Stephen A. Lisman

Examining impulsivity as an endophenotype using a behavioral approach: a DRD2 TaqI A and DRD4 48-bp VNTR association study

BackgroundResearch on the genetic basis for impulsivity has revealed an array of ambiguous findings. This may be a result of limitations to self-report assessments of impulsivity. Behavioral measures that assess more narrowly defined aspects of impulsivity may clarify genetic influences. This study examined the relationship between possession of the DRD2 TaqI A and DRD4 48 bp VNTR genetic polymorphisms and performance on a behavioral measure of impulsivity, the delay discounting task (DDT), and three traditional self-report measures.Methods195 individuals (42% male) were recruited from a university campus and were assessed in small group sessions using personal computers. Genotyping was conducted using previously established protocols. For the DRD2 TaqI A locus, individuals were designated as possessing at least one copy of the A1 allele (A1+) or not (A1-), and for the DRD4 48-bp VNTR locus, individuals were designated as having at least one long allele (7 repeats or longer, L+) or not (L-). Principal analyses used multiple univariate factorial 2 (A1+/A1-) × 2 (L+/L-) analyses of variance.ResultsA significant main effect of A1+ status on DDT performance was evident (p = .006) as well as a significant interaction effect (p = .006) between both genes. No other significant effects were evident on the self-report measures, with the exception of a trend toward an interaction effect on the Sensation Seeking Scale. Exploratory analyses suggested that the significant effects were not a function of population stratification or gender.DiscussionThese data suggest that the DRD2 TaqI A and DRD4 VNTR polymorphisms influence impulsivity as measured with a delay discounting task. Specifically, these findings suggest that an interaction between the functional effects of the two unlinked genotypes results in significant difference in the balance of mesolimbic dopaminergic activation relative to frontal-parietal activation. However, these findings are also the first in this area and must be replicated.ConclusionThese findings suggest a meaningful interaction between the DRD2 TaqI A and DRD4 VNTR polymorphisms in the expression of impulsivity and provide initial support for the utility of using behavioral measures for clarifying genetic influences on impulsivity.

Further validation of a cigarette purchase task for assessing the relative reinforcing efficacy of nicotine in college smokers.

The authors sought to further validate a cigarette purchase task (CPT), a self-report analogue of a progressive-ratio operant schedule, for the assessment of the relative reinforcing efficacy (RRE) of nicotine in smokers. The measure was assessed in terms of its correspondence to typically observed operant behavior, convergent validity, and divergent validity. Participants were 33 individuals (58% male, age M = 19.30 years) who smoked at least weekly (M = 5.31 cigarettes/day) and underwent a single assessment session. Data from the CPT exhibited the predicted inverse relationship between consumption and price, the predicted relationship between consumption and expenditure, and a heterogeneous pattern of interrelationships among the indices of reinforcement. In addition, 2 indices from the measure, intensity of demand and maximum expenditure for cigarettes, exhibited robust convergent and divergent validity. Although this is an incipient research area and the current study used a relatively small sample, these findings support the validity of a CPT as a time- and cost-efficient method for assessing nicotine reinforcement. Theoretical implications of the findings, limitations, and future directions are also discussed.

An exposure-based examination of the effects of written emotional disclosure.

OBJECTIVES: We undertook this study to clarify the operative mechanisms that account for the relationship between emotional disclosure and health. We hypothesized that emotional disclosure via writing was a form of exposure-based therapy and that exposure was the active therapeutic component. Design and method. A group of 129 male and female undergraduates were randomly assigned to three writing groups: (1) a trauma disclosure writing group; (2) a positive emotion writing group to control for affect arousal; and (3) a neutral writing group to control for any affect arousal - either positive or negative. Process measures were taken before and after each 3-day, 20-minute writing session. All participants completed questionnaires that assessed psychological and physical functioning at both the baseline and the end of the semester (approximately 9 weeks later). RESULTS: Groups reported differential affective arousal as well as disclosure themes in accord with our predictions. We did not replicate the findings of Pennebaker and his colleagues (e.g. Pennebaker & Beall, 1986). In our study, physical health outcome measures did not differ between groups by the end of the semester, nor did psychological measures change from baseline to follow-up. CONCLUSIONS: We found only limited support for the hypothesis that exposure best explains the effects of written self-disclosure. Implications for future research in this area are discussed.

Behavioral economic analysis of cue-elicited craving for alcohol

AIMS Craving as a motivational determinant of drug use remains controversial because of ambiguous empirical findings. A behavioral economic approach may clarify the nature of craving, theorizing that subjective craving functionally reflects an acute increase in a drugs value. The current study tested this hypothesis via a multidimensional assessment of alcohol demand over the course of an alcohol cue reactivity procedure. DESIGN One-way within-subjects design. SETTING Human laboratory environment. PARTICIPANTS Heavy drinkers (n = 92) underwent exposures to neutral (water) cues followed by personalized alcohol cues. ASSESSMENTS Participants were assessed for craving, alcohol demand, affect, and salivation following each exposure. FINDINGS Alcohol versus neutral cues significantly increased craving and multiple behavioral economic measures of the relative value of alcohol, including alcohol consumption under conditions of zero cost (intensity), maximum expenditure on alcohol (O(max)), persistence in drinking to higher prices (breakpoint) and proportionate price insensitivity (normalized P(max)). Craving was significantly correlated with demand measures at levels ranging from 0.21-0.43. CONCLUSIONS These findings support the potential utility of a behavioral economic approach to understanding the role of environmental stimuli in alcohol-related decision making. Specifically, they suggest that the behavioral economic indices of demand may provide complementary motivational information that is related to though not entirely redundant with measures of subjective craving.

Alcohol and social anxiety in males: behavioral, cognitive, and physiological effects.

As a test of the tension reduction hypothesis (TRH) of alcohol consumption, two studies were conducted to determine the effects of alcohol on heterosexual social anxiety. In Study 1 a clinical population of socially anxious males first drank .0 or .5 ml of pure ethanol/kg of body weight and then interacted with a female confederate. Expectancies about alcohol consumption and its effects were manipulated by using both a placebo beverage and instructional sets about the positive or negative effects of alcohol. Physiological, cognitive/selfreport, and behavioral measures indicated that alcohol produced a marked impairment in the shy subjects on a number of behavioral and self-report measures while not appreciably affecting physiological responses. Study 2 employed a sample of undergraduate males and three dosages of alcohol (.0, ,33, and .75 ml/kg). Once again alcohol impaired both behavioral performance and self-report ratings. In addition, the high-dosage alcohol group experienced greater sustained cardiac acceleration as a function of the social interaction than did the other two groups, suggesting the possibility of an alcohol-stress functional relationship. Taken collectively, this sequence of studies disconfirms the utility of a global TRH in explaining the psychological and physiological effects of alcohol ingestion.

Effects of craving and DRD4 VNTR genotype on the relative value of alcohol: an initial human laboratory study

BackgroundCraving for alcohol is a highly controversial subjective construct and may be clarified by Loewensteins visceral theory, which emphasizes cravings behavioral effects on the relative value of alcohol. Based on the visceral theory, this study examined the effects of a craving induction on the relative value of alcohol as measured by a behavioral choice task. In addition, based on previous evidence of its role in the expression of craving, the influence of DRD4 VNTR genotype (DRD4-L vs. DRD4-S) was also examined.MethodsThirty-five heavy drinkers (54% male; 31% DRD4-L) were randomly assigned to receive either a craving induction (exposure to personally relevant alcohol cues) or a control induction (exposure to neutral cues), which was followed by an alcohol-money choice task. Participants were assessed for craving and positive/negative affect throughout the procedure, and relative value of alcohol was derived from participant choices for alcohol versus money. DRD4 VNTR status was assessed retrospectively via buccal samples using previously established protocols.ResultsFactorial analysis of the craving induction revealed that it was associated with significant increase in craving (p < .001), but not greater relative value of alcohol. Factorial analyses including DRD4 VNTR genotype of did not suggest an influence on reactivity to the craving induction, although this analysis was substantially compromised by small cell sample sizes. Continuous analyses revealed that craving was significantly associated with the relative value of alcohol (p < .05) and possession of the DRD4-L allele further amplified this relationship (p < .001).ConclusionThese results are interpreted as generally supporting Loewensteins visceral theory of craving and evidence of a functional role of DRD4 VNTR genotype in the expression of craving for alcohol. Methodological limitations, mechanisms underlying these findings, and future directions are discussed.

Alcohol enhancement of human memory: Tests of consolidation and interference hypotheses

Two hypotheses about the phenomenon of alcoholenhanced human memory were investigated. Whereas a consolidation account of this phenomenon indicates that continued processing of a target memory is facilitated by alcohol, an interference account states that the alcohol main effect is to impair the acquisition of potentially interfering new memories. No support was found for the consolidation view in an experiment manipulating (1) the length of time items preceded drug administration, (2) the amount of postpresentation processing each item received, and (3) the type of memory test employed. In line with expectations derived from interference theory, retention was substantially improved only for recall and not for tests of recognition memory.

Reactivity to alcohol cues: isolating the role of perceived availability.

Perceived availability of a substance has been proposed to play a role in cue reactivity by both traditional classical conditioning models and S. T. Tiffanys (1990) cognitive processing model (CPM) of substance use. This study investigated the role of availability information on alcohol cue reactivity. Subjects were 134 heavy drinkers in a 2 x 2 between-subjects design, crossing cues (alcohol vs. neutral) and availability information (availability vs. unavailability). The results indicated significant main effects for cue type, with alcohol cues eliciting greater reactivity on multiple measures, and an interaction effect on the Alcohol Urge Questionnaire (M. J. Bohn, D. D. Krahn, & B. B. Staehler, 1995), such that exposure to alcohol cues in conjunction with unavailability information elicited a greater urge. This was largely a result of changes in self-reported craving and was interpreted as consistent with the CPM. Alternative methodologies and limitations are discussed.

The effects of mood variation on state-dependent retention

Few studies have examined mood state-dependent retention—the notion that when the affective states accompanying learning and remembering are the same, information will be retained better than when they differ. Three experiments were conducted to examine state-dependent retention using a simple mood induction procedure and an unselected population of college students. Self-statements developed by Velten (1968) were chosen to influence subjects to feel somewhat depressed or elated or to experience no mood change. A 2 ×2 experimental design, incorporating a single word list and varying the mood conditions present during learning and later testing, was used in each of the first two experiments, neither of which revealed state dependence. However, a significant effect was found in the third experiment, which employed an interference paradigm. Subjects learned two lists of words under differing mood conditions. Testing was conducted under one of two mood conditions, elation or depression. Methodological issues and clinical implications of these findings are discussed.

Effects of a context shift and multiple context extinction on reactivity to alcohol cues.

Cue exposure treatment (CET) attempts to reduce the influence of conditioned substance cues on addictive behavior via extinction, but has received only modest empirical support in clinical trials. This may be because extinction learning appears to be context dependent and a change in context may result in a return of conditioned responding (i.e., renewal), although this has received only limited empirical examination. The current study used a 4-session laboratory analogue of CET to examine whether a change in context following 3 sessions of alcohol cue exposure with response prevention would result in renewal of conditioned responding. In addition, this study examined whether conducting extinction in multiple contexts would attenuate renewal of conditioned responding. In one-way between-subjects design, 73 heavy drinkers (71% men) were randomized to 3 conditions: (a) single context extinction (extinction to alcohol cues in the same context for 3 sessions followed by a context shift at the fourth session), (b) multiple context extinction (extinction to alcohol cues in different contexts each day for all 4 sessions), and (c) pseudoextinction control condition (exposure to neutral cues in the same context for 3 sessions followed by exposure to alcohol cues at the fourth session). The results revealed the predicted cue reactivity and extinction effects, but the hypotheses that a context shift would generate renewed cue reactivity and that multiple contexts would enhance extinction were not supported. Methodological aspects of the study and the need for parametric data on the context dependency of extinction to alcohol cues are discussed.