Rare coding variants in CHRNB2 reduce the likelihood of smoking.

Human genetic studies of smoking behavior have been thus far largely limited to common variants. Studying rare coding variants has the potential to identify drug targets. We performed an exome-wide association study of smoking phenotypes in up to 749,459 individuals and discovered a protective association in CHRNB2, encoding the ß2 subunit of the α4ß2 nicotine acetylcholine receptor. Rare predicted loss-of-function and likely deleterious missense variants in CHRNB2 in aggregate were associated with a 35% decreased odds for smoking heavily (odds ratio (OR) = 0.65, confidence interval (CI) = 0.56-0.76, P = 1.9 × 10-8). An independent common variant association in the protective direction ( rs2072659 ; OR = 0.96; CI = 0.94-0.98; P = 5.3 × 10-6) was also evident, suggesting an allelic series. Our findings in humans align with decades-old experimental observations in mice that ß2 loss abolishes nicotine-mediated neuronal responses and attenuates nicotine self-administration. Our genetic discovery will inspire future drug designs targeting CHRNB2 in the brain for the treatment of nicotine addiction.

Genetic diversity fuels gene discovery for tobacco and alcohol use.

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1-4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.

Effects of genetic risk for alcohol dependence and onset of regular drinking on the progression to alcohol dependence: A polygenic risk score approach.

BACKGROUND: Prior studies have established the importance of genetic contributions to the etiology of alcohol dependence (AD), and suggested an early onset of alcohol use represents an initial marker of this genetic risk, which is associated with a more rapid progression to AD and increased risk for AD itself. Building on prior work, the current study examined whether the additive effects of AD risk variants predicted the rate of progression to AD from the onset of regular drinking, a drinking milestone with high clinical relevance to AD prevention. METHODS: Data from 1501 European-ancestry adults from the University of California - San Francisco Family Alcoholism Study were used to examine whether polygenic risk scores for AD (PRSAD) and age-at-onset of regular drinking contributed uniquely to the likelihood of having a lifetime AD diagnosis and the rate of progression from regular drinking to AD. Mixed effects logistic regression and Cox proportional hazards regression analyses were employed. RESULTS: Increases in PRSAD were associated with a faster progression from regular drinking to AD independent of age-at-onset of regular drinking. An independent effect of age-at-onset of regular drinking was also observed indicating that a one-year delay in regular drinking was associated with a 7% decrease in the hazard of progression to AD among drinkers with an early onset (≤ 18), but a 3% increase among drinkers with a late onset (> 18) of regular drinking. CONCLUSIONS: These results broaden our understanding of the contributions of measured genotypes underlying AD-risk on the etiology and clinical course of AD.

Genetic architecture of four smoking behaviors using partitioned SNP heritability.

BACKGROUND AND AIMS: Although genome-wide association studies have identified many loci that influence smoking behaviors, much of the genetic variance remains unexplained. We characterized the genetic architecture of four smoking behaviors using single nucleotide polymorphism (SNP) heritability (h2SNP ). This is an estimate of narrow-sense heritability specifically estimating the proportion of phenotypic variation due to causal variants (CVs) tagged by SNPs. DESIGN: Partitioned h2SNP analysis of smoking behavior traits. SETTING: UK Biobank. PARTICIPANTS: UK Biobank participants of European ancestry. The number of participants varied depending on the trait, from 54 792 to 323 068. MEASUREMENTS: Smoking initiation, age of initiation, cigarettes per day (CPD; count, log-transformed, binned and dichotomized into heavy versus light) and smoking cessation with imputed genome-wide SNPs. FINDINGS: We estimated that, in aggregate, approximately 18% of the phenotypic variance in smoking initiation was captured by imputed SNPs [h2SNP = 0.18, standard error (SE) = 0.01] and 12% [SE = 0.02] for smoking cessation, both of which were more than twice the previously reported estimates. Estimated age of initiation (h2SNP  = 0.05, SE = 0.01) and binned CPD (h2SNP  = 0.1, SE = 0.01) were substantially below published twin-based h2 of 50%. CPD encoding influenced estimates, with dichotomized CPD h2SNP  = 0.28. There was no evidence of dominance genetic variance for any trait. CONCLUSION: A biobank study of smoking behavior traits suggested that the phenotypic variance explained by SNPs of smoking initiation, age of initiation, cigarettes per day and smoking cessation is modest overall.

Effects of Common and Rare Chromosome 4 GABAergic Gene Variation on Alcohol Use and Antisocial Behavior.

OBJECTIVE: Epidemiological estimates suggest that nearly half of individuals diagnosed with alcohol use disorder will be diagnosed with another mental health disorder, with strong associations involving other externalizing disorders. Molecular genetic studies investigating the relation between alcohol use disorder and externalizing behaviors (e.g., antisocial behavior) have focused on a cluster of chromosome 4 γ-aminobutyric acid (GABA) receptor genes (GABRG1-A2-A4-B1) but have generated varying results. METHOD: The current study examined associations between common and rare variation in this region with alcohol use disorder and antisocial behavior using genetic sequencing data. Specifically, the University of California at San Francisco Family Alcoholism Sample (n = 1,610; 62% female) was used to conduct common and rare variant association tests in the GABRG1-A2-A4-B1 cluster with DSM-5 alcohol use disorder symptom counts, antisocial behavior, and a product term representing their interaction. RESULTS: Gene-based analyses of rare variation resulted in a significant association between rare GABRA2 variation and the interaction term. Single-variant analysis yielded only nominally significant associations. The strongest association for alcohol use disorder (rs3756007) was located in GABRA2, the strongest association for antisocial behavior (rs11941860) was located in GABRG1, and the interaction term yielded top associations in GABRA2 (rs2119183) and the intergenic region between GABRA2 and GABRG1 (rs536599). Common and rare variant associations for the interaction remained similar when covarying for the effects of the other type of variation, suggesting that the significant rare variant signal is independent of common variant contributions. CONCLUSIONS: The present study suggests that both rare and common variant associations in GABRA2 confer risk for alcohol use disorder and antisocial behaviors, indicating a potential liability toward externalizing behavior more broadly.

Polygenic liability for schizophrenia predicts shifting-specific executive function deficits and tobacco use in a moderate drinking community sample.

Individuals with schizophrenia have higher lifetime rates of substance use disorders than the general population, and research suggests high comorbidity rates may be partially explained by shared genetic influences related to common underlying etiology. Moreover, deficits in executive functions are thought to be central to the diagnosis of schizophrenia and are likewise associated with alcohol and tobacco use. The current study examined the associations between schizophrenia polygenic risk scores and tobacco and alcohol use and the mediation of these associations by executive function sub-domains. Results from the Psychiatric Genomics Consortium's meta-analysis of genome-wide association studies of schizophrenia were used to calculate polygenic risk scores in a sample of moderate drinkers. Schizophrenia risk scores were significantly associated with shifting-specific executive function deficits and tobacco use phenotypes. However, risk scores were not significantly associated with alcohol use and executive functions were not significantly associated with either tobacco or alcohol use. These findings extend previous research by suggesting that genetic risk for schizophrenia may be associated with specific sub-domains of executive function as well as smoking. The lack of a relation with alcohol use suggests genetic factors related to schizophrenia and executive functioning may not influence drinking in a non-disordered, social-drinking sample.

Genetic variation in the exome: Associations with alcohol and tobacco co-use.

Shared genetic factors represent one underlying mechanism thought to contribute to high rates of alcohol and tobacco co-use and dependence. Common variants identified by molecular genetic studies tend to confer only small disease risk, and rare protein-coding variants are posited to contribute to disease risk, as well. However, given that genotyping technologies allowing for their inclusion in association studies have only recently become available, the magnitude of their contribution is poorly understood. The current study examined genetic variation in protein-coding regions (i.e., the exome) for associations with measures of lifetime alcohol and tobacco co-use. Participants from the UCSF Family Alcoholism Study (N = 1,862) were genotyped using an exome-focused genotyping array, and assessed for DSM-IV diagnoses of alcohol and tobacco dependence and quantitative consumption measures using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism. Analyses included single variant, gene-based, and pathway-based tests of association. One EMR3 variant and a pathway related to genes upregulated in mesenchymal stem cells during the late phase of adipogenesis met criteria for statistical significance. Suggestive associations were consistent with previous findings from studies of substance use and dependence, including variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster with cigarettes smoked per day. Further, several variants and genes demonstrated suggestive association across phenotypes, suggesting that shared genetic factors may underlie risk for increased levels of alcohol and tobacco use, as well as psychopathology more broadly, providing insight into our understanding of the genetic architecture underlying these traits. (PsycINFO Database Record

A cis-eQTL in OPRM1 is Associated with Subjective Response to Alcohol and Alcohol Use.

BACKGROUND: A functional polymorphism within the µ-opioid receptor (OPRM1) gene, rs1799971 (A118G), previously has been associated with measures of alcohol use and sensitivity to its effects, but findings have been inconclusive. A recent study suggested that a second nearby variant within OPRM1, rs3778150, is robustly associated with heroin dependence and fully explained a smaller observed association with rs1799971. Given evidence that the rs3778150-C allele is associated with decreased OPRM1 expression levels in the human brain, the current study sought to test the hypothesis that rs3778150 represents a causal variant within OPRM1 that increases risk for a variety of alcohol use phenotypes. METHODS: Participants with genotype and phenotype data from a larger experimental study (N = 152) were assessed on measures of subjective response to alcohol and alcohol use. Measures included (i) the Self-Rating of the Effects of Alcohol and the Alcohol Sensitivity Questionnaire, (ii) the Biphasic Alcohol Effects Scale (BAES) and ratings of subjective intoxication, and (iii) average number of drinks per week in the past month. RESULTS: Compared to rs3778150-T homozygous individuals, carriers of the rs3778150-C allele exhibited significantly lower retrospective self-report levels of alcohol sensitivity. Carriers of the rs3778150-C allele also exhibited lower levels of BAES alcohol-related stimulation during an alcohol challenge and reported higher levels of drinking in the last 30 days. With the exception of lower levels of BAES alcohol-related sedation, the rs1799971 variant did not show consistent significant association with any of the alcohol phenotypes in the presence of rs3778150. CONCLUSIONS: Results suggest that rs3778150 may be causally related to alcohol use phenotypes, and could potentially account for previously observed associations of rs1799971 with substance use phenotypes. Future studies may investigate potential causal relations among genetic variants in OPRM1, subjective response to alcohol, and drinking phenotypes to further delineate the effects of rs3778150.

A Novel Tobacco Use Phenotype Suggests the 15q25 and 19q13 Loci May be Differentially Associated With Cigarettes per Day and Tobacco-Related Problems.

INTRODUCTION: Tobacco use is associated with variation at the 15q25 gene cluster and the cytochrome P450 (CYP) genes CYP2A6 and CYP2B6. Despite the variety of outcomes associated with these genes, few studies have adopted a data-driven approach to defining tobacco use phenotypes for genetic association analyses. We used factor analysis to generate a tobacco use measure, explored its incremental validity over a simple indicator of tobacco involvement: cigarettes per day (CPD), and tested both phenotypes in a genetic association study. METHODS: Data were from the University of California, San Francisco Family Alcoholism Study (n = 1942) and a Native American sample (n = 255). Factor analyses employed a broad array of tobacco use variables to establish the candidate phenotype. Subsequently, we conducted tests for association with variants in the nicotinic acetylcholine receptor and CYP genes. We explored associations with CPD and our measure. We then examined whether the variants most strongly associated with our measure remained associated after controlling for CPD. RESULTS: Analyses identified one factor that captured tobacco-related problems. Variants at 15q25 were significantly associated with CPD after multiple testing correction (rs938682: p = .00002, rs1051730: p = .0003, rs16969968: p = .0003). No significant associations were obtained with the tobacco use phenotype; however, suggestive associations were observed for variants in CYP2B6 near CYP2A6 (rs45482602: ps = .0082, .0075) and CYP4Z2P (rs10749865: ps = .0098, .0079). CONCLUSIONS: CPD captures variation at 15q25. Although strong conclusions cannot be drawn, these finding suggest measuring additional dimensions of problems may detect genetic variation not accounted for by smoking quantity. Replication in independent samples will help further refine phenotype definition efforts. IMPLICATIONS: Different facets of tobacco-related problems may index unique genetic risk. CPD, a simple measure of tobacco consumption, is associated with variants at the 15q25 gene cluster. Additional dimensions of tobacco problems may help to capture variation at 19q13. Results demonstrate the utility of adopting a data-driven approach to defining phenotypes for genetic association studies of tobacco involvement and provide results that can inform replication efforts.

Polygenic risk scores for cigarettes smoked per day do not generalize to a Native American population.

BACKGROUND: Recent studies have demonstrated the utility of polygenic risk scores (PRSs) for exploring the genetic etiology of psychiatric phenotypes and the genetic correlations between them. To date, these studies have been conducted almost exclusively using participants of European ancestry, and thus, there is a need for similar studies conducted in other ancestral populations. However, given that the predictive ability of PRSs are sensitive to differences in linkage disequilibrium (LD) patterns and minor allele frequencies across discovery and target samples, the applicability of PRSs developed in European ancestry samples to other ancestral populations has yet to be determined. Therefore, the current study derived PRSs for cigarettes per day (CPD) from predominantly European-ancestry samples and examined their ability to predict nicotine dependence (ND) in a Native American (NA) population sample. METHOD: Results from the Tobacco and Genetics Consortium's meta-analysis of genome-wide association studies of CPD were used to compute PRSs in a NA community sample (N=288). These scores were then used to predict ND diagnostic status. RESULTS: The PRS was not significantly associated with liability for ND in the full sample. However, a significant interaction between PRS and percent NA ancestry was observed. Risk scores were positively associated with liability for ND at higher levels of European ancestry, but no association was observed at higher levels of NA ancestry. CONCLUSION: These findings illustrate how differences in patterns of LD across discovery and target samples can reduce the predictive ability of PRSs for complex traits.

Women's unprotected sex intentions: roles of sexual victimization, intoxication, and partner perception.

Sexually victimized women may make sexual decisions differently than nonvictimized women. This study used an eroticized scenario and laboratory alcohol administration to investigate the roles of victimization history, intoxication, and relationship context in women's perceptions of a male partner and their subsequent intentions for unprotected sex. A community sample of 436 women completed childhood sexual abuse (CSA) and adolescent/adult sexual assault (ASA) measures. After random assignment to an alcohol or control condition, participants read and projected themselves into a sexual scenario that depicted the male partner as having high or low potential for a lasting relationship. Participants rated their perceptions of his intoxication, sexually transmitted infection (STI) risk level, and anticipated reactions to insistence on condom use. They then indicated their likelihood of allowing the partner to decide how far to go sexually (abdication) and of engaging in unprotected sex. Structural equation modeling (SEM) analyses revealed that intoxication predicted greater unprotected sex likelihood indirectly via abdication. CSA and ASA predicted partner perceptions, which in turn predicted unprotected sex likelihood. These findings indicate that, compared to their nonvictimized counterparts, sexually victimized women may respond differently in sexual encounters partly as a function of their perceptions of partners' STI risk and anticipated reactions to condom insistence.

Sexual victimization, alcohol intoxication, sexual-emotional responding, and sexual risk in heavy episodic drinking women.

This study used an experimental paradigm to investigate the roles of sexual victimization history and alcohol intoxication in young women's sexual-emotional responding and sexual risk taking. A nonclinical community sample of 436 young women, with both an instance of heavy episodic drinking and some HIV/STI risk exposure in the past year, completed childhood sexual abuse (CSA) and adolescent/adult sexual assault (ASA) measures. A majority of them reported CSA and/or ASA, including rape and attempted rape. After random assignment to a high alcohol dose (.10 %) or control condition, participants read and projected themselves into an eroticized scenario of a sexual encounter involving a new partner. As the story protagonist, each participant rated her positive mood and her sexual arousal, sensation, and desire, and then indicated her likelihood of engaging in unprotected sex. Structural equation modeling analyses revealed that ASA and alcohol were directly associated with heightened risk taking, and alcohol's effects were partially mediated by positive mood and sexual desire. ASA was associated with attenuated sexual-emotional responding and resulted in diminished risk taking via this suppression. These are the first findings indicating that, compared to non-victimized counterparts, sexually victimized women respond differently in alcohol-involved sexual encounters in terms of sexual-emotional responding and risk-taking intentions. Implications include assessing victimization history and drinking among women seeking treatment for either concern, particularly women at risk for HIV, and alerting them to ways their histories and behavior may combine to exacerbate their sexual risks.

The potential of alcohol "heat-of-the-moment" scenarios in HIV prevention: A qualitative study exploring intervention implications.

Scenarios simulating real-world risk situations have proven effective for substance use intervention methods and could potentially prove useful as an HIV-prevention method. This study explored qualitatively the development and use of such "in-the-moment" methods. We interviewed 97 moderate-drinking women (50 % Caucasian) after participation in an experiment requiring that they project themselves into a risky-sex scenario. Most participants (58 %) reported experiencing the scenario as a reflective tool characterized by two primary themes: (1) increased awareness of risk and (2) contemplation of behavior change. Findings suggest that "in-the-moment" methods depicting real-world risk situations and providing opportunities to reflect about behavioral choices and subsequent outcomes could prove a useful adjunct to HIV/AIDS-prevention interventions. Such methods could potentially augment existing prevention protocols.

Association of the ALDH1A1*2 promoter polymorphism with alcohol phenotypes in young adults with or without ALDH2*2.

BACKGROUND: Prior studies suggest a possible association of a promoter polymorphism in the ALDH1A1 gene ( ALDH1A1*2 ) with alcohol use or dependence. The aim of this study was to examine the association of ALDH1A1*2 with drinking behaviors in Asian young adults and to examine ALDH2 genotype as a potential moderator of these associations. METHODS: Asian young adults (n = 951) were recruited from 2 college sites for studies of genetic associations with alcohol use behavior. Participants completed comprehensive background questionnaires on demographics and drinking behavior. Fingertip blood samples were obtained for DNA extraction and analysis. RESULTS: Participants with the ALDH2*1/*2 genotype reported significantly lower levels (frequency and quantity) of drinking within the last 90 days, fewer numbers of heavy drinking episodes within the last 90 days, and lower lifetime maximum consumption levels compared with ALDH2*1/*1 participants. There were no significant main effects of ALDH1A1*2 on any drinking variables, nor was there a significant interaction between ALDH2 and ALDH1A1 genotypes on drinking outcomes. CONCLUSIONS: The association of ALDH2*2 with reduced alcohol consumption replicates previous findings across numerous studies. Although ALDH1A1*2 was not associated with drinking levels, the lack of an ALDH1A1*2 effect in ALDH2*2 individuals is consistent with the only other study that has examined these associations in East Asian populations.

Risky sex: interactions among ethnicity, sexual sensation seeking, sexual inhibition, and sexual excitation.

Rates of sexually transmitted infections, including HIV, vary across ethnic minority groups, yet few studies have evaluated sexual risk behaviors and their psychological correlates to determine if risk and protective factors vary by ethnicity. The purpose of the current study was to assess sexual sensation seeking (SSS), sexual inhibition (SIS1 and SIS2), and sexual excitation (SES) as correlates of risky sexual behaviors in 106 (55 male and 51 female) Asian Americans, African Americans, and Caucasian Americans. Results revealed that higher SSS was associated with more vaginal and anal sex partners. Further, the association between SSS and the number of anal sex partners was positive among Asian Americans and Caucasians, but non-significant among African Americans. SIS1 was positively associated with unprotected sex on the first date among Asian Americans and African Americans. However, the association was not significant for Caucasians. SIS2 was negatively associated with general unprotected sex, and SES was positively associated with the number of vaginal sex partners. Findings suggest that ethnicity plays an important moderating role in the relationship between sexual traits and risky sexual behaviors.

Implicit Coping and Enhancement Motives Predict Unique Variance in Drinking in Asian Americans.

Automatic cognitive processes have been shown to be unique predictors of drinking behavior and can be assessed using implicit measures. Drinking motives (e.g., enhancement and coping motives), which are also predictive of alcohol use, have not been studied using implicit measures. Moreover, in the U.S., implicit measures have been studied in samples largely consisting of Caucasian or White Americans. This study adapted the Implicit Association Test (IAT) to examine automatic analogues of enhancement and coping drinking motives and approach/avoid tendencies in 56 Asian-American undergraduates. Enhancement and coping IATs were correlated with self-reported drinking motives and predicted unique variance in drinking frequency and heavy drinking when controlling for self-reported motives. Approach IAT scores were neither associated with self-reported approach/avoid tendencies nor predictive of drinking behaviors. These findings provide initial support for the unique predictive utility of drinking motives in Asian Americans, an understudied population.

Evaluating a cognitive model of ALDH2 and drinking behavior.

BACKGROUND: Despite evidence for genetic influences on alcohol use and alcohol-related cognitions, genetic factors and endophenotypes are rarely incorporated in cognitive models of drinking behavior. This study evaluated a model of ALDH2 and drinking behavior stipulating cognitive factors and alcohol sensitivity as accounting for genetic influences on drinking outcomes. METHODS: Participants were Asian-American young adults (n = 171) who completed measures of alcohol cognitions (drinking motives, drinking refusal self-efficacy, and alcohol expectancies), alcohol sensitivity, drinking behavior, and alcohol-related problems as part of a prospective study. Structural equation modeling (SEM) evaluated a model of drinking behavior that stipulated indirect effects of ALDH2 on drinking outcomes through cognitive variables and alcohol sensitivity. RESULTS: The full model provided an adequate fit to the observed data, with the measurement model explaining 63% of the variance in baseline heavy drinking and 50% of the variance in alcohol-related problems at follow-up. Associations of ALDH2 with cognitive factors and alcohol sensitivity were significant, whereas the association of ALDH2 with drinking was not significant with these factors included in the model. Mediation tests indicated significant indirect effects of ALDH2 through drinking motives, drinking refusal self-efficacy, and alcohol sensitivity. CONCLUSIONS: Results are consistent with the perspective that genetic influences on drinking behavior can be partly explained by learning mechanisms and implicate cognitive factors as important for characterizing associations of ALDH2 with drinking.

Evaluation of a brief web-based genetic feedback intervention for reducing alcohol-related health risks associated with ALDH2.

There is increasing interest in health interventions that incorporate genetic risk information. Although genetic feedback has been evaluated as an adjunct to smoking cessation interventions, its efficacy for reducing alcohol-related risks is unknown. The purpose of this study was to evaluate the feasibility, acceptability, and efficacy of a web-based alcohol intervention incorporating genetic feedback and risk information specific to ALDH2 genotype. The ALDH2*2 variant is associated with partial protection against alcohol dependence but confers significantly increased risk for alcohol-related cancers as a function of alcohol exposure. Two hundred Asian-American young adults were randomly assigned to receive web-based personalized genetic feedback or attention-control feedback. Genetic feedback included health risk information specific to alcohol-related cancer or alcohol dependence, depending on genotype. Outcomes included postintervention drinking behavior and theoretical correlates of behavior change. Genetic feedback and risk information resulted in significant reductions in 30-day drinking frequency and quantity among participants with the ALDH2*1/*2 genotype. Genetic feedback was rated highly by participants and also showed some effects on theoretical correlates of behavior change. Results provide initial evidence of the feasibility, acceptability, and brief efficacy of web-based genetic feedback for reducing alcohol-related health risks associated with ALDH2 genotype.

Assessing women's sexual arousal in the context of sexual assault history and acute alcohol intoxication.

INTRODUCTION: Few studies have examined differences in women's sexual arousal based on sexual assault history (SAH) or in-the-moment alcohol intoxication. Only one has examined combined effects. Findings regarding the relationship between SAH and arousal are contradictory. AIM: We aimed to determine the relationship between SAH, alcohol intoxication, and sexual arousal. METHODS: Women were randomly assigned to an alcohol (target blood alcohol level = 0.10%) or control condition and categorized as having an SAH or not. After beverage administration, all women watched erotic films while genital arousal (vaginal pulse amplitude; VPA) was measured. Afterward, self-reported sexual arousal was measured. MAIN OUTCOME MEASURES: Genital response was measured by VPA using vaginal photoplethysmography while watching erotic films. Self-reported sexual arousal was assessed after watching erotic films. RESULTS: Women with an SAH had smaller increases in genital arousal in response to the films than women without an SAH. Intoxicated women had smaller increases in genital arousal than sober women. However, no differences for SAH or intoxication were found in self-reported arousal. CONCLUSION: SAH and alcohol intoxication are associated with smaller increases in genital arousal compared to women without an SAH and sober women, suggesting that these co-occurring factors impact sexual arousal.

Language-based measures of mindfulness: initial validity and clinical utility.

This study examined relationships among language use, mindfulness, and substance-use treatment outcomes in the context of an efficacy trial of mindfulness-based relapse prevention (MBRP) for adults with alcohol and other drug use (AOD) disorders. An expert panel generated two categories of mindfulness language (ML) describing the mindfulness state and the more encompassing "mindfulness journey," which included words describing challenges of developing a mindfulness practice. MBRP participants (n = 48) completed baseline sociodemographic and AOD measures, and participated in the 8-week MBRP program. AOD data were collected during the 4-month follow-up. A word count program assessed the frequency of ML and other linguistic markers in participants' responses to open-ended questions about their postintervention impressions of mindfulness practice and MBRP. Findings supported concurrent validity of ML categories: ML words appeared more frequently in the MBRP manual compared to the 12-step Big Book. Further, ML categories correlated with other linguistic variables related to the mindfulness construct. Finally, predictive validity was supported: greater use of ML predicted fewer AOD use days during the 4-month follow-up. This study provided initial support for ML as a valid, clinically useful mindfulness measure. If future studies replicate these findings, ML could be used in conjunction with self-report to provide a more complete picture of the mindfulness experience.