Differences In Subjective Responses Research Articles

Bayesian Semi- and Non-parametric Models for Longitudinal Data with Multiple Membership Effects in R.

We introduce growcurves for R that performs analysis of repeated measures multiple membership (MM) data. This data structure arises in studies under which an intervention is delivered to each subject through the subject's participation in a set of multiple elements that characterize the intervention. In our motivating study design under which subjects receive a group cognitive behavioral therapy (CBT) treatment, an element is a group CBT session and each subject attends multiple sessions that, together, comprise the treatment. The sets of elements, or group CBT sessions, attended by subjects will partly overlap with some of those from other subjects to induce a dependence in their responses. The growcurves package offers two alternative sets of hierarchical models: 1. Separate terms are specified for multivariate subject and MM element random effects, where the subject effects are modeled under a Dirichlet process prior to produce a semi-parametric construction; 2. A single term is employed to model joint subject-by-MM effects. A fully non-parametric dependent Dirichlet process formulation allows exploration of differences in subject responses across different MM elements. This model allows for borrowing information among subjects who express similar longitudinal trajectories for flexible estimation. growcurves deploys "estimation" functions to perform posterior sampling under a suite of prior options. An accompanying set of "plot" functions allow the user to readily extract by-subject growth curves. The design approach intends to anticipate inferential goals with tools that fully extract information from repeated measures data. Computational efficiency is achieved by performing the sampling for estimation functions using compiled C++.

The Subjective Effects of Alcohol Scale: Development and psychometric evaluation of a novel assessment tool for measuring subjective response to alcohol.

Three decades of research demonstrate that individual differences in subjective response (SR) to acute alcohol effects predict heavy drinking and alcohol-related problems. However, the SR patterns conferring the greatest risk remain under debate. Morean and Corbin (2010) highlighted that extant SR measures commonly have limitations within the following areas: assessment of a comprehensive range of effects, assessment of effects over the complete course of a drinking episode, and/or psychometric validation. Furthermore, the consistent pairing of certain SR measures and theoretical models has made integration of findings difficult. To address these issues, we developed the Subjective Effects of Alcohol Scale (SEAS), a novel, psychometrically sound SR measure for use in alcohol administration studies. Pilot data ensured that the SEAS comprised a comprehensive range of effects that varied in terms of valence and arousal and were perceived as plausible effects of drinking. For validation purposes, the SEAS was included in a 2-site, placebo-controlled, alcohol administration study (N = 215). Exploratory and confirmatory factor analyses identified a 14-item, 4-factor model categorizing effects into affective quadrants (high/low arousal positive; high/low arousal negative). SEAS scores evidenced the following: (a) scalar measurement invariance by limb of the blood alcohol curve (BAC) and beverage condition; (b) good internal consistency; (c) convergence/divergence with extant SR measures, alcohol expectancies, and alcohol use; and (d) concurrent/incremental utility in accounting for alcohol-related outcomes, highlighting the novel high arousal negative and low arousal.

Untreated HIV Infection Is Associated With Higher Blood Alcohol Levels

Alcohol abuse has been associated with HIV/AIDS progression, but the effects of HIV infection and treatment on alcohol exposure have not been explored to date. This pilot study examines the relationship of untreated HIV infection to blood alcohol concentrations (BAC) relative to BAC after initiation of antiretroviral therapy (ART). Fifteen volunteers with untreated HIV/AIDS participated in 2 sets of alcohol or alcohol placebo administration studies before and after initiation of ART. Oral alcohol (1 g/kg) or alcohol placebo was administered, participants were followed for pharmacokinetics, subjective responses, and cognitive effects over 8 hours. After initial alcohol studies, the ART regimen selected by participant clinicians was instituted. Observed ART dosing took place for at least 2 weeks. Participants then returned for a second set of alcohol/placebo administration studies while on ART. Participants had significantly higher BAC (P < 0.001) before ART than after ART administration. Alcohol area under the curve was significantly higher in untreated HIV disease (P = 0.011) with significantly higher C(max) (P = 0.015) and C(min) (P = 0.05). The elimination rate was not different between pre-ART and post-ART conditions. Despite declines in BAC after ART initiation, no differences in subjective responses were observed with alcohol administration. Untreated HIV infection is associated with risk for higher BAC than that observed after ART. These findings indicate that patients with untreated HIV disease who ingest alcohol are at greater risk for alcohol associated adverse events and toxicities and underscores the need for simultaneous treatment of alcohol use disorders and HIV in patients with co-occurring conditions.

GABRA2 markers moderate the subjective effects of alcohol

Individual differences in subjective responses (SRs) to alcohol are moderated by genetic variants and may be risk factors for the development of alcohol use disorders. Variation in the GABA(A) α2 receptor subunit gene (GABRA2) has been associated with alcohol dependence (AD). Therefore, we examined whether individual differences in SRs, which reflect sensitivity to the effects of alcohol, are associated with variation in GABRA2. Sixty-nine healthy subjects (21-30 years) underwent a laboratory-based within-session cumulative oral alcohol dosing procedure, achieving a mean peak blood alcohol level of 100.4 mg/dl (standard error = 2.5). Subjective assessments were obtained throughout the session, including ascending and descending limbs of the alcohol curve. We genotyped single nucleotide polymorphisms (SNPs) across the chromosome 4 region spanning GABRA2 and analyzed the effect of genotype and haplotypes on subjective responses to alcohol. Population substructure was characterized through the use of ancestry informative markers. Individual SNP analysis demonstrated that carriers of the minor alleles for SNPs rs279858, rs279844, rs279845, rs279826, rs279828 and rs279836 had lower 'Negative' alcohol effects scores than individuals homozygous for the common allele at each SNP (P = 0.0060, P = 0.0035, P = 0.0045, P = 0.0043, P = 0.0037 and P = 0.0061, respectively). Haplotype effects of block 1 showed concordant results with SNPs in this block (P = 0.0492 and P = 0.0150 for haplotypes 1 and 4, respectively). The minor alleles for several of these SNPs have previously been associated with AD. Our findings provide further evidence that variation within GABRA2 is associated with attenuated negative responses to alcohol, a known risk factor for vulnerability to alcohol use disorders.

Preliminary Evidence for cue-induced Alcohol Craving Modulated by Serotonin Transporter Gene Polymorphism rs1042173

We previously have shown that cue-induced alcohol craving and propensity for higher drinking are modulated by allelic differences in SLC6A4 associated with serotonin transporter (5-HTT) expression level alterations. In an independent study, we characterized another polymorphism, SNP rs1042173, in 3′-untranslated region (3′-UTR) of the same gene, which also altered 5-HTT expression levels; the T allele of rs1042173 was associated with lower mRNA and protein levels. In subsequent analyses, the TT genotype was found to be associated with higher drinking intensity in alcohol-dependent (AD) individuals of Caucasian descent. Building upon these findings, we hypothesized that the low-expressing TT genotype associated with intense drinking would predict higher craving for alcohol in AD individuals. In this pilot study, we sought to test our hypothesis by examining 34 Hispanic AD volunteers (mean age, 34.8 years) for rs1042173 genotype-based [i.e., TT versus TG/GG (Gx)] differences in subjective response to alcohol. We employed a human laboratory paradigm and analyzed the data using a linear mixed-effects model (SAS® PROC MIXED) to assess treatment, cue procedures, and genotype main effects as well as the two-way interaction effects between them. On subjective “urge to drink” and “crave for a drink,” we found a significant main effect of the cue experiment (p ≤ 0.01) and an interaction effect between genotype and cue effects (p < 0.05). TT genotype was associated with higher urge to drink (p = 0.002) and crave for a drink (p = 0.005) when exposed to alcohol cue. Our results not only support the hypothesis that rs1042173 is a genetic marker for cue-induced alcohol craving among AD males but also are suggestive of a neurobiological mechanism associated with the rs1042173-TT genotype that triggers a disproportionate craving in response to alcohol consumption, which in turn may lead to more intense drinking. Future studies with larger sample sizes are needed to characterize the interactive effects of the serotonin transporter-linked polymorphic region (5′-HTTLPR)-L-allele reported in our previous study and of the rs1042173-TT genotype on cue-induced alcohol craving.

Subjective and Neural Responses to Intravenous Alcohol in Young Adults with Light and Heavy Drinking Patterns

Heavy alcohol consumption during young adulthood is a risk factor for the development of serious alcohol use disorders. Research has shown that individual differences in subjective responses to alcohol may affect individuals' vulnerability to developing alcoholism. Studies comparing the subjective and objective response to alcohol between light and heavy drinkers (HDs), however, have yielded inconsistent results, and neural responses to alcohol in these groups have not been characterized. We performed a double-blind, placebo-controlled, randomized crossover alcohol challenge study comparing functional magnetic resonance imaging and subjective response to intravenously administered 6% v/v ethanol to a target blood alcohol concentration of 0.08% or placebo between HDs and social drinkers (SDs). During the imaging, we presented emotional cues in order to measure how emotion modulated the effects of alcohol on the brain's reward circuitry. We found that, at equivalent blood alcohol concentrations, HDs reported lower subjective alcohol effects than SDs. Alcohol significantly activated the nucleus accumbens in SDs, but not in HDs. Self-reported ratings of intoxication correlated with striatal activation, suggesting that activation may reflect subjective experience of intoxication. Fearful faces significantly activated the amygdala in the SDs only, and this activation was attenuated by alcohol. This study shows that HDs not only experience reduced subjective effects of alcohol, but also demonstrate a blunted response to alcohol in the brain's reward system. Our findings indicate that reduced subjective and neural response to alcohol in HDs may be suggestive of either the development of tolerance to alcohol, or of pre-existing decreased sensitivity to alcohol's effects.

Subjective Response to Alcohol Challenge: A Quantitative Review

Individual differences in subjective response to alcohol, as measured by laboratory-based alcohol challenge, have been identified as a candidate phenotypic risk factor for the development of alcohol-use disorders (AUDs). Two models have been developed to explain the role of subjective response to alcohol, but predictions from the 2 models are contradictory, and theoretical consensus is lacking. This investigation used a meta-analytic approach to review the accumulated evidence from alcohol-challenge studies of subjective response as a risk factor. Data from 32 independent samples (total N = 1,314) were aggregated to produce quantitative estimates of the effects of risk-group status (i.e., positive family history of AUDs or heavier alcohol consumption) on subjective response. As predicted by the Low Level of Response Model (LLRM), family history-positive groups experienced reduced overall subjective response relative to family history-negative groups. This effect was most evident among men, with family history-positive men responding more than half a standard deviation less than family history-negative men. In contrast, consistent with the Differentiator Model (DM), heavier drinkers of both genders responded 0.4 standard deviations less on measures of sedation than did the lighter drinkers but nearly half a standard deviation more on measures of stimulation, with the stimulation difference appearing most prominent on the ascending limb of the blood alcohol concentration curve. The accumulated results from 3 decades of family history comparisons provide considerable support for the LLRM. In contrast, results from typical consumption comparisons were largely consistent with predictions of the DM. The LLRM and DM may describe 2 distinct sets of phenotypic risk, with importantly different etiologies and predictions for the development of AUDs.

Gender difference in subjective response to whole-body vibration under standing posture

The aim of this study was to examine whether there exist gender differences in subjective response to whole-body vibration (WBV) under standing posture. Totally twenty-four participants (twelve males and twelve females) rated the discomfort of the test stimuli. The test stimuli included fore-and-aft (x), lateral (y), and vertical (z) vibration of three intensity levels (0.2, 0.4, and 0.8 m/s(2) r.m.s., unweighted), each of which had a constant power spectrum density at frequencies ranging from 1.0 to 20 Hz. The order of the test stimuli was fully randomized, and each stimulus was repeated three times. Subjective scale for discomfort caused by whole-body vibration exposure was obtained for each direction by using the category judgment method. Also, the mean Stevens' power law exponent was obtained for females and males at each vibration direction. The power exponents for females were significantly higher than those for males under fore-and-aft and lateral WBV exposure. Subjective discomfort scales obtained under fore-and-aft and lateral vibration exposure exhibited significant gender differences: the upper limits of categories up to "4: uncomfortable" for females were observed to be higher than those for males while the upper limits of category "5: very uncomfortable" for females were lower than those for males. In contrast, no significant gender differences were observed in the subjective discomfort scale or in the power law exponent for vertical WBV exposure. Our results suggest that females are subjectively more sensitive than males for fore-and-aft and lateral WBV exposure, especially at higher vibration magnitude. Therefore, the differential effects in subjective responses to WBV in females and males should be taken into account in the ISO standard currently used in discomfort evaluation.

P02-334 - Hemodynamic brain response to visual sexual stimuli is different between homosexual and heterosexual men

Many studies showed the differences in subjective response to sexual stimuli between heterosexual and homosexual men. However, the underlying neurobiological factors of sexual orientation are largely unknown. We addressed the question what is the major attribution of the expected differences in brain activation, i.e. neural circuits or different cognitive process. Twenty-eight healthy male volunteers, 14 heterosexuals and 14 homosexuals, were scanned by functional Magnetic Resonance Imaging while subjects were viewing different types of stimuli, i.e. heterosexual couple stimuli (HCS), gay couple stimuli (GCS), lesbian couple stimuli (LCS) and neutral stimuli (NS). SPM02 was used for data analysis. Rating of sexual attractiveness was assessed. Subjective sexual arousal was induced by HCS and GCS in heterosexual and homosexual men, respectively. And sexual disgust was induced by GCS and LCS in heterosexual and homosexual men, respectively. As compared to viewing NS, viewing sexual stimuli induced significant different brain activations most of which had characteristic for cognitive process. These observations suggested that different cognitive pattern was major attribution of different subjective response to sexual stimuli between heterosexual and homosexual men.

Subjective Responses to Alcohol Consumption as Endophenotypes: Advancing Behavioral Genetics in Etiological and Treatment Models of Alcoholism

Individual differences in subjective responses to alcohol consumption represent genetically mediated biobehavioral mechanisms of alcoholism risk (i.e., endophenotype). The objective of this review is three-fold: (1) to provide a critical review the literature on subjective response to alcohol and to discuss the rationale for its conceptualization as an endophenotype for alcoholism; (2) to examine the literature on the neurobiological substrates and associated genetic factors subserving individual differences in subjective response to alcohol; and (3) to discuss the treatment implications of this approach and to propose a framework for conceptualizing, and systematically integrating, endophenotypes into alcoholism treatment.

Subjective Responses to Alcohol Prime Event-Specific Alcohol Consumption and Predict Blackouts and Hangover

Individual differences in subjective response to alcohol and the occurrence of blackouts and hangover are associated with the development of alcohol-use disorders. As such, subjective responses to alcohol, blackouts, and hangover may share a biological vulnerability to excessive alcohol consumption. The purpose of the current study was to examine subjective responses to alcohol as predictors of estimated blood alcohol concentration (BAC), blackouts, and hangover for a single heavy drinking event. Data were collected on 150 (50% female) college students at a large, public university who reported consuming alcohol during their 21st birthday celebration. Using semi-structured interviews and self-report measures, subjective responses to alcohol (at midpoint of a 21 st birthday celebration) were examined as predictors of final estimated BAC, blackouts, and hangover. Stimulant effects reported for the midpoint of the drinking event predicted final estimated BAC. Both stimulant and sedative alcohol effects directly predicted blackouts during the drinking event and the occurrence of a hangover. Neither stimulant nor sedative effects were mediated by final estimated BAC. Retrospective reports of subjective responses to alcohol were associated with the level of intoxication, blackouts, and hangover during a heavy drinking event. Findings therefore suggest the utility of incorporating subjective responses to alcohol into event-specific interventions that are designed to reduce or prevent heavy episodic drinking.

Whites have a more robust hypothalamic–pituitary–adrenal axis response to a psychological stressor than blacks

Differences in the hypothalamic-pituitary-adrenal (HPA) axis response to stress may confer differences in susceptibility to a variety of diseases. We hypothesized that whites would differ from blacks in HPA axis response to a psychological stressor. Healthy subjects aged 18-30 were recruited from Baltimore, Maryland. At initial assessment, they completed psychometric tests measuring anxiety, mood, and personality. Subjects then participated in the Trier Social Stress Test (TSST), which consisted of 10 min of public speaking and mental arithmetic exercises. Subjective anxiety was measured immediately pre- and post-TSST. Race effects on cortisol, adrenocorticotrophin (ACTH), and prolactin responses to the TSST were analyzed by GEE longitudinal analysis methods. The analysis controlled for gender, baseline hormone levels, socioeconomic factors, anxiety, mood, and dimensions of personality. Ninety-eight subjects participated in the TSST. Whites had 36% greater relative mean cortisol response than blacks (95% CI: 10-67%, P=0.004). Whites had significantly higher mean ACTH compared to blacks at 25 min after the start of the TSST (35%, 95% CI: 16-58% greater, P<0.001). There was no difference in prolactin response. Of note, whites and blacks did not differ in subjective anxiety response to the TSST. In sum, we found that whites have a more robust HPA axis response to the TSST compared with blacks, even after controlling for several socioeconomic and psychological factors. In contrast, we observed no difference in prolactin response. There were no differences in subjective response to the TSST to explain the difference in HPA axis response. Further study is indicated to explain this finding and to test whether it can be extrapolated to other forms of stress.

Norepinephrine Transporter Gene Variation Modulates Acute Response to d-Amphetamine

Individual differences in subjective responses to stimulant drugs such as amphetamine may influence risk of abuse as well as clinical-treatment response to these drugs. Because the effects of amphetamine are mediated in part by the norepinephrine transporter (SLC6A2), we examined interindividual differences in mood response to amphetamine in relation to SLC6A2 gene polymorphisms. Ninety-nine healthy volunteers participated in three sessions in which they randomly received either placebo or D-amphetamine (10 mg or 20 mg) under double-blind conditions. Every subject completed self-report measures on subjective effects (Profile of Mood States). Afterward, all individuals were genotyped for eight SLC6A2 gene polymorphisms. Individual genotypes and haplotypes were investigated. The intronic 36001C/C (rs47958) genotype was associated with increases in positive mood and elation after 20 mg of D-amphetamine. Positive mood and elation levels were also found to be associated with the haplotype GCC formed from 28257G/C (rs36017), 28323C/T (rs2270935), and 36001A/C (rs47958). These findings remained significant after adjustment for multiple testing. Polymorphisms in the SLC6A2 gene were associated with mood responses to D-amphetamine. If confirmed, this observation may contribute to a better understanding of interindividual variations in the clinical response to amphetamine and in the risk of becoming addicted to amphetamine.

Preliminary data on the association among the serotonin transporter polymorphism, subjective alcohol experiences, and drinking behavior.

Individual differences in subjective responses to alcohol are believed to have a genetic basis and have been associated with increased risk of alcohol-related problems. There are, however, conflicting results from past studies, perhaps owing to differences in subjective alcohol effects by limb of the blood alcohol curve and the passage of time. The current pilot study evaluated relations among serotonin transporter (SERT) genotype, subjective alcohol responses, and drinking behavior across both the ascending and descending limbs of the blood alcohol curve. Participants (N=222; 68% male) were administered alcohol (target blood alcohol concentration of .06%) with a subsample (n=86) providing genetic data. Following a social stressor, participants were provided the opportunity to engage in ad libitum alcohol consumption. SERT transporter was not significantly associated with ad lib drinking or subjective alcohol effects at individual time points, although a trend toward a SERT by blood alcohol concentration limb interaction was observed for ad lib drinking. In addition, SERT genotype predicted acute tolerance to alcohol effects, with participants homozygous for the long SERT allele developing acute tolerance more rapidly than other genotypes. Although SERT genotype was not reliably associated with ad lib drinking behavior, the results suggest that individuals with the long-long (LL) genotype may develop acute tolerance to alcohol effects more rapidly than heterozygotes or individuals homozygous for the short SERT allele.

Gender differences in subjective responses to hand–arm vibration

There are fewer women than men working in occupations with high exposure to hand–arm vibration. Still there are tens of thousands of women employed in these occupations. The aim of this study was to investigate the gender differences in the subjective experience of hand–arm vibration. Absolute vibrotactile threshold measurements at four frequencies (8, 31.5, 63 and 125 Hz) in 20 participants (10 males, 10 females) were obtained as well as perceived intensity and discomfort ratings of hand–arm vibration made at four intensity levels (0.16, 0.5, 1.6 and 5 m/s 2) for each frequency. No gender differences were found for threshold measurements. However, ratings of both perceived intensity and discomfort were higher for females. Females were significantly more subjectively sensitive than males to stronger physical intensity levels at the higher frequencies. Further, predicted rating values based on ISO frequency weighting underestimated female responses significantly more than male responses to perceived intensity. The results seen here indicate that there should be greater considerations to gender differences in studies of hand–arm vibration. Relevance to industry Results from this study demonstrate differential effects in subjective responses to hand–arm vibration in males and females. This may have implications for ISO frequency weighting currently used in industrial hygiene evaluations.

Subjective intoxication in response to alcohol challenge: heritability and covariation with personality, breath alcohol level, and drinking history.

Numerous studies have identified differences in subjective response to alcohol in subjects differentiated by family history of alcoholism. Results suggest that genetic influences on individual variation in subjective response to alcohol may be a mechanism for genetic effects on alcohol problems. However, direct evidence for genetic effects on subjective response to alcohol is very limited. In a sample of 99 adult twin pairs, we studied genetic influences on subjective intoxication after alcohol challenge. The twins ingested a standard dose of ethanol (0.70 g/kg for men/0.65 g/kg for women), and two measures of subjective response to alcohol were assessed. Genetic effects on variation in subjective intoxication reported 1 hr after drinking were significant and substantial: heritability was 0.60 for a 22-item scale and 0.48 for a brief 2-item measure. Self-report measures of neuroticism, psychasthenia, hostility, and family problems shared significant genetic covariation with subjective intoxication. Achieved breath alcohol level, rate of change in breath alcohol on the descending limb, and individual drinking history all shared familial variation with subjective intoxication. No significant genetic effects for subjective intoxication were found 2 hr after drinking, but familial influences remained present, and many of the same personality, drinking history, and breath alcohol variables were predictive of intoxication. Subjective response to alcohol is heritable, and genetic effects on subjective intoxication are partly shared with genetic effects on personality.

Clinical pharmacology of oral cotinine

Cotinine is the major proximate metabolite of nicotine. The aims of our study were to assess the pharmacokinetics of oral cotinine comparing the use of saliva and plasma concentrations, and to characterize the subjective and cardiovascular effects of oral cotinine in nonsmokers. The clearance and half-life of cotinine measured using plasma or saliva concentrations were similar. There was no change in heart rate or blood pressure, and no differences in subjective response with cotinine compared to placebo. We conclude that administration of oral cotinine with measurement in saliva samples is easy, safe, and provides an accurate estimate of systemic clearance and half-life of cotinine.

Attitudes toward and Perceived Psychosocial Impact of Female Circumcision as Practiced among the Bedouin‐Arabs of the Negev

The present pilot study examines attitudes toward and the perceived psychosocial impact of circumcision as practiced among the Bedouin-Arabs of the Negev, Israel. A convenience sample of 24 women participated in the study: 12 who had experienced the ritual, and 12 who had not, but who had witnessed or been told about the practice of the ritual on women in their extended families. Two research instruments were used: a structured questionnaire, and a semi-structured open-ended interview. Data showed differences in subject responses depending on the research tools. The structured questionnaire revealed that women who had experienced the circumcision gave legitimization and cognitive rationalization to it. In contrast, the semi-structured interview revealed that these same subjects reported insult: traumatization, direct negative influences, and narcissistic insult, and described emotional difficulties during the research interviews. The findings indicated that they had difficulties in mother-daughter relationships and trust. Implications of the ritual on the continuity of polygamy and marital/sexual problems are discussed.

Evaluation of Dyspnea During Physical and Speech Activities in Patients With Pulmonary Diseases

Dyspnea is most commonly assessed by questioning patients about their subjective perception of shortness of breath during physical exertion. Although speech production is altered by pulmonary disease, it has not been included in current dyspnea assessment tools. A questionnaire was developed to address reports of dyspnea during (1) physical activity, (2) speech activity, and (3) simultaneous speech and physical activity. An equal number of self- and experimenter-administered 30-item questionnaires was given to 203 patients with restrictive and obstructive pulmonary diseases. Their responses were analyzed statistically. The questionnaire had high internal consistency for individual items within each of the three sections. The sections were highly correlated but provided separate and distinct information. Factors extracted from each section were related to severity of dyspnea. Pairwise t tests demonstrated highly significant differences in subject responses to the three sections. The least dyspnea was experienced during speech activities, more during physical activities, and the most when speech and physical activities were combined. The questionnaire proved to be a quickly administered tool for providing information about the effect of dyspnea on activities of daily living. Because of the emphasis on dyspnea during speech production, it may be particularly useful for assessing patients who rely extensively on speaking ability for their livelihood.

Smoking and Intoxication after Alcohol Challenge in Women and Men: Genetic Influences

In an earlier analysis, men and women who were current or former smokers were found to report feeling less intoxicated on average than nonsmokers after ingestion of a challenge dose of alcohol. Here, we examine whether differences in subjective response to alcohol and a tendency to smoke cigarettes are transmitted together in families; and, if so, whether this association might be entirely explained by the same heritable factors that influence alcohol intake (as we might expect if both smoking and subjective intoxication are influenced by some general susceptibility for substance use). Alcohol challenge data on 388 Australian male and female twins (194 complete pairs) were reanalyzed using multivariate genetic analysis to evaluate the association between cigarette smoking and self-report intoxication after a standard dose of alcohol. In women, we could not reject the hypothesis of complete genetic overlap between effects on intoxication rating and history of smoking, and a significant residual genetic correlation between smoking and postalcohol intoxication persisted even when genetic influences on alcohol consumption were controlled for. In men, the familial association seemed to be largely environmentally mediated and associated with differences in drinking history. These findings prompt the question of whether, in some individuals, cigarette smoking may contribute to the development of tolerance to the effects of alcohol.