The genetics of alcohol intake and of alcohol dependence

Background: Because alcohol has multiple dose-dependent consequences, it is important to understand the causes of individual variation in the amount of alcohol used. The aims of this study were to assess the long-term repeatability and genetic or environmental causes of variation in alcohol intake and to estimate the degree of overlap with causes of susceptibility to alcohol dependence. Methods: Data were used from three studies conducted between 1980 and 1995 on volunteer adult male and female Australian twin subjects. In each study, alcohol intake was reported both as quantity X frequency and as past-week data. Repeatability was calculated as correlations between occasions and between measures, and the effects of genes and environment were estimated by multivariate model fitting to the twin pair repeated measures of alcohol use. Relationships between mean alcohol use and the lifetime history of DSM-III-R alcohol dependence were tested by bivariate model fitting. Results: Repeatability of the alcohol intake measures was between 0.54 and 0.85, with the highest repeatability between measures within study and the lowest repeatability between the first and last studies. Reported alcohol consumption was mainly affected by genetic factors affecting all times of study and by nonshared environmental factors (including measurement error) unique to each time of study. Genes that affect alcohol intake do affect alcohol dependence, but genetic effects unique to dependence are also significant; environmental effects are largely unique to either intake and dependence. Conclusions: Nearly all the repeatable component of variation in alcohol intake is due to genetic effects. Genes affecting intake also affect dependence risk, but there are other genes that affect dependence alone. Studies aiming to identify genes that affect alcohol use disorders need to test loci and candidate genes against both phenotypes.

Alcohol dependence: the impact of cognitive behaviour therapy with or without naltrexone on subjective health status

Objectives: To examine the health-related quality of life of alcohol-dependent patients across a 12-week cognitive behaviour treatment (CBT) program and identify whether the patient selection of the anticraving medication naltrexone further enhanced these outcomes. Method: One hundred and thirty-six consecutive alcohol-dependent subjects voluntarily participated and were offered naltrexone, of which 73 (54%) participants declined medication. A matched design was used. Of the 136 subjects, 86 (43 naltrexone and CBT; 43 CBT only) could be individually matched (blind to outcome measures) for gender, age, prior alcohol detoxification and dependence severity. Measures of health status and mental health wellbeing included the Rand Corporation Medical Outcomes Short Form 36 Health Survey (SF-36) and the General Health Questionnaire (GHQ-28). Results: Pre-treatment, all had SF-36 and GHQ-28 scores markedly below national norms. Post-treatment, significant improvement in seven of the eight SF-36 subscales and all of the GHQ-28 subscales occurred, approximating national normative levels. Patients in the CBT + naltrexone group were significantly more likely to have increased days abstinent (p = 0.002) and to complete the program abstinent (p = 0.051). The adjunctive use of naltrexone did not provide additional benefit as reflected in SF-36 and GHQ-28 scores, beyond CBT alone. Conclusions: Patients who completed the CBT-based treatment program reported significant improvements in self-reported health status (SF-36) and wellbeing (GHQ-28). The adjunctive use of naltrexone demonstrated no additional improvement in these measures.

The role of drinking restraint in alcohol dependence: validation of the temptation and restraint inventory in an alcohol dependent sample

Objective: The Temptation and Restraint Inventory (TRI) is commonly used to measure drinking restraint in relation to problem drinking behavior. However, as yet the TRI has not been validated in a clinical group with alcohol dependence. Method: Male (n = 111) and female (n = 57) inpatients with DSM-IV diagnosed alcohol dependence completed the TRI and measures of problem drinking severity, including the Alcohol Dependence Scale and the quantity, frequency and week total of alcohol consumed. Results: The factor structure of the TRI was replicated in the alcohol dependent sample. Cognitive Emotional Preoccupation (CEP), one of the two higher order factors of the TRI, demonstrated sound predictive power toward all dependence severity indices. The other higher order factor, Cognitive Behavioral Control (CBC), was related to frequency of drinking. There was limited support for the CEP/CBC interactional model of drinking restraint. Conclusions: Although the construct validity of the TRI was sound, the measure appears more useful in understanding the development, maintenance and severity of alcohol-related problems in nondependent drinkers. The TRI may show promise in detecting either continuous drinking or heavy episodic type dependent drinkers.

Major Depressive Disorder, Suicidal Ideation, and Suicide Attempt in Twins Discordant for Cannabis Dependence and Early-Onset Cannabis Use

Background: Previous research has reported both a moderate degree of comorbidity between cannabis dependence and major depressive disorder (MDD) and that early-onset cannabis use is associated with increased risks for MDD. Objective: To examine whether associations between both lifetime cannabis dependence and early cannabis use and measures of MDD, suicidal ideation, and suicide attempt persist after controlling for genetic and/or shared environmental influences. Design: Cross-sectional survey of twin pairs discordant for lifetime cannabis dependence and those discordant for early cannabis use. Setting: General population sample of twins (median age, 30 years). Participants: Two hundred seventy-seven same-sex twin pairs discordant for cannabis dependence and 311 pairs discordant for early-onset cannabis use (before age 17 years). Main Outcome Measures: Self-report measures of DSM-IV-defined lifetime MDD, suicidal ideation, and suicide attempt. Results: Individuals who were cannabis dependent had odds of suicidal ideation and suicide attempt that were 2.5 to 2.9 times higher than those of their non-cannabis-dependent co-twin. Additionally, cannabis dependence was associated with elevated risks of MDD in dizygotic but not in monozygotic twins. Those who initiated cannabis use before age 17 years had elevated rates of subsequent suicide attempt (odds ratio, 3.5 [95% confidence interval, 1.4-8.6]) but not of MDD or suicidal ideation. Early MDD and suicidal ideation were significantly associated with subsequent risks of cannabis dependence in discordant dizygotic pairs but not in discordant monozygotic pairs. Conclusions: Comorbidity between cannabis dependence and MDD likely arises through shared genetic and environmental vulnerabilities predisposing to both outcomes. In contrast, associations between cannabis dependence and suicidal behaviors cannot be entirely explained by common predisposing genetic and/or shared environmental predispositions. Previously reported associations between early-onset cannabis use and subsequent MDD likely reflect shared genetic and environmental vulnerabilities, although it remains possible that early-onset cannabis use may predispose to suicide attempt.

Appetitive motivation predicts the majority of personality and an ability measure: a comparison of BAS measures and a re-evaluation of the importance of RST

Our first study develops a measure of appetitive motivation and our second study compares several measures of Gray's (1987) behaviour activation system (BAS) in the prediction of the surface scales of personality. In particular, we were interested in determining the utility of the new appetitive motivation scale and Dickman's functional impulsivity scale. In comparison to other well-known measures, both scales were generally good predictors. We conclude that the appetitive motivation scale is a promising measure of BAS based upon construct validation. Contrary to previous studies which have suggested that BAS is a generally poor predictor of the surface scales of personality, we discovered appetitive motivation to be an important predictor of personality in general. Interestingly, the scale was also predictive of scores on the Baddeley reasoning test. (C) 2003 Elsevier Ltd. All rights reserved.

The appetitive motivation scale and other BAS measures in the prediction of Approach and Active Avoidance

The Appetitive Motivation Scale (Jackson & Smillie, 2004) is a new trait conceptualisation of Gray's (I 970 199 1) Behavioural Activation System. In this experiment we explore relationships that the Appetitive Motivation Scale and other measures of Gray's model have with Approach and Active Avoidance responses. Using a sample of 144 undergraduate students, both Appetitive Motivation and Sensitivity to Reward (from the Sensitivity to Punishment and Sensitivity to Reward Questionnaire, SPSRQ; Torrubia, Avila, Molto, & Ceseras, 2001), were found to be significant predictors of Approach and Active Avoidance response latency. This confirms previous experimental validations of the SPSRQ (e.g., Avila, 2001) and provides the first experimental evidence for the validity of the Appetitive Motivation scale. Consistent with interactive views of Gray's model (e.g., Corr, 2001), high SPSRQ Sensitivity to Punishment diminished the relationship between Sensitivity to Reward and our BAS criteria. Measures of BIS did not however interact in this way with the appetitive motivation scale. A surprising result was the failure for any of Carver and White's (1994) BAS scales to correlate with RST criteria. Implications of these findings and potential future directions are discussed. (C) 2004 Elsevier Ltd. All rights reserved.

Effects of Variation at the ALDH2 Locus on Alcohol Metabolism, Sensitivity, Consumption, and Dependence in Europeans

Background: The low-activity variant of the aldehyde dehydrogenase 2 (ALDH2) gene found in East Asian populations leads to the alcohol flush reaction and reduces alcohol consumption and risk of alcohol dependence (AD). We have tested whether other polymorphisms in the ALDH2 gene have similar effects in people of European ancestry. Methods: Serial measurements of blood and breath alcohol, subjective intoxication, body sway, skin temperature, blood pressure, and pulse were obtained in 412 twins who took part in an alcohol challenge study. Participants provided data on alcohol reactions, alcohol consumption, and symptoms related to AD at the time of the study and subsequently. Haplotypes based on 5 single-nucleotide polymorphisms (SNPs) were used in tests of the effects of variation in the ALDH2 gene on alcohol metabolism and alcohol's effects. Results: The typed SNPs were in strong linkage disequilibrium and 2 complementary haplotypes comprised 83% of those observed. Significant effects of ALDH2 haplotype were observed for breath alcohol concentration, with similar but smaller and nonsignificant effects on blood alcohol. Haplotype-related variation in responses to alcohol, and reported alcohol consumption, was small and not consistently in the direction predicted by the effects on alcohol concentrations. Conclusions: Genetic variation in ALDH2 affects alcohol metabolism in Europeans. However, the data do not support the hypothesis that this leads to effects on alcohol sensitivity, consumption, or risk of dependence.

The implications of simultaneous smoking initiation for inferences about the genetics of smoking behavior from twin data

We examined early social influences across stages of smoking within the context of a twin study using an environmental exposure specific to smoking: whether twins started smoking at the same time (simultaneous smoking initiation: SSI). We expected that SSI would be a good index of shared social influences on smoking initiation. Rates of SSI were indeed significantly higher in MZ twins and in twins who shared peers and classes, as well as in male twins. With the exception of regular smoking in females, we found no significant difference in estimates of genetic and environmental parameters between SSI and non-SSI pairs for any of the smoking measures that we examined (DSM-IV and Fagerstrom HSI measures of nicotine dependence; DSM-IV nicotine withdrawal; heavy smoking; and in males, regular smoking). For regular smoking in females, allowing for additional shared environmental influences associated with SSI only modestly reduced our estimates of additive genetic variance (56% vs. 68%). These results indicate the important social influences that may occur for smoking initiation do not appear to seriously bias estimates of genetic effects on later stages of smoking.