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 3 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 women and 32 men), 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 with placebo-treated individuals for side effects at target dose. Analyses revealed that an 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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reliability and validity of a demand curve measure of alcohol reinforcement.

Recent clinical research suggests that several self-report behavioral economic measures of relative reinforcing efficacy (RRE) may show utility as indices of substance abuse problem severity. The goal of the present study was to evaluate the reliability and validity of the Alcohol Purchase Task (APT), a RRE measure that uses hypothetical choices regarding alcohol purchases at varying prices (demand curves) to generate several indices of alcohol-related reinforcement. Participants were 38 college students who reported recent alcohol consumption. Both the raw alcohol purchase/consumption values and several of the computed reinforcement parameters (intensity & Omax) showed good to excellent 2-week test–retest reliability. Reinforcement parameters derived from both a linear-elasticity (Hursh, Raslear, Bauman, & Black, 1989) and an exponential (Hursh & Silberberg, 2008) demand curve equation were generally less reliable, despite the fact that both equations provided a good fit to participants’ reported consumption data. The APT measures of demand intensity (number of drinks consumed when price = 0), Omax (maximum expenditure), and elasticity (α) were correlated with weekly drinking, alcohol-related problems, and other self-report RRE measures (relative discretionary monetary expenditures toward alcohol and/or relative substance-related activity participation and enjoyment). Demand intensity was uniquely associated with problem drinking in a regression model that controlled for weekly consumption. These results provide support for the reliability and validity of the RRE indices generated with the APT. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relative reinforcing efficacy of alcohol among college student drinkers.

The construct of relative reinforcing efficacy (RRE) is central to many laboratory and theoretical models of drug abuse, but it has not been widely measured in applied clinical research contexts. The authors used a simulated alcohol purchase task to measure RRE in a sample of 267 college student drinkers. Participants reported their alcohol consumption across a range of prices, and their responses were well-described by a regression equation that has been used to construct demand curves in drug self-administration studies. Several measures of relative reinforcing efficacy were generated, including breakpoint, intensity of demand, elasticity, Pmax (price at which response output is maximized), and Omax (maximum alcohol expenditures). Demand for alcohol was inelastic across the initial range of prices but became elastic as price increased. Students who reported recent heavy drinking reported significantly greater intensity of demand, Omax, and breakpoint. These results provide initial support for the validity of the RRE indices generated with the alcohol purchase task. These results also provide empirical support for programs that attempt to reduce alcohol abuse by eliminating low-cost access to alcohol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Polymorphisms of the μ-opioid receptor and dopamine D? receptor genes and subjective responses to alcohol in the natural environment.

Polymorphisms of the μ-opioid receptor (OPRM1) and dopamine D? 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., ≥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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)