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)     

Cocaine use can increase cigarette smoking: Evidence from laboratory and naturalistic settings.

Two studies examined the effects of cocaine use on cigarette smoking. Study 1 was conducted with 10 healthy volunteers under controlled laboratory conditions. Participants received double-blind doses of intranasal cocaine HCI (100 mg) or placebo in separate sessions, with each being followed by a 3-hr period of monitored cigarette smoking. Latency to the first cigarette and the mean interval between cigarettes was significantly shorter and the total number of cigarettes smoked was greater after cocaine than placebo administration. Study 2 was conducted by using urine specimens from 9 ambulatory cocaine-dependent patients. Urine cotinine (nicotine metabolite) levels on days when urinalysis testing indicated recent cocaine use were compared with levels on days when urinalysis testing indicated no recent use. Cotinine levels were significantly higher on cocaine-positive days, indicating that cocaine use was associated with greater cigarette smoking. Overall results provide evidence that acute cocaine administration can increase cigarette smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Seeker—Autonomous Long‐range Rover Navigation for Remote Exploration

Under the umbrella of the European Space Agency (ESA) StarTiger program, a rapid prototyping study called Seeker was initiated. A range of partners from space and nonspace sectors were brought together to develop a prototype Mars rover system capable of autonomously exploring several kilometers of highly representative Mars terrain over a three‐day period. This paper reports on our approach and the final field trials that took place in the Atacama Desert, Chile. Long‐range navigation and the associated remote rover field trials are a new departure for ESA, and this activity therefore represents a novel initiative in this area. The primary focus was to determine if current computer vision and artificial intelligence based software could enable such a capability on Mars, given the current limit of around 200 m per Martian day. The paper does not seek to introduce new theoretical techniques or compare various approaches, but it offers a unique perspective on their behavior in a highly representative environment. The final system autonomously navigated 5.05 km in highly representative terrain during one day. This work is part of a wider effort to achieve a step change in autonomous capability for future Mars/lunar exploration rover platforms.     

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)     

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

Effects of abstinence on cigarette smoking among outpatients with schizophrenia.

The authors of this study examined the effects of brief smoking abstinence on smoking among 6 individuals with schizophrenia or schizoaffective disorder. Before 6 of 12 experimental sessions, participants were required to provide breath carbon monoxide (CO) samples indicative of smoking abstinence; before the remaining sessions, participants provided CO samples indicating no abstinence. During sessions, participants obtained smoking opportunities (2 puffs/opportunity) under either fixed ratio-1 or progressive ratio (PR) schedules of reinforcement. Abstinence increased smoking under both schedules and increased breakpoint for smoking under the PR schedule. These data offer further evidence that smoking by individuals with schizophrenia is orderly, operant behavior that is modulated, at least in part, by variables that also affect smoking in people without major mental illness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Subjective and physiological responses to smoking cues in smokers with schizophrenia.

The prevalence of smoking is high among people with schizophrenia. Although several research groups are developing smoking treatments for these smokers, abstinence rates to date have been modest. Methodological tools such as cue exposure are useful in clinical research with smokers in general, but the value of these paradigms with smokers with schizophrenia has yet to be established. The aim of the present study was to determine the subjective and physiological effects of exposure to in vivo smoking cues in smokers with schizophrenia. A total of 25 heavy smokers with schizophrenia or schizoaffective disorder were assessed while nonabstinent and after 2-hr smoking abstinence. Urge to smoke, mood, nicotine withdrawal symptoms, heart rate, and blood pressure were measured during a precue relaxation period, after exposure to neutral cues, and after exposure to smoking cues. Results indicate that both exposure to smoking cues and brief abstinence increased urge levels, nicotine withdrawal symptom levels, and negative affect. Abstinence did not amplify the effects of cues on urges or other cue reactivity measures. These results indicate that smoking cue reactivity laboratory models may be useful for investigating potential smoking treatments for, or neurobiological contributions to, smoking behavior in smokers with schizophrenia.     

Contingent monetary reinforcement of smoking reductions, with and without transdermal nicotine, in outpatients with schizophrenia.

This study was conducted to examine the effects of contingent monetary reinforcement (CM) for smoking reduction, with and without transdermal nicotine, on cigarette smoking in individuals with schizophrenia. Fourteen outpatients participated in each of 3 conditions: (a) CM combined with 21 mg transdermal nicotine, (b) CM combined with placebo patch, and (c) noncontingent reinforcement combined with placebo patch. Each condition lasted 5 days. Carbon monoxide levels were measured 3 times daily, and nicotine withdrawal symptoms were measured once daily in each condition. Results indicated that CM reduced smoking but that 21 mg transdermal nicotine did not enhance that effect. These results offer further evidence supporting the efficacy of CM for reducing smoking among people with schizophrenia, but higher doses of nicotine replacement therapy, or another pharmacotherapy, may be needed to enhance that effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olanzapine reduces urge to smoke and nicotine withdrawal symptoms in community smokers.

Olanzapine (OLAN), an atypical antipsychotic medication with mixed 5-HT2/DA antagonist properties, was predicted to dose-dependently decrease urge to smoke, withdrawal, and cigarette reinforcement in smokers without psychosis. A double-blind placebo-controlled within-subjects cross-over trial investigated the acute effects of OLAN (0, 2.5, and 5.0 mg; counterbalanced order) in 24 community smokers who underwent 10-hr smoking deprivation. Urge to smoke, tobacco withdrawal, and cigarette reinforcement were assessed with cue reactivity and behavioral choice procedures. OLAN (2.5 mg) reduced withdrawal symptoms before and during cue exposure and decreased urge associated with anticipated positive affect from smoking before and during cue exposure; 5.0 mg OLAN decreased withdrawal only when cues were included. OLAN did not affect preference for cigarette puffs versus money, smoke intake, or urge to smoke associated with negative affect relief. The results indicate a potentially beneficial effect of 2.5 mg OLAN on tobacco withdrawal and urge to smoke. Combined 5HT/DA antagonists should be considered for future development of pharmacotherapies for smoking cessation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of smoking abstinence, smoking cues and nicotine replacement in smokers with schizophrenia and controls.

The mechanisms underlying the low smoking cessation rates among smokers with schizophrenia (SS) are unknown. In this laboratory study, we compared the responses of 21 SS and 21 non-psychiatric controls (CS) to manipulations of 5-hour smoking abstinence, transdermal nicotine replacement (0 mg, 21 mg and 42 mg), and in vivo smoking cues. Results indicate that SS were more sensitive than CS to the effects of acute abstinence on carbon monoxide (CO) boost, but not more sensitive to the effects of abstinence on urge levels or withdrawal symptoms. SS and CS did not differ in urge response to in vivo smoking cues, but SS were less consistent in their reactions. These findings suggest that heightened sensitivity to the effects of abstinence on smoke intake may partially account for the low cessation rates experienced by SS, but other potential mechanisms should be explored using behavioral laboratory models.