Kelly E. Courtney

Binge drinking in young adults: Data, definitions, and determinants

Binge drinking is an increasingly important topic in alcohol research, but the field lacks empirical cohesion and definitional precision. The present review summarizes findings and viewpoints from the scientific binge-drinking literature. Epidemiological studies quantify the seriousness of alcohol-related problems arising from binge drinking, with a growing incidence reported in college-age men over the last 2 years. Experimental studies have found neurocognitive deficits for frontal lobe processing and working memory operations in binge-drinking compared with nonbinge alcohol drinkers. The findings are organized with the goals of providing a useful binge-drinking definition in the context of the empirical results. Theoretical implications are discussed on how binge drinking may alter neurophysiological and neurocognitive function.

Methamphetamine: An update on epidemiology, pharmacology, clinical phenomenology, and treatment literature

BACKGROUND Despite initial reports of a decline in use in the early 2000s, methamphetamine remains a significant public health concern with known neurotoxic and neurocognitive effects to the user. The goal of this review is to update the literature on methamphetamine use and addiction since its assent to peak popularity in 1990s. METHODS We first review recent epidemiological reports with a focus on methamphetamine accessibility, changes in use and disorder prevalence rates over time, and accurate estimates of the associated burden of care to the individual and society. Second, we review methamphetamine pharmacology literature with emphasis on the structural and functional neurotoxic effects associated with repeated use of the drug. Third, we briefly outline the findings on methamphetamine-related neurocognitive deficits as assessed via behavioral and neuroimaging paradigms. Lastly, we review the clinical presentation of methamphetamine addiction and the evidence supporting the available psychosocial and pharmacological treatments within the context of an addiction biology framework. CONCLUSION Taken together, this review provides a broad-based update of the available literature covering methamphetamine research over the past two decades and concludes with recommendations for future research.

Fronto‐striatal functional connectivity during response inhibition in alcohol dependence

Poor response inhibition has been implicated in the development of alcohol dependence, yet little is known about how neural pathways underlying cognitive control are affected in this disorder. Moreover, endogenous opioid levels may impact the functionality of inhibitory control pathways. This study investigated the relationship between alcohol dependence severity and functional connectivity of fronto‐striatal networks during response inhibition in an alcohol‐dependent sample. A secondary aim of this study was to test the moderating effect of a functional polymorphism (A118G) of the μ‐opioid receptor (OPRM1) gene. Twenty individuals with alcohol dependence (six females; 90% Caucasian; mean age = 29.4) who were prospectively genotyped on the OPRM1 gene underwent blood oxygen level‐dependent functional magnetic resonance imaging while performing a Stop‐Signal Task. The relationship between alcohol dependence severity and functional connectivity within fronto‐striatal networks important for response inhibition was assessed using psychophysiological interaction analyses. Analyses revealed greater alcohol dependence severity was associated with weaker functional connectivity between the putamen and prefrontal regions (e.g. the anterior insula, anterior cingulate and medial prefrontal cortex) during response inhibition. Furthermore, the OPRM1 genotype was associated with differential response inhibition‐related functional connectivity. This study demonstrates that individuals with more severe alcohol dependence exhibit less frontal connectivity with the striatum, a component of cognitive control networks important for response inhibition. These findings suggest that the fronto‐striatal pathway underlying response inhibition is weakened as alcoholism progresses.

Subjective Response to Alcohol Among Alcohol-Dependent Individuals: Effects of the Mu-Opioid Receptor (OPRM1) Gene and Alcoholism Severity

BACKGROUND 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. This 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. METHODS Nontreatment 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 2 genotype conditions (AA, n = 23 and AG/GG, n = 20) were randomized to 2 intravenous infusion sessions: 1 of alcohol (target breath alcohol concentration = 0.06 g/dl) and 1 of saline. Measures of subjective responses to alcohol were administered in both infusion sessions. RESULTS 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. CONCLUSIONS 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.

The Relationship Between Measures of Impulsivity and Alcohol Misuse: An Integrative Structural Equation Modeling Approach

BACKGROUND Higher levels of impulsivity have been implicated in the development of alcohol use disorders. Recent findings suggest that impulsivity is not a unitary construct, highlighted by the diverse ways in which the various measures of impulsivity relate to alcohol use outcomes. This study simultaneously tested the following dimensions of impulsivity as determinants of alcohol use and alcohol problems: risky decision making, self-reported risk-attitudes, response inhibition, and impulsive decision making. METHODS Participants were a community sample of nontreatment seeking problem drinkers (n = 158). Structural equation modeling (SEM) analyses employed behavioral measures of impulsive decision making (delay discounting task [DDT]), response inhibition (stop signal task [SST]), and risky decision making (Balloon Analogue Risk Task [BART]), and a self-report measure of risk-attitudes (domain-specific risk-attitude scale [DOSPERT]), as predictors of alcohol use and of alcohol-related problems in this sample. RESULTS The model fits well, accounting for 38% of the variance in alcohol problems, and identified 2 impulsivity dimensions that significantly loaded onto alcohol outcomes: (i) impulsive decision making, indexed by the DDT; and (ii) risky decision making, measured by the BART. CONCLUSIONS The impulsive decision-making dimension of impulsivity, indexed by the DDT, was the strongest predictor of alcohol use and alcohol pathology in this sample of problem drinkers. Unexpectedly, a negative relationship was found between risky decision making and alcohol problems. The results highlight the importance of considering the distinct facets of impulsivity to elucidate their individual and combined effects on alcohol use initiation, escalation, and dependence.

Binge Drinking Effects on EEG in Young Adult Humans

Young adult (N = 96) university students who varied in their binge drinking history were assessed by electroencephalography (EEG) recording during passive viewing. Groups consisted of male and female non-binge drinkers (>1 to 5/4 drinks/ounces in under two hours), low-binge drinkers (5/4–7/6 drinks/ounces in under two hours), and high-binge drinkers (≥ 10 drinks/ounces in under two hours), who had been drinking alcohol at their respective levels for an average of 3 years. The non- and low-binge drinkers exhibited less spectral power than the high-binge drinkers in the delta (0–4 Hz) and fast-beta (20–35 Hz) bands. Binge drinking appears to be associated with a specific pattern of brain electrical activity in young adults that may reflect the future development of alcoholism.

Neural substrates of cue reactivity: association with treatment outcomes and relapse.

Given the strong evidence for neurological alterations at the basis of drug dependence, functional magnetic resonance imaging (fMRI) represents an important tool in the clinical neuroscience of addiction. fMRI cue‐reactivity paradigms represent an ideal platform to probe the involvement of neurobiological pathways subserving the reward/motivation system in addiction and potentially offer a translational mechanism by which interventions and behavioral predictions can be tested. Thus, this review summarizes the research that has applied fMRI cue‐reactivity paradigms to the study of adult substance use disorder treatment responses. Studies utilizing fMRI cue‐reactivity paradigms for the prediction of relapse and as a means to investigate psychosocial and pharmacological treatment effects on cue‐elicited brain activation are presented within four primary categories of substances: alcohol, nicotine, cocaine and opioids. Lastly, suggestions for how to leverage fMRI technology to advance addiction science and treatment development are provided.

Initial Evidence that OPRM1 Genotype Moderates Ventral and Dorsal Striatum Functional Connectivity During Alcohol Cues

BACKGROUND 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 of the mu-opioid receptor (OPRM1) gene. METHODS Seventeen individuals with alcohol dependence (6 females; 90% Caucasian; mean age = 29.4) underwent blood oxygen level-dependent functional magnetic resonance imaging, while performing an alcohol taste-cues task. Psychophysiological interaction 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. RESULTS Compared to A-allele homozygotes, G-allele carriers of the OPRM1 gene showed (i) greater activation of the insula and orbitofrontal cortex and (ii) stronger negative fronto-striatal functional connectivity for both ventral and dorsal striatal seed regions during processing of alcohol versus water cues. CONCLUSIONS 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.

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

Methamphetamine (MA) use disorder is a serious psychiatric condition for which there are no FDA-approved medications. Naltrexone (NTX) is an opioid receptor antagonist with demonstrated efficacy, albeit moderate, for the treatment of alcoholism and opioid dependence. Preclinical and clinical studies suggest that NTX may be useful for the treatment of MA use disorder. To inform treatment development, we conducted a double-blind, randomized, crossover, placebo-controlled human laboratory study of NTX. Non-treatment-seeking individuals meeting DSM-IV criteria for MA abuse or dependence (n=30) completed two separate 5-day inpatient stays. During each admission, participants completed testing sessions comprised of MA cue-reactivity and intravenous MA administration (30 mg) after receiving oral NTX (50 mg) or placebo for 4 days. This study tested the hypotheses that NTX would (a) attenuate cue-induced MA craving, and (b) reduce subjective responses to MA administration. Results largely supported the study hypotheses such that (a) NTX significantly blunted cue-induced craving for MA and (b) attenuated several of the hedonic subjective effects of MA, including craving, during controlled MA administration and as compared with placebo. NTX decreased overall subjective ratings of ‘crave drug,’ ‘stimulated,’ and ‘would like drug access,’ decreased the the post-MA administration timecourse of ‘anxious’ and increased ratings of ‘bad drug effects,’ as compared with placebo. These findings support a potential mechanism of action by showing that NTX reduced cue-induced craving and subjective responses to MA. This is consistent with positive treatment studies of NTX for amphetamine dependence, as well as ongoing clinical trials for MA.

The Association between Cue-Reactivity in the Precuneus and Level of Dependence on Nicotine and Alcohol

BACKGROUND Given numerous reports implicating involvement of the precuneus in cue-reactivity paradigms, the goal of this investigation was to examine the relationship between activation of the precuneus in response to drug cues and measures of subjective craving and severity of dependence in volunteers who were comorbid for alcohol and nicotine abuse. METHODS Forty research participants, who all reported heavy drinking and daily smoking, were recruited (15 women; 70% Caucasian; mean age=31.2 years) for a functional magnetic resonance imaging (fMRI) session involving a cigarette video-cues task and an alcohol taste-cues task. Mean precuneus activation from both tasks during cue presentation was subjected to bivariate correlation analyses with indices of dependence severity and subjective craving. RESULTS Precuneus activation in the contrast of Cigarette Cues vs. Control Cues was positively correlated with scores on the Fagerström Test of Nicotine Dependence (r=0.389, p=0.016), and activation in the Alcohol Cues vs. Control Cues contrast was positively correlated with Alcohol Dependence Scale scores (r=0.338, p=0.038). No correlations with subjective craving were observed (ps>0.05). CONCLUSIONS These findings indicate that the precuneus is involved in cue reactivity for both cigarettes and alcohol, and that this involvement is moderated by severity of drug dependence. The precuneus may be a cortical locus for neuroplastic changes related to drug dependence.