Robert Miranda

Adolescence: Booze, Brains, and Behavior

This article represents the proceedings of a symposium at the 2004 Research Society on Alcoholism meeting in Vancouver, British Columbia, Canada, organized and chaired by Peter M. Monti and Fulton T. Crews. The presentations and presenters were (1) Introduction, by Peter M. Monti; (2) Adolescent Binge Drinking Causes Life-Long Changes in Brain, by Fulton T. Crews and Kim Nixon; (3) Functional Neuroimaging Studies in Human Adolescent Drinkers, by Susan F. Tapert; (4) Abnormal Emotional Reactivity as a Risk Factor for Alcoholism, by Robert Miranda, Jr.; (5) Alcohol-Induced Memory Impairments, Including Blackouts, and the Changing Adolescent Brain, by Aaron M. White and H. Scott Swartzwelder; and (6) Discussion, by Kenneth Sher.

Alcohol demand, delayed reward discounting, and craving in relation to drinking and alcohol use disorders

A behavioral economic approach to alcohol use disorders (AUDs) emphasizes both individual and environmental determinants of alcohol use. The current study examined individual differences in alcohol demand (i.e., motivation for alcohol under escalating conditions of price) and delayed reward discounting (i.e., preference for immediate small rewards compared to delayed larger rewards) in 61 heavy drinkers (62% with an AUD). In addition, based on theoretical accounts that emphasize the role of craving in reward valuation and preferences for immediate rewards, craving for alcohol was also examined in relation to these behavioral economic variables and the alcohol-related variables. Intensity of alcohol demand and delayed reward discounting were significantly associated with AUD symptoms, but not with quantitative measures of alcohol use, and were also moderately correlated with each other. Likewise, craving was significantly associated with AUD symptoms, but not with alcohol use, and was also significantly correlated with both intensity of demand and delayed reward discounting. These findings further emphasize the relevance of behavioral economic indices of motivation to AUDs and the potential importance of craving for alcohol in this relationship.

Sexual assault and alcohol use: exploring the self-medication hypothesis.

Though a link between sexual victimization and alcohol use has been well documented, the mechanisms underlying this relationship remain unclear. The current study used path analysis to examine the role of self-reported levels of psychological distress and the function of alcohol use as indirect pathways between adult sexual assault and alcohol use. Participants were 318 undergraduate female victims and nonvictims of adult sexual assault. Results showed that a history of sexual assault was associated with increased psychological distress, which in turn contributed to alcohol use via negative reinforcement. Taken together, these findings provided support for the hypothesis that women who have been sexually assaulted consume alcohol, in part, to self-medicate. The implications for future research are discussed.

Polymorphisms of the mu-opioid receptor and dopamine D4 receptor genes and subjective responses to alcohol in the natural environment.

Polymorphisms of the mu-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 examined these associations in the natural environment using ecological momentary assessment. 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 5 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., >or=7 tandem repeats) of the DRD4 endorsed greater urge to drink than homozygotes for the short allele. Effects of OPRM1 and DRD4 variable-number-of-tandem-repeats 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.

Enhancing Substance Abuse Treatment Engagement in Incarcerated Adolescents.

The purpose of this study was to determine whether motivational interviewing (MI), compared with an attention control condition (relaxation training [RT]) enhances substance abuse treatment engagement in incarcerated adolescents. At the start of incarceration, adolescents were randomly assigned to individually administered MI or RT. Subsequently, therapists and adolescents (N = 130) rated degree of adolescent participation in the facilitys standard care group-based treatments targeting crime and substance use. All adolescents received the facility standard care treatment after their individual MI or RT session. MI statistically significantly mitigated negative substance abuse treatment engagement. Other indicators of treatment engagement were in the expected direction; however, effect sizes were small and nonsignificant. These findings are significant, given concerns regarding the deleterious effects of treating delinquent adolescents in groups and the potential for adolescents to reinforce each others negative behavior, which in turn may lead to escalated substance use and other delinquent behaviors after release.

Effects of topiramate on urge to drink and the subjective effects of alcohol: a preliminary laboratory study.

BACKGROUND Topiramate was recently reported to be efficacious in reducing drinking rates and craving among individuals with alcohol dependence in a randomized controlled trial, but dose effects could not be determined. This laboratory study systematically examined the dose-dependent effects of topiramate on cue-elicited craving and other putative mechanisms of its pharmacotherapeutic effects on drinking. METHODS Male and female heavy drinkers (n = 61) were randomized to 1 of 3 medication conditions (200 mg/d; 300 mg/d; placebo) in a double-blind study. Participants reached the target dose after a 32-day titration period, then were stabilized for approximately 1 week. All then participated in a laboratory assessment of alcohol cue reactivity and of the subjective effects of a moderate dose of alcohol. RESULTS Both doses of topiramate reduced the frequency of heavy drinking during the titration period as compared to placebo. However, topiramate did not affect self-reported craving for alcohol during the titration period, during the cue reactivity protocol, or in response to the alcohol challenge procedure. Topiramate reduced the stimulating effects of alcohol ingestion compared to placebo, but only in the 200 mg group. CONCLUSIONS The results of this study support previous findings that topiramate reduces drinking, but the behavioral mechanism underlying this effect does not appear to be attenuation of craving for alcohol as measured using the approaches employed in this study. Rather, the results tentatively suggest that topiramate may exert its beneficial effects by altering the subjective experiences of alcohol consumption. Limitations of the current study are discussed and complementary methods are recommended for future studies, such as the use of behavioral economic paradigms and ecological momentary assessment.

Initial evidence of an association between OPRM1 and adolescent alcohol misuse.

BACKGROUND Considerable research efforts have attempted to identify genes associated with alcoholism among adults, yet few studies have examined adolescents. Identifying genes associated with alcohol misuse in youth is important given that the relative contribution of genetic and environmental influences on alcoholism varies across development. The purpose of this study was to examine the association between a polymorphism of the mu-opioid receptor gene (OPRM1) and alcohol misuse in a sample of youth and to test whether heightened sensitivity to the reinforcing effects of alcohol mediated this relationship. METHODS Adolescents (n = 187; mean age = 15.4 years; 47.6% female) were genotyped for A118G (rs1799971), a single-nucleotide polymorphism (SNP) of the OPRM1 gene, and assessed for alcohol use disorder (AUD) diagnoses and other psychopathology. Alcohol misuse was also measured continuously to maximize detection of drinking problems in youth. Drinking motives were used to capture the extent to which youth consumed alcohol to enhance positive affect. RESULTS AUD groups differed significantly in terms of allelic distributions of the A118G SNP, such that 51.9% of youth with an AUD carried at least one copy of the G allele compared to 16.3% of non-AUD controls. Those who carried the G allele endorsed drinking to enhance positive affect more strongly than those who were homozygous for the A allele and drinking to enhance positive affect mediated the association between OPRM1 and alcohol-related problems. CONCLUSIONS These data build on findings from adult studies and provide the first evidence that a polymorphism of the OPRM1 receptor gene is associated with the development of early-onset alcohol-related problems during adolescence, in part, by heightening sensitivity to the reinforcing effects of alcohol.

Influence of antisocial and psychopathic traits on decision-making biases in alcoholics.

BACKGROUND Although decision-making processes have become a principal target of study among addiction researchers, few studies have specifically examined decision-making among individuals with alcohol dependence (AD) and findings to date are mixed. The present study examined the relationship between AD and decision-making, and tested whether different facets of antisocial and psychopathic traits explain this association. METHODS Participants were men with AD (n = 22), AD and comorbid antisocial personality disorder (AD + ASPD; n = 17), or a history of recreational alcohol use, but no current or lifetime symptoms of a substance use disorder, conduct disorder, or ASPD (n = 21). Decision-making was tested using the Iowa Gambling Task (IGT). RESULTS Across groups, participants reported similar levels of awareness of the contingencies of the task, but the AD groups with and without ASPD had poorer IGT performance compared with controls (p < 0.05). A block-by-block analysis revealed that while AD had slow but steady improvement across the task, AD + ASPD exhibited initial improvement followed by a significant decrease in advantageous decision-making during the last 20 trials (p < 0.05). This was further confirmed via evidence that impulsive/antisocial personality traits but not psychopathic traits mediated poor IGT performance beyond ASPD diagnosis. CONCLUSIONS Alcohol-dependent males favored risky choices regardless of whether they met criteria for ASPD. However, decision-making deficits were more pronounced among those with ASPD, and personality traits characterized by impulsive and antisocial tendencies mediated the relationship between AD and decision-making.

Effects of naltrexone on adolescent alcohol cue reactivity and sensitivity: an initial randomized trial

Adolescent alcohol use is associated with myriad adverse consequences and contributes to the leading causes of mortality among youth. Despite the magnitude of this public health problem, evidenced‐based treatment initiatives for alcohol use disorders in youth remain inadequate. Identifying promising pharmacological approaches may improve treatment options. Naltrexone is an opiate receptor antagonist that is efficacious for reducing drinking in adults by attenuating craving and the rewarding effects of alcohol. Implications of these findings for adolescents are unclear; however, given that randomized trials of naltrexone with youth are non‐existent. We conducted a randomized, double‐blinded, placebo‐controlled cross‐over study, comparing naltrexone (50 mg/daily) and placebo in 22 adolescent problem drinkers aged 15–19 years (M = 18.36, standard deviation = 0.95; 12 women). The primary outcome measures were alcohol use, subjective responses to alcohol consumption, and alcohol–cue‐elicited craving assessed in the natural environment using ecological momentary assessment methods, and craving and physiological reactivity assessed using standard alcohol cue reactivity procedures. Results showed that naltrexone reduced the likelihood of drinking and heavy drinking (Ps ≤ 0.03), blunted craving in the laboratory and in the natural environment (Ps ≤ 0.04), and altered subjective responses to alcohol consumption (Ps ≤ 0.01). Naltrexone was generally well tolerated by participants. This study provides the first experimentally controlled evidence that naltrexone reduces drinking and craving, and alters subjective responses to alcohol in a sample of adolescent problem drinkers, and suggests larger clinical trials with long‐term follow‐ups are warranted.

Randomized Clinical Trial of Motivational Enhancement of Substance Use Treatment Among Incarcerated Adolescents: Post-Release Condom Non-Use

ABSTRACT Evaluated impact of motivational enhancement (ME) of substance abuse treatment compared to relaxation training (RT) on sex without condoms (overall and involving substance use) 3 months following release among incarcerated adolescents. This randomized clinical trial involved 114 incarcerated adolescents from the Northeast. Regression analyses determined if treatment condition, baseline levels of depressive symptoms, and their interaction predicted condom non-use 3 months post-release, controlling for baseline condom non-use. Among those who reported fewer baseline depressive symptoms, those in ME condition reported significantly less condom non-use, in general and involving marijuana use compared with those in RT condition. Periods of incarceration represent opportunities to help juvenile detainees reduce behaviors that impact their health and the health of those with whom they interact in the Community.