharmacological effects to advancing translational research on alcoholism etiology and treatment. To that end, the new generation of human laboratory studies has focused on applying new methodologies, further refining alcoholism phenotypes, and translating these findings to studies of alcoholism genetics, medication development, and pharmacogenetics. The combination of experimental laboratory approaches with recent developments in neuroscience and pharmacology has been particularly fruitful in furthering our understanding of the impact of individual differences in alcoholism risk and in treatment response. This review of the literature focuses on human laboratory studies of subjective intoxication, alcohol craving, anxiety, and behavioral economics. Each section discusses opportunities for phenotype refinement under laboratory conditions, as well as its application to translational science of alcoholism. A summary and recommendations for future research are also provided.
PMCID: PMC4167612  PMID: 22309888
human laboratory; alcohol phenotypes; alcohol and stress; alcohol craving; impulsivity
6.  Delayed Reward Discounting and Alcohol Misuse: The Roles of Response Consistency and Reward Magnitude 
Delayed reward discounting (DRD) is a common index of impulsivity that refers to an individual’s devaluation of rewards based on delay of receipt and has been linked to alcohol misuse and other maladaptive behaviors. The current study investigated response consistency and reward magnitude effects in two measures of DRD in a sample of 111 undergraduates who consumed an average of 10.7 drinks/week. These variables were also examined in relation to alcohol use and misuse. Results indicated highly consistent performance on both measures of DRD, although significant differences were evident based on task parameters. There was also clear evidence of a magnitude effect on DRD. Finally, a number of significant associations between DRD and both alcohol use and misuse were found. These findings suggest that individuals possess a relatively consistent cognitive template for DRD choice preferences, but that the template systematically varies by both reward magnitude and delay length.
PMCID: PMC4151982  PMID: 25191534
Behavioral Economics; Delay Discounting; Alcohol; Response Consistency; Magnitude Effects
7.  Behavioral Economic Analysis of Cue-Elicited Craving for Tobacco: A Virtual Reality Study 
Nicotine & Tobacco Research  2013;15(8):1409-1416.
Subjective craving is a prominent construct in the study of tobacco motivation; yet, the precise measurement of tobacco craving poses several difficulties. A behavioral economic approach to understanding drug motivation imports concepts and methods from economics to improve the assessment of craving.
Using an immersive virtual reality (VR) cue reactivity paradigm, this study tested the hypothesis that, compared with neutral cues, tobacco cues would result in significant increases in subjective craving and diverse aspects of demand for tobacco in a community sample of 47 regular smokers. In addition, the study examined these motivational indices in relation to a dual-component delay and cigarette consumption self-administration paradigm.
In response to the VR tobacco cues, significant increases were observed for tobacco craving and the demand indices of Omax (i.e., maximum total expenditure toward cigarettes) and Breakpoint (i.e., price at which consumption is completely suppressed), whereas a significant decrease was observed for Elasticity (i.e., lower cigarette price sensitivity). Continuous analyses revealed trend-level inverse associations between Omax and Intensity in relation to delay duration and significant positive associations between subjective craving, Omax, and Elasticity in relation to the number of cigarettes purchased.
The results from this study provide further evidence for the utility of behavioral economic concepts and methods in understanding smoking motivation. These data also reveal the incremental contribution of behavioral economic indices beyond subjective craving in predicting in vivo cigarette consumption. Relationships to previous studies and methodological considerations are discussed.
PMCID: PMC3715390  PMID: 23322768
8.  Initial Development of a Measure of Expectancies for Combinations of Alcohol and Caffeine: The Caffeine+Alcohol Combined Effects Questionnaire (CACEQ) 
Caffeinated alcoholic beverage (CAB) consumption is widespread among young adults in the United States and is associated with increased negative consequences from alcohol. In addition to the direct pharmacological effects of adding caffeine to alcohol, another possible risk mechanism is via socially-learned expectancies, which has received very little consideration. The current study conducted an initial psychometric validation of a measure of CAB expectancies to facilitate research in this area. Participants were 409 undergraduate regular drinkers (71% female) who were assessed for alcohol and CAB use, alcohol use/misuse, and expectancies about CABs. The majority (62%) of participants reported CAB experience and 48% reported CAB use in the past month. Participants primarily consumed spontaneously prepared as opposed to pre-mixed CABs. More frequent CAB use was significantly positively correlated with levels of alcohol use and misuse. For the expectancy items, exploratory factor analysis revealed two factors that were labeled “Intoxication Enhancement” and “Avoid Negative Consequences.” The patterns of expectancies reflected beliefs that CABs enhanced intoxication, but did not protect against negative consequences. The measure was titled the Caffeine+Alcohol Combined Effects Questionnaire (CACEQ). Intoxication enhancement scores were significantly associated with frequency of CAB use, even after adjusting for the role of weekly drinking and alcohol misuse, supporting the convergent validity of the CACEQ. These data provide initial support for the CACEQ and suggest it may be useful for clarifying the role of expectancies in CAB use. Applications for studying the risks associated with CAB use and methodological considerations are discussed.
PMCID: PMC4118292  PMID: 23230858
Alcohol; Caffeine; Caffeinated Alcoholic Beverages; Expectancies; College Drinking
9.  Examination of the Section III DSM-5 diagnostic system for personality disorders in an outpatient clinical sample 
Journal of abnormal psychology  2013;122(4):1057-1069.
The DSM-5 includes a novel approach to the diagnosis of personality disorders (PDs) in Section III, in order to stimulate further research with the possibility that this proposal will be included more formally in future DSM iterations. The current study provides the first test of this proposal in a clinical sample by simultaneously examining its two primary components: a system for rating personality impairment and a newly developed dimensional model of pathological personality traits. Participants were community adults currently receiving outpatient mental health treatment who completed a semi-structured interview for DSM-IV PDs and were then rated in terms of personality impairment and pathological traits. Data on the pathological traits were also collected via self-reports using the Personality Inventory for DSM-5 (PID-5). Both sets of trait scores were compared to self-report measures of general personality traits, internalizing symptoms, and externalizing behaviors. Inter-rater reliabilities for the clinicians’ ratings of impairment and the pathological traits were fair. The impairment ratings manifested substantial correlations with symptoms of depression and anxiety, DSM-5 PDs, and DSM-5 pathological traits. The clinician and self-reported personality trait scores demonstrated good convergence with one another, both accounted for substantial variance in DSM-IV PD constructs, and both manifested expected relations with the external criteria. The traits but not the impairment ratings demonstrated incremental validity in the prediction of the DSM-IV PDs. Overall, the current results support the general validity of several of the components of this new PD diagnostic system and point to areas that may require further modification.
PMCID: PMC4105005  PMID: 24364607
personality disorders; DSM-5; pathological personality traits
10.  Craving as an Alcohol Use Disorder Symptom in DSM-5: An Empirical Examination in a Treatment-seeking Sample 
Craving has been added as an Alcohol Use Disorder (AUD) symptom in DSM-5 but relatively few nosological studies have directly examined the empirical basis for doing so. The current study investigated the validity of craving as an AUD symptom in a sample of heavy drinking treatment-seeking individuals. Using a semi-structured clinical interview, treatment-seeking heavy drinkers (N = 104; 62% male) were assessed for symptoms of DSM-IV AUD. The extent to which individuals endorsed pathological levels of craving in comparison to other AUD symptoms was investigated as was the association between craving and several aspects of problematic alcohol involvement. Factor analysis was utilized to examine whether craving and other AUD symptoms comprised a unidimensional syndrome. Results indicated that craving was significantly positively correlated with AUD severity, quantitative indices of drinking, and adverse consequences of alcohol abuse. In terms of frequency of endorsement, craving was present in 47% of the sample and was the 8th most frequent of the twelve symptoms evaluated. When considered with the DSM-IV AUD criteria, craving aggregated with other symptoms to form a unidimensional syndrome. Extending previous findings from epidemiological samples, these data suggest that, in a clinical sample, many relevant aspects of craving aggregate to form a diagnostic criterion that functions similarly to other AUD symptoms and is related to diverse aspects of alcohol-related impairment.
PMCID: PMC4105007  PMID: 24490710
Alcohol; Addiction; Craving; Diagnosis; Nosology
11.  Dissociable Brain Signatures of Choice Conflict and Immediate Reward Preferences in Alcohol Use Disorders 
Addiction biology  2012;10.1111/adb.12017.
Impulsive delayed reward discounting (DRD) is an important behavioral process in alcohol use disorders (AUDs), reflecting incapacity to delay gratification. Recent work in neuroeconomics has begun to unravel the neural mechanisms supporting DRD, but applications of neuroeconomics in relation to AUDs have been limited. This study examined the neural mechanisms of DRD preferences in AUDs, with emphasis on dissociating activation patterns based on DRD choice type and level of cognitive conflict. Heavy drinking adult males with (n = 13) and without (n = 12) a diagnosis of an AUD completed a monetary DRD task during a functional magnetic resonance imaging scan. Participant responses were coded based on choice type (impulsive vs. restrained) and level of cognitive conflict (easy vs. hard). AUD+ participants exhibited significantly more impulsive DRD decision-making. Significant activation during DRD was found in several decision-making regions, including dorsolateral prefrontal cortex (DLPFC), insula, posterior parietal cortex (PPC), and posterior cingulate. An axis of cognitive conflict was also observed, with hard choices associated with anterior cingulate cortex and easy choices associated with activation in supplementary motor area. AUD+ individuals exhibited significant hyperactivity in regions associated with cognitive control (DLPFC) and prospective thought (PPC) and exhibited less task-related deactivation of areas associated with the brain's default network during DRD decisions. This study provides further clarification of the brain systems supporting DRD in general and in relation to AUDs.
PMCID: PMC3871988  PMID: 23231650
Alcohol use disorders; delay discounting; neuroeconomics
12.  Biphasic Effects of Alcohol on Delay and Probability Discounting 
Delay discounting and probability discounting are behavioral economic indices of impulsive and risky decision making that have been associated with addictive behavior, but the acute biphasic effects of alcohol on these decision-making processes are not well understood. This study sought to investigate the biphasic effects of alcohol on delay and probability discounting across the ascending and descending limbs of the breath alcohol concentration (BAC) curve, which are respectively characterized by the stimulant and sedative effects of alcohol. Delay and probability discounting were measured at four time points (Baseline, Ascending, Descending, and Endpoint) across the BAC curve at two target alcohol doses (40 mg/dl and 80 mg/dl) in healthy adults (N = 23 and 27, for both doses, respectively). There was no significant effect of alcohol on delay discounting at either dose. Alcohol significantly affected probability discounting, such that reduced discounting for uncertain rewards was evident during the descending limb of the BAC curve at the lower dose (p<.05) and during both the ascending and descending limb of the BAC curve at the higher dose (p<.05). Thus, alcohol resulted in increased risky decision making, particularly during the descending limb which is primarily characterized by the sedative effects of alcohol. These findings suggest that the biphasic effects of alcohol across the ascending and descending limbs of the BAC have differential effects on behavior related to decision-making for probabilistic, but not delayed, rewards. Parallels to and distinctions from previous findings are discussed.
PMCID: PMC4050433  PMID: 23750692
delay discounting; probability discounting; impulsivity; alcohol use; behavioral economics
13.  Personality correlates of pathological gambling derived from Big Three and Big Five personality models 
Psychiatry research  2012;206(1):50-55.
Personality traits have proven to be consistent and important factors in a variety of externalizing behaviors including addiction, aggression, and antisocial behavior. Given the comorbidity of these behaviors with pathological gambling (PG), it is important to test the degree to which PG shares these trait correlates. In a large community sample of regular gamblers (N=354; 111 with diagnoses of pathological gambling), the relations between measures of two major models of personality – Big Three and Big Five – were examined in relation to PG symptoms derived from a semi-structured diagnostic interview. Across measures, traits related to the experience of strong negative emotions were the most consistent correlates of PG, regardless of whether they were analyzed using bivariate or multivariate analyses. In several instances, however, the relations between personality and PG were moderated by demographic variable such as gender, race, and age. It will be important for future empirical work of this nature to pay closer attention to potentially important moderators of these relations.
PMCID: PMC3635075  PMID: 23078872
Five-factor model; DSM-5; Statistical moderation
14.  Egocentric Social Network Analysis of Pathological Gambling 
Addiction (Abingdon, England)  2012;108(3):584-591.
To apply social network analysis (SNA) to investigate whether frequency and severity of gambling problems were associated with different network characteristics among friends, family, and co-workers. is an innovative way to look at relationships among individuals; the current study was the first to our knowledge to apply SNA to gambling behaviors.
Egocentric social network analysis was used to formally characterize the relationships between social network characteristics and gambling pathology.
Laboratory-based questionnaire and interview administration.
Forty frequent gamblers (22 non-pathological gamblers, 18 pathological gamblers) were recruited from the community.
The SNA revealed significant social network compositional differences between the two groups: pathological gamblers (PGs) had more gamblers, smokers, and drinkers in their social networks than did nonpathological gamblers (NPGs). PGs had more individuals in their network with whom they personally gambled, smoked, and drank with than those with who were NPG. Network ties were closer to individuals in their networks who gambled, smoked, and drank more frequently. Associations between gambling severity and structural network characteristics were not significant.
Pathological gambling is associated with compositional but not structural differences in social networks. Pathological gamblers differ from non-pathological gamblers in the number of gamblers, smokers, and drinkers in their social networks. Homophily within the networks also indicates that gamblers tend to be closer with other gamblers. This homophily may serve to reinforce addictive behaviors, and may suggest avenues for future study or intervention.
PMCID: PMC3578111  PMID: 23072641
Pathological gambling; social network analysis; egocentric; alcohol; tobacco
15.  Living in the Here and Now: Interrelationships between Impulsivity, Mindfulness, and Alcohol Misuse 
Psychopharmacology  2011;219(2):10.1007/s00213-011-2573-0.
Impulsivity and mindfulness both emphasize orientation to the present, and both have been linked to alcohol misuse, but the relationship between the two is not clearly understood.
To examine the relationships between elements of impulsivity and mindfulness, and to examine both variables in relation to alcohol misuse.
Young adults (N = 116) were assessed for alcohol use, mindfulness, and impulsivity using psychometrically validated measures.
Numerous significant associations were present among the facets of impulsivity and mindfulness. The variable most substantially associated with alcohol misuse was Negative Urgency (NU; i.e., proneness to act out under conditions of negative affect). After controlling for other variables, Negative Urgency (NU), Positive Urgency (PU), and delay discounting (DD) were significantly related to alcohol consumption. When examining drinking related consequences, only Lack of Premeditation (LoP) and Negative Urgency (NU) were significant associated.
There was considerable overlap between some elements of impulsivity and mindfulness while the overlap was negligible for other facets. The associations between mindfulness and alcohol misuse were entirely a function of impulsivity. In particular, acting on impulses while experiencing negative affect was significantly associated with level of alcohol consumption and level of alcohol-related risk. Steep discounting of future rewards was associated with alcohol consumption while poor premeditation was associated with adverse drinking consequences. These findings illustrate the importance of jointly studying impulsivity when examining purported effects of mindfulness traits.
PMCID: PMC3881594  PMID: 22169883
Alcohol; Impulsivity; Mindfulness; Delay Discounting; Urgency
16.  Integrating Behavioral Economics and Behavioral Genetics: Delayed Reward Discounting as an Endophenotype for Addictive Disorders 
Delayed reward discounting is a behavioral economic index of impulsivity, referring to how much an individual devalues a reward based on its delay in time. As a behavioral process that varies considerably across individuals, delay discounting has been studied extensively as a model for self-control, both in the general population and in clinical samples. There is growing interest in genetic influences on discounting and, in particular, the prospect of discounting as an endophenotype for addictive disorders (i.e., a heritable mechanism partially responsible for conferring genetic risk). This review assembles and critiques the evidence supporting this hypothesis. Via numerous cross-sectional studies and a small number of longitudinal studies, there is considerable evidence that impulsive discounting is associated with addictive behavior and appears to play an etiological role. Moreover, there is increasing evidence from diverse methodologies that impulsive delay discounting is temporally stable, heritable, and that elevated levels are present in nonaffected family members. These findings suggest that impulsive discounting meets the criteria for being considered an endophenotype. In addition, recent findings suggest that genetic variation related to dopamine neurotransmission is significantly associated with variability in discounting preferences. A significant caveat, however, is that the literature is modest in some domains and, in others, not all the findings have been supportive or consistent. In addition, important methodological considerations are necessary in future studies. Taken together, although not definitive, there is accumulating support for the hypothesis of impulsive discounting as an endophenotype for addictive behavior and a need for further systematic investigation.
PMCID: PMC3881595  PMID: 23344986
Delay Discounting; Impulsivity; Behavioral Economics; Genetics; Addiction; Substance Dependence; Review
Addictive behaviors  2012;38(1):1431-1434.
Impulsivity and risk-taking propensity are neurobehavioral traits that reliably distinguish between smoking and non-smoking adults. However, how these traits relate to smoking quantity and nicotine dependence among older adolescent smokers is unclear. The current study examined impulsivity and risk-taking propensity in relation to smoking behavior and nicotine dependence among current older adolescent smokers (age 16–20 years; N = 107). Participants completed the Barratt Impulsiveness Scale–11 (BIS-11), the Balloon Analogue Risk Task (BART), and self-report measures of smoking behavior and nicotine dependence. Results indicated a significant positive relationship between nicotine dependence and the Attention subscale (β =.20, t = 2.07, p <.05) and the Non-planning subscale (β =.19, t=1.92, p<.06) of the BIS-11. Contrary to expectation, the results also indicated a significant negative relationship between performance on the BART and nicotine dependence (β = −.19, t=−2.18, p <.05), such that greater risk-taking propensity was associated with less dependence. These data suggest that impulsivity and risk-taking propensity are related to older adolescent smoking but are separable traits with distinguishable associations to nicotine dependence among adolescents. These findings support the notion that impulsivity is related to heightened nicotine dependence, but suggest the relationship between risk-taking propensity and nicotine dependence is more ambiguous and warrants further investigation.
PMCID: PMC3493878  PMID: 23006247
older adolescent smoking; impulsivity; risk-taking; nicotine dependence
18.  Subjective Response to Alcohol among Alcohol Dependent Individuals: Effects of the Mu-Opioid Receptor (OPRM1) Gene and Alcoholism Severity 
Subjective response to alcohol has been examined as a marker of alcoholism risk. The A118G single nucleotide polymorphism (SNP) of the mu opioid receptor (OPRM1) gene has been previously associated with subjective response to alcohol in heavy drinkers. The present study seeks to extend the literature by examining the effect of OPRM1 genotype on responses to alcohol in a sample of alcohol dependent individuals. A secondary aim of this study is to examine alcoholism severity as a predictor of subjective responses to alcohol.
Non-treatment seeking problem drinkers (n = 295) were assessed in the laboratory for clinical dimensions of alcohol dependence. Following prospective genotyping, 43 alcohol dependent individuals across the two genotype conditions (AA, n = 23 and AG/GG, n = 20) were randomized to two intravenous infusion sessions, one of alcohol (target BrAC = 0.06 g/dl) and one of saline. Measures of subjective responses to alcohol were administered in both infusion sessions.
Alcohol dependent G-allele carriers reported greater alcohol-induced stimulation, vigor, and positive mood, as compared to A-allele homozygotes. There was no genotype effect on alcohol-induced sedation or craving. There was a statistical trend-level severity × alcohol interaction such that individuals at higher levels of severity reported greater alcohol-induced tension reduction.
These results support the hypothesis that OPRM1 genotype moderates the hedonic effects of alcohol, but not the sedative and unpleasant effects of alcohol, in a sample of alcohol dependent patients. Results are discussed in light of a clinical neuroscience framework to alcoholism.
PMCID: PMC3548029  PMID: 23240711
alcohol dependence; responses to alcohol; genetics; OPRM1; A118G SNP; endophenotype
19.  Symptoms of Depression and PTSD are Associated with Elevated Alcohol Demand 
Drug and alcohol dependence  2012;127(0):129-136.
Behavioral economic demand curves measure individual differences in motivation for alcohol and have been associated with problematic patterns of alcohol use, but little is known about the variables that may contribute to elevated demand. Negative visceral states have been theorized to increase demand for alcohol and to contribute to excessive drinking patterns, but little empirical research has evaluated this possibility. The present study tested the hypothesis that symptoms of depression and PTSD would be uniquely associated with elevated alcohol demand even after taking into account differences in typical drinking levels.
An Alcohol Purchase Task (APT) was used to generate a demand curve measure of alcohol reinforcement in a sample of 133 college students (50.4% male, 64.4% Caucasian, 29.5% African-American) who reported at least one heavy drinking episode (5/4 or more drinks in one occasion for a man/woman) in the past month. Participants also completed standard measures of alcohol consumption and symptoms of depression and PTSD.
Regression analyses indicated that symptoms of depression were associated with higher demand intensity (alcohol consumption when price = 0; ΔR2 = .05, p = .002) and lower elasticity (ΔR2 = .04, p = .03), and that PTSD symptoms were associated with all five demand curve metrics (ΔR2 = .04 – .07, ps < .05).
These findings provide support for behavioral economic models of addiction that highlight the role of aversive visceral states in increasing the reward value of alcohol and provide an additional theoretical model to explain the association between negative affect and problematic drinking patterns.
PMCID: PMC3775331  PMID: 22809894
behavioral economics; alcohol abuse; reinforcement; demand curve; comorbidity
20.  High-resolution Behavioral Economic Analysis of Cigarette Demand to Inform Tax Policy 
Addiction (Abingdon, England)  2012;107(12):2191-2200.
Novel methods in behavioral economics permit the systematic assessment of the relationship between cigarette consumption and price. Toward informing tax policy, the goals of this study were to conduct a high-resolution analysis of cigarette demand in a large sample of adult smokers and to use the data to estimate the effects of tax increases in ten U.S. States.
In-person descriptive survey assessment.
Academic departments at three universities.
Adult daily smokers (i.e., 5+ cigarettes/day; 18+ years old; ≥8th grade education); N = 1056.
Estimated cigarette demand, demographics, expired carbon monoxide.
The cigarette demand curve exhibited highly variable levels of price sensitivity, especially in the form of ‘left-digit effects’ (i.e., very high price sensitivity as pack prices transitioned from one whole number to the next; e.g., $5.80-$6/pack). A $1 tax increase in the ten states was projected to reduce the economic burden of smoking by an average of $531M (range: $93.6M-$976.5M) and increase gross tax revenue by an average of 162% (range: 114%- 247%).
Tobacco price sensitivity is nonlinear across the demand curve and in particular for pack-level left-digit price transitions. Tax increases in U.S. states with similar price and tax rates to the sample are projected to result in substantial decreases in smoking-related costs and substantial increases in tax revenues.
PMCID: PMC3504189  PMID: 22845784
Nicotine Dependence; Cigarette Demand; Behavioral Economics; Tax Policy
21.  Behavioral Economic Analysis of Withdrawal- and Cue-Elicited Craving for Tobacco: An Initial Investigation 
Nicotine & Tobacco Research  2012;14(12):1426-1434.
The role of craving in nicotine dependence remains controversial and may be a function of measurement challenges. The current study used behavioral economic approach to test the hypotheses that subjective craving from acute withdrawal and exposure to tobacco cues dynamically increases the relative value of cigarettes.
Using a 2 (1-hr/12-hr deprivation) × 2 (neutral/tobacco cues) within-subjects design, 33 nicotine dependent adults completed 2 laboratory sessions. Assessment included subjective craving and behavioral economic indices of cigarette demand, namely Intensity (i.e., cigarette consumption at zero cost), O max (i.e., maximum total expenditure), Breakpoint (i.e., highest acceptable price for cigarettes), P max (i.e., price at which consumption becomes sensitive to price), and elasticity (i.e., price sensitivity). Behavioral economic indices were generated using a Cigarette Purchase Task in which participants selected between cigarettes for a subsequent 2-hr self-administration period and money.
Main effects of deprivation and tobacco cues were present for subjective craving and multiple behavioral economic indices of cigarette demand. Interestingly, deprivation significantly increased Breakpoint (p ≤ .01) and P max (p ≤ .05) and had trend-level effects on Intensity and O max (p ≤ .10); whereas cues significantly reduced elasticity (p ≤ .01), reflecting lower sensitivity to increasing prices. Heterogeneous associations were evident among the motivational variables but with aggregations suggesting variably overlapping motivational channels.
These findings further support a behavioral economic approach to craving and a multidimensional conception of acute motivation for addictive drugs. Methodological considerations, including potential order effects, and the need for further refinement of these findings are discussed.
PMCID: PMC3509008  PMID: 22416117
22.  Latent factor structure of a behavioral economic cigarette demand curve in adolescent smokers 
Addictive behaviors  2012;37(11):1257-1263.
Behavioral economic demand curves, or quantitative representations of drug consumption across a range of prices, have been used to assess motivation for a variety of drugs. Such curves generate multiple measures of drug demand that are associated with cigarette consumption and nicotine dependence. However, little is known about the relationships among these facets of demand. The aim of the study was to quantify these relationships in adolescent smokers by using exploratory factor analysis to examine the underlying structure of the facets of nicotine incentive value generated from a demand curve measure. Participants were 138 adolescent smokers who completed a hypothetical cigarette purchase task, which assessed estimated cigarette consumption at escalating levels of price/cigarette. Demand curves and five facets of demand were generated from the measure: Elasticity (i.e., 1/α or proportionate price sensitivity); Intensity (i.e., consumption at zero price); Omax (i.e., maximum financial expenditure on cigarettes); Pmax (i.e., price at which expenditure is maximized); and Breakpoint (i.e., the price that suppresses consumption to zero). Principal components analysis was used to examine the latent structure among the variables. The results revealed a two-factor solution, which were interpreted as “Persistence,” reflecting insensitivity to escalating price, and “Amplitude,” reflecting the absolute levels of consumption and price. These findings suggest a two factor structure of nicotine incentive value as measured via a demand curve. If supported, these findings have implications for understanding the relationships among individual demand indices in future behavioral economic studies and may further contribute to understanding of the nature of cigarette reinforcement.
PMCID: PMC3597467  PMID: 22727784
tobacco; smoking; adolescents; behavioral economics; reinforcement; demand curve; nicotine dependence; motivation
23.  Understanding Naltrexone Mechanism of Action and Pharmacogenetics in Asian Americans via Behavioral Economics: A Preliminary Study 
A behavioral economic approach to understanding the relative value of alcohol may be useful for advancing medication development for alcoholism. Naltrexone is a heavily researched and moderately effective treatment for alcohol dependence making it a good candidate for a proof-of-concept study of behavioral economics and alcoholism pharmacotherapy.
This study examines naltrexone efficacy and pharmacogenetics in terms of the relative value of alcohol, assessed via demand curve analysis.
Materials and Methods
Participants were 35 heavy drinking (AUDIT ≥ 8) Asian Americans. A within-subjects cross-over medication design was used along with an intravenous alcohol challenge completed after four days of both naltrexone and placebo. At baseline and BrAC = 0.06 g/dl, participants completed an Alcohol Purchase Task, which assessed estimated alcohol consumption along escalating prices. Behavioral economic demand curve analysis yielded measures of Intensity, Elasticity, maximum expenditure (Omax), proportionate price insensitivity (Pmax) and breakpoint.
Compared to placebo, naltrexone significantly reduced Intensity, Omax and breakpoint. There were also a trend level medication effects on Pmax. BrAC was associated with increases in Pmax and breakpoint. A significant naltrexone × OPRM1 genotype interaction was observed for intensity of demand.
The present study extends the literature on naltrexone’s mechanisms through the application of a novel behavioral economic paradigm. These results indicate that naltrexone reduces several indices of demand for alcohol. This preliminary report provides further evidence for the effectiveness of naltrexone and supports the utility of a behavioral economic approach to alcoholism pharmacotherapy development.
PMCID: PMC3741097  PMID: 22429255
Alcohol; Naltrexone; Behavioral Economics; Asian Americans
24.  Polymorphisms of the µ-opioid receptor and dopamine D4 receptor genes and subjective responses to alcohol in the natural environment 
Journal of abnormal psychology  2010;119(1):115-125.
Polymorphisms of the µ-opioid receptor (OPRM1) and dopamine D4 receptor (DRD4) genes are associated with subjective responses to alcohol and urge to drink under laboratory conditions. This study examines these associations in the natural environment using ecological momentary assessment (EMA). Participants were non-treatment seeking heavy drinkers (n = 112, 52% female, 61% alcohol dependent) who enrolled in a study of naltrexone effects on craving and drinking in the natural environment. Data were culled from five consecutive days of drinking reports prior to medication randomization. Analyses revealed that, after drinking, carriers of the Asp40 allele of the OPRM1 gene reported higher overall levels of vigor and lower levels negative mood, as compared to homozygotes for the Asn40 variant. Carriers of the long allele (i.e., ≥ 7 tandem repeats) of the DRD4 endorsed greater urge to drink than homozygotes for the short allele. Effects of OPRM1 and DRD4 VNTR genotypes appear to be alcohol dose-dependent. Specifically, carriers of the DRD4-L allele reported slight decreases in urge to drink at higher levels of estimated Blood Alcohol Concentration (eBAC) and Asp40 carriers reported decreases in vigor and increases in negative mood as eBAC rose, as compared to carriers of the major allele for each gene. Self-reported vigor and urge to drink were positively associated with alcohol consumption within the same drinking episode. This study extends findings on subjective intoxication, urge to drink, and their genetic bases from controlled laboratory to naturalistic settings.
PMCID: PMC3703617  PMID: 20141248
OPRM1; DRD4; urge to drink; alcohol; EMA
25.  A preliminary pharmacogenetic investigation of adverse events from topiramate in heavy drinkers 
Topiramate, an anticonvulsant medication, is an efficacious treatment for alcohol dependence. To date, little is known about genetic moderators of side effects from topiramate. The objective of this study was to examine three single nucleotide polymorphisms (SNPs) of the glutamate receptor GluR5 gene (GRIK1) as predictors of topiramate-induced side effects in the context of a laboratory study of topiramate. Heavy drinkers (n = 51, 19 females), 75% of whom met criteria for an alcohol use disorder, completed a 5-week dose escalation schedule to a target dose of either 200 or 300 mg, or matched placebo. The combined medication groups were compared to placebo-treated individuals for side effects at target dose. Analyses revealed that a SNP in intron 9 of the GRIK1 gene (rs2832407) was associated with the severity of topiramate-induced side effects and with serum levels of topiramate. Genes underlying glutamatergic neurotransmission, such as the GRIK1 gene, may help predict heterogeneity in topiramate-induced side effects. Future studies in larger samples are needed to more fully establish these preliminary findings.
PMCID: PMC3682424  PMID: 19331489

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