Robert F. Leeman

Understanding the construct of impulsivity and its relationship to alcohol use disorders

There are well‐established links between impulsivity and alcohol use in humans and other model organisms; however, the etiological nature of these associations remains unclear. This is likely due, in part, to the heterogeneous nature of the construct of impulsivity. Many different measures of impulsivity have been employed in human studies, using both questionnaire and laboratory‐based tasks. Animal studies also use multiple tasks to assess the construct of impulsivity. In both human and animal studies, different measures of impulsivity often show little correlation and are differentially related to outcome, suggesting that the impulsivity construct may actually consist of a number of more homogeneous (and potentially more meaningful) subfacets. Here, we provide an overview of the different measures of impulsivity used across human and animal studies, evidence that the construct of impulsivity may be better studied in the context of more meaningful subfacets, and recommendations for how research in this direction may provide for better consilience between human and animal studies of the connection between impulsivity and alcohol use.

Similarities and Differences between Pathological Gambling and Substance Use Disorders: A Focus on Impulsivity and Compulsivity

RationalePathological gambling (PG) has recently been considered as a “behavioral” or nonsubstance addiction. A comparison of the characteristics of PG and substance use disorders (SUDs) has clinical ramifications and could help advance future research on these conditions. Specific relationships with impulsivity and compulsivity may be central to understanding PG and SUDs.ObjectivesThis review was conducted to compare and contrast research findings in PG and SUDs pertaining to neurocognitive tasks, brain function, and neurochemistry, with a focus on impulsivity and compulsivity.ResultsMultiple similarities were found between PG and SUDs, including poor performance on neurocognitive tasks, specifically with respect to impulsive choice and response tendencies and compulsive features (e.g., response perseveration and action with diminished relationship to goals or reward). Findings suggest dysfunction involving similar brain regions, including the ventromedial prefrontal cortex and striatum and similar neurotransmitter systems, including dopaminergic and serotonergic. Unique features exist which may in part reflect influences of acute or chronic exposures to specific substances.ConclusionsBoth similarities and differences exist between PG and SUDs. Understanding these similarities more precisely may facilitate treatment development across addictions, whereas understanding differences may provide insight into treatment development for specific disorders. Individual differences in features of impulsivity and compulsivity may represent important endophenotypic targets for prevention and treatment strategies.

A targeted review of the neurobiology and genetics of behavioural addictions: an emerging area of research.

This review summarizes neurobiological and genetic findings in behavioural addictions, draws parallels with findings pertaining to substance use disorders, and offers suggestions for future research. Articles concerning brain function, neurotransmitter activity, and family history and (or) genetic findings for behavioural addictions involving gambling, Internet use, video game playing, shopping, kleptomania, and sexual activity were reviewed. Behavioural addictions involve dysfunction in several brain regions, particularly the frontal cortex and striatum. Findings from imaging studies incorporating cognitive tasks have arguably been more consistent than cue-induction studies. Early results suggest white and grey matter differences. Neurochemical findings suggest roles for dopaminergic and serotonergic systems, but results from clinical trials seem more equivocal. While limited, family history and genetic data support heritability for pathological gambling and that people with behavioural addictions are more likely to have a close family member with some form of psychopathology. Parallels exist between neurobiological and genetic and family history findings in substance and nonsubstance addictions, suggesting that compulsive engagement in these behaviours may constitute addictions. To date, findings are limited, particularly for shopping, kleptomania, and sexual behaviour. Genetic understandings are at an early stage. Future research directions are offered.

Ethanol consumption: how should we measure it? Achieving consilience between human and animal phenotypes.

There is only modest overlap in the most common alcohol consumption phenotypes measured in animal studies and those typically studied in humans. To address this issue, we identified a number of alcohol consumption phenotypes of importance to the field that have potential for consilience between human and animal models. These phenotypes can be broken down into three categories: (1) abstinence/the decision to drink or abstain; (2) the actual amount of alcohol consumed; and (3) heavy drinking. A number of suggestions for human and animal researchers are made in order to address these phenotypes and enhance consilience. Laboratory studies of the decision to drink or to abstain are needed in both human and animal research. In human laboratory studies, heavy or binge drinking that meets cut‐offs used in epidemiological and clinical studies should be reported. Greater attention to patterns of drinking over time is needed in both animal and human studies. Individual differences pertaining to all consumption phenotypes should be addressed in animal research. Lastly, improved biomarkers need to be developed in future research for use with both humans and animals. Greater precision in estimating blood alcohol levels in the field, together with consistent measurement of breath/blood alcohol levels in human laboratory and animal studies, provides one means of achieving greater consilience of alcohol consumption phenotypes.

The BRENDA model: integrating psychosocial treatment and pharmacotherapy for the treatment of alcohol use disorders.

While the U.S. Food and Drug Administration has approved several medications for the treatment of alcohol-related problems, their use has not gained wide acceptance in the United States. Typically, patients with alcohol use disorders are only referred to psychosocial support (e.g., Alcoholics Anonymous). However, the use of pharmacotherapy may complement psychosocial treatments, as evidence shows that pharmacotherapy can improve treatment outcomes. The effectiveness of pharmacotherapy depends on patient compliance with taking the medication and the context in which the medication is administered. BRENDA is a psychosocial program designed specifically to be used by many types of healthcare providers, including primary care clinicians. Designed to enhance medication and treatment compliance, BRENDA is an ideal approach for use in conjunction with pharmacotherapy. The BRENDA approach has 6 components: 1) a biopsychosocial evaluation; 2) a report of findings from the evaluation given to the patient; 3) empathy; 4) addressing patient needs; 5) providing direct advice; and 6) assessing patient reaction to advice and adjusting the treatment plan as needed. This paper describes these components and discusses how the empirical support for each component is linked to the enhancement of medication compliance and the improvement of treatment outcomes.

Risk factors for treatment failure in smokers: Relationship to alcohol use and to lifetime history of an alcohol use disorder

Little is known about the impact of alcohol involvement on smoking cessation relapse or possible mechanisms for these associations. We addressed these issues using data from a randomized clinical trial of two types of framed messages (gain vs. loss) in conjunction with open label sustained-release (SR) bupropion (Toll et al., 2007) (N = 249). Participants were categorized according to whether or not they were diagnosed with a lifetime alcohol use disorder (AUD; i.e., current or past alcohol abuse or past alcohol dependence) and according to three levels of alcohol use: abstinence, moderate, or hazardous use. Alcohol use categories were established for drinking at baseline, during the 6-week treatment period and through 12 weeks post-quit. There were few significant differences by baseline alcohol use level or AUD history for a series of predictors of smoking cessation failure (e.g., depressive symptoms). During treatment and follow-up, the probability of any smoking on heavy drinking days was significantly higher than the probability of smoking on moderate drinking or abstinent days. AUD history did not predict smoking cessation relapse in any analysis, nor were any alcohol usexAUD history interactions significant. Moderate alcohol users and, to a lesser extent, abstainers from alcohol at baseline were less likely than hazardous drinkers to have relapsed at 12 weeks post-quit. Based on these findings, it appears that risk of any smoking and of relapse was associated primarily with heavy drinking days and a hazardous pattern of use respectively, rather than with moderate drinking.

Impulsivity, Sensation-Seeking, and Part-Time Job Status in Relation to Substance Use and Gambling in Adolescents

PURPOSE Although impulsivity, sensation-seeking, and part-time employment have each been linked to risky behaviors in adolescents, their inter-relationships are less well-understood. We examined data from adolescents to assess the following predictions: (1) sensation-seeking would relate closely to substance use and gambling; (2) impulsivity would relate closely to alcohol, drug, and gambling problems; and (3) these relationships would be particularly strong among those holding part-time jobs. METHOD High-school students (N = 3,106) were surveyed to provide data on impulsivity, sensation-seeking, and part-time job status. Bivariate and logistic regression analyses were conducted to examine relationships with gambling, substance use (i.e., alcohol, cigarettes, and marijuana) and related problems. RESULTS Both impulsivity and sensation-seeking related significantly to substance use and impulsivity to gambling. Impulsivity had stronger associations with drug and gambling problems than sensation-seeking did. Students with paid part-time jobs were more likely to drink alcohol, binge drink, and use marijuana. Sensation-seeking had a particularly strong relationship to heavy cigarette smoking among students with part-time jobs. Conversely, there was little relationship between part-time job status and smoking among low sensation-seekers. CONCLUSIONS These findings further support the relevance of sensation-seeking, impulsivity, and part-time job status to risky behaviors among adolescents. Sensation-seeking and impulsivity had unique relationships to risky behaviors, in accordance with theory and prior evidence. Impulsive adolescents may be in particular need for interventions to reduce drug use and gambling. Although part-time jobs can be beneficial, parents and caregivers should be mindful of potential negative ramifications of paid work outside the home.

Alcohol-induced disinhibition expectancies and impaired control as prospective predictors of problem drinking in undergraduates

Trait disinhibition is associated with problem drinking and alcohol drinking can bring about a state of disinhibition. It is unclear however, if expectancies of alcohol-induced disinhibition are unique predictors of problem drinking. Impaired control (i.e., difficulty in limiting alcohol consumption) may be related to disinhibition expectancies in that both involve issues of control related to alcohol use. Data from a prospective survey of undergraduates assessed during freshman (N = 337) and senior year (N = 201) were analyzed to determine whether subscales of the Drinking-Induced Disinhibition Scale (Leeman, Toll, & Volpicelli, 2007) and the Impaired Control Scale (Heather et al., 1993) predicted unique variance in heavy episodic drinking and alcohol-related problems. In Time 1 cross-sectional models, Dysphoric disinhibition expectancies predicted alcohol-related problems and impaired control predicted both alcohol-related problems and heavy episodic drinking. In prospective models, Time 1 impaired control predicted Time 2 alcohol-related problems and Time 1 Euphoric/social Disinhibition expectancies predicted Time 2 heavy episodic drinking. These findings suggest that expectancies of alcohol-induced disinhibition and impaired control predict unique variance in problem drinking cross-sectionally and prospectively, and that these phenomena should be targeted in early intervention efforts.

A critical review of the literature on attentional bias in cocaine use disorder and suggestions for future research.

Cocaine use disorder (CUD) continues to be an important public health problem, and novel approaches are needed to improve the effectiveness of treatments for CUD. Recently, there has been increased interest in the role of automatic cognition such as attentional bias (AB) in addictive behaviors, and AB has been proposed to be a cognitive marker for addictions. Automatic cognition may be particularly relevant to CUD, as there is evidence for particularly robust AB to cocaine cues and strong relationships to craving for cocaine and other illicit drugs. Further, the wide-ranging cognitive deficits (e.g., in response inhibition and working memory) evinced by many cocaine users enhance the potential importance of interventions targeting automatic cognition in this population. In the current article, we discuss relevant addiction theories, followed by a review of studies that examined AB in CUD. We then consider the neural substrates of AB, including human neuroimaging, neurobiological, and pharmacological studies. We conclude with a discussion of research gaps and future directions for AB in CUD.

Dose Dependent Reduction of Hazardous Alcohol Use in a Placebo-Controlled Trial of Naltrexone for Smoking Cessation

The opiate antagonist naltrexone (Ntx) has demonstrated efficacy in the treatment of alcohol dependence and as a component of treatment to reduce heavy drinking. At present, there are no published dose-ranging clinical trials of the oral preparation for treatment of problem drinking. The present study evaluated the effects of Ntx on alcohol use among the subset of hazardous drinkers (n=102) who participated in a placebo-controlled, dose-ranging trial of oral Ntx (25-mg, 50-mg and 100-mg doses) combined with open-label transdermal nicotine patch for enhancing smoking cessation. On the primary outcome--no hazardous drinking (drinking that exceeded weekly or daily limits) during treatment--25 mg and 50 mg Ntx were superior to placebo (each p<0.05). These findings remained after controlling for baseline predictors or smoking abstinence during treatment. Time to remission of hazardous drinking was examined as a secondary outcome with definitions of hazardous drinking based on weekly limits, daily limits and the combination of weekly and daily limits and the results were consistent with the primary findings. In conclusion, the findings suggest that Ntx can reduce the risk of hazardous drinking in smokers who are not seeking or receiving alcohol treatment, providing strong evidence for the pharmacological effects of Ntx on drinking. This effect appears to favour lower doses that may be better tolerated and less expensive than the higher 100-mg dose. Given its efficacy and favourable side-effect profile, the 25-mg dose should be considered for future studies of combination therapy.