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BackgroundDual systems theories suggest that greater imbalance between higher reward sensitivity and lower cognitive control across adolescence conveys risk for behaviors such as heavy episodic drinking (HED). Prior research demonstrated that psychological analogues of these systems, sensation seeking and premeditation, change from childhood through emerging adulthood, and each has been independently linked with HED. However, few studies have assessed whether change over time in these developing analogues is prospectively associated with HED. Moreover, we know of no research that has shown whether within-person differences between higher sensation seeking and relatively lower premeditation across the adolescent period predict HED in emerging adulthood.MethodsProspective data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study (n=715) were used to examine the association of sensation seeking and premeditation with HED among adolescents ages 16 to 20years. We used novel applications of latent difference score modeling and growth curve analysis to test whether increasing sensation seeking, premeditation, and their imbalance over time are associated with HED across the study period, and whether these associations differed by sex.ResultsWhereas premeditation increased linearly from adolescence through emerging adulthood across sexes, males reported growth and females reported decline in sensation seeking. Sensation seeking in adolescence (and not premeditation) was associated with higher levels of HED by emerging adulthood. Importantly, greater imbalance between sensation seeking and premeditation was associated with higher levels of HED by emerging adulthood though we note that variability capturing this imbalance correlated highly (r=0.86) with baseline levels of sensation seeking.ConclusionsDevelopmental imbalance between higher sensation seeking and lower premeditation in late adolescence may be a risk factor for greater HED in emerging adulthood.

Background An early age of drinking initiation (ADI) has been associated with increased risk for alcohol use disorders (AUDs), but the consistency of this risk across diverse samples has not been well studied. The purpose of this study was to examine whether the pathway from ADI to AUD symptoms by early adulthood is moderated by ethnicity and possessing an alcohol-metabolizing gene ALDH2*2 variant allele. Methods We used multigroup structural equation modeling, including 5 groups split by ethnicity and ALDH2*2, to examine the consistency of the path from ADI to AUD symptoms in 604 Chinese-, Korean-, and White-American college students. We further examined the effects of ALDH2*2, ethnicity, and their interaction in Asians to better understand their unique contributions to the moderation. Results The association between ADI and AUD symptoms was moderated, with ADI negatively associated with AUD symptoms among Koreans without ALDH2*2 and Whites, but not among Koreans with ALDH2*2 or Chinese regardless of ALDH2*2. Both ALDH2*2 and ethnicity within Asians contributed unique variability in the effect. Conclusions Ethnicity and ALDH2*2 altered the relationship of ADI as a risk factor for AUD symptoms. Being Chinese and possessing an ALDH2*2 allele within Koreans both buffered against the risk for AUD symptoms associated with earlier ADI, indicating that this relationship can be attenuated by protective factors.

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.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.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.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.

Background A mechanistic model has been proposed for how alcohol metabolizing gene variants protect individuals from the development of alcohol use disorders, with heightened sensitivity to alcohol being an early step (endophenotype) in this model. The present study was designed to determine whether possession of two alcohol metabolizing genes variations, the aldehyde dehydrogenase ALDH2*2 allele and the alcohol dehydrogenase ADH1B*2 allele, was associated with self-reported sensitivity to alcohol at low doses and at initial use.

Theories of alcohol-related learning propose that biological factors provide a substrate for individual variability in the reinforcement value of alcohol, which can manifest as differences in alcohol-related cognitions (e.g., Goldman et al., 1999; 2006; Kuntsche et al., 2005; Wiers et al., 2009). To date, studies evaluating genetic influences on alcohol cognitions are generally consistent with this possibility. For example, twin studies suggest moderate heritability for alcohol expectancies (e.g., Agrawal et al., 2008; Slutske et al., 2002) and drinking motives (Agrawal et al., 2008; Prescott et al., 2004). Additionally, molecular genetic studies provide initial evidence for associations of genetic variants and alcohol cognitions. Most of these studies have examined alcohol expectancies (i.e., anticipated effects of alcohol; Goldman et al., 1999), which have been associated with variation in the alcohol metabolizing genes ALDH2 (Hahn et al., 2006; Hendershot et al., 2009a; McCarthy et al., 2000; 2001) and ADH1B (Ehlers et al., 2003), as well as with GABRB3 (Young et al., 2004). Drinking motives, which index positive and negative reinforcement reasons for drinking, are also presumed to reflect biological influences (Kuntsche et al., 2005) and appear to show higher heritability than alcohol expectancies (Agrawal et al., 2007). Although few studies have examined genetic associations with drinking motives, a recent study found associations of the OPRM1 A118G polymorphism with enhancement and coping motives for alcohol use in adolescents (Miranda et al., 2010). OPRM1 A118G has also been linked to automatic approach biases toward alcohol cues, suggesting possible associations of OPRM1 with implicit (i.e., automatic) motivational processes (Wiers et al., 2009). Cognitive and learning theories of alcohol use also emphasize the importance of self-efficacy, or the perceived ability to self-regulate drinking behavior. Drinking refusal self-efficacy, which is implicated in the risk for alcohol use disorders (Oei et al., 2005), has been associated with the ANKK1 TaqI A and GABRB3 G1 alleles (Connor et al., 2008; Young et al., 2004). In sum, there is both theoretical (Goldman et al., 1999; 2006) and empirical support that biological factors might account for variance in alcohol-related cognitions. Importantly, there is also some evidence that alcohol cognitions can partly mediate genetic influences on alcohol-related phenotypes (Agrawal et al., 2007; Hendershot et al., 2009a; McCarthy et al., 2000; Miranda et al., 2010). Whereas cognitive-behavioral theories predict joint influences of expectancies, motives and self-efficacy on drinking behavior (e.g., Engels et al., 2005; Witkiewitz and Marlatt, 2004), genetic influences are rarely modeled in these contexts (e.g., Hendershot et al., 2007; Young et al., 2004). Moreover, few efforts have been made to include theoretically relevant endophenotypes in the context of cognitive-behavioral models. For example, physiological sensitivity to alcohol is a heritable endophenotype that is frequently examined in relation to genetic risk for alcohol dependence (e.g., Joslyn et al., 2008; Schuckit et al., 2004). Because alcohol sensitivity is proposed to influence alcohol expectancies and drinking motives (Goldman et al., 1999; Kuntsche et al., 2005) and may predict drinking in part through expectancies (Schuckit et al., 2005), this construct is an appealing endophenotype for studies addressing biological influences on alcohol-related cognitions. The current study evaluated a cognitive model of genetic influences on drinking behavior, focusing on ALDH2 genotype. ALDH2 encodes the mitochondrial aldehyde dehydrogenase (ALDH) enzyme, the principal catalyst for oxidation of acetaldehyde during alcohol metabolism. A single nucleotide substitution at exon 12 (rs671) results in a variant allele (ALDH2*2) that encodes a functionally inactive ALDH enzyme subunit, thereby limiting oxidation of acetaldehyde during alcohol metabolism. ALDH2*2 is associated with higher levels of post-drinking acetaldehyde, increased sensitivity to alcohol (Edenberg, 2007; Peng and Yin, 2009), and significantly reduced rates of heavy drinking and alcohol dependence (Luczak et al., 2006). Few studies have evaluated cognitive or learning mechanisms relevant for these associations; however, it is proposed that biological factors (including alcohol sensitivity) can influence the subjective reinforcement value of alcohol by altering rewarding or punishing effects of consumption (e.g., Brown et al. 1999; Goldman et al., 1999). Exposure to these contingencies during drinking events is presumed to result in learned associations that can be indexed as cognitive representations of the reinforcement value of alcohol (c.f. Goldman et al., 1999). Consistent with this model, previous studies have found that ALDH2*2 is associated with alcohol expectancies, which account for significant indirect effects of ALDH2 on drinking outcomes (Hendershot et al., 2009a; McCarthy et al., 2000). The goal of the current study was to evaluate a relatively more comprehensive cognitive model of ALDH2 and drinking behavior. The current model was informed by social learning theories of alcohol use (e.g., Abrams and Niaura, 1987; Cooper et al., 1988), which emphasize the importance of drinking motives and self-efficacy (in addition to expectancies) in predicting drinking behavior. Drinking motives have been invoked as a final common pathway for alcohol use and are often found to mediate associations of expectancies with drinking (Cooper et al., 1995; Kuntsche et al., 2005; 2007). Drinking refusal self-efficacy is frequently shown to predict drinking independent of alcohol expectancies (Engels et al., 2005; Oei & Jardim, 2007), but is not frequently conceptualized as a mediator of expectancies. Based on these considerations, the current study tested the following hypotheses: a) ALDH2*2 would be associated not only with self-reported alcohol sensitivity and alcohol expectancies, but with lower drinking motives and higher drinking refusal self-efficacy, b) cognitive factors and alcohol sensitivity would account for the association of ALDH2 with drinking behavior, such that the ALDH2-drinking association would not be significant when accounting for these factors in a multivariate model, and c) associations of ALDH2 with drinking motives and alcohol sensitivity would be mediated through expectancies, whereas the association of ALDH2 with drinking refusal self efficacy would not involve expectancies. Structural equation modeling (SEM) was used to evaluate the model in relation to heavy drinking and a prospective measure of alcohol-related problems in a sample of Asian-American young adults.

Background: Risk and protective factors for alcohol use disorders (AUDs) are complex and reflect both environmental and genetic factors. Genetic components account for about 50% of the variation and influence several phenotypes, including the level of response (LR) to alcohol as well as alcohol-metabolizing enzyme polymorphisms. Variations in the ADH1B and ADH1C genes may influence the LR to alcohol by increasing levels of acetaldehyde during alcohol metabolism, although most data on this question come from Asian populations. Methods: This study evaluated associations of ADH1B and ADH1C genotypes in a non-Asian sample. Participants (N=117, 69.2% female) were 18- to 29-year-old men and women, primarily Caucasian (70.1%) and black (26.5%), recruited in San Diego, California. The Semi-Structured Assessment for the Genetics of Alcoholism Interview was used to assess demographic, substance use, and psychiatric history information, and the Family History Assessment Module was used to determine first-degree family history of alcohol dependence. An alcohol challenge paradigm was used to gather data on the LR to alcohol over 210 minutes. Results: Participants with the ADH1B*1/*2 genotype had a higher LR to alcohol early in the alcohol challenge (i.e., 30, 60, and 90 minutes after drinking) as measured by both alcohol-related changes in subjective feelings of intoxication and body sway, even when controlling for sex and Russian/Eastern European ancestry. A similar trend was seen for ADH1C*1/*1 genotype, although the results were not significant. Conclusions: These findings suggest that studies searching for genes relating to the LR to alcohol as a vulnerability factor for AUDs should consider controlling for ADH1B genotype, as the ADH1B*2 allele could obscure the impact of other genetic polymorphisms.

Background: A genetic variant in the alcohol-metabolizing enzyme (aldehyde dehydrogenase;ALDH2*2 allele), common in individuals of Asian heritage, has been associated with both physiologic response to alcohol and alcohol consumption. Prior research has also demonstrated that those with ALDH2*2 alleles have lower positive alcohol expectancies than those without these alleles. This preliminary study was designed to test whether the level of response to alcohol is the mechanism by which ALDH2 status may affect alcohol expectancies. Methods: Data were collected from 32 Asian American college students (14 women and 18 men). By use of a randomized, double-blind design, participants were administered oral placebo and alcohol at separate laboratory sessions. Data included blood tests to establish ALDH2 status, questionnaire measures of demographic information and alcohol expectancy, and several physiologic measures collected after placebo and alcohol administration. Results: ALDH2 status was related to alcohol response measures for both men and women. ALDH2 status was also related to tension reduction expectancies for women and to expectancies for cognitive behavioral impairment for men. In the male sample, the ALDH2/expectancy relationship was fully explained by the level of response to alcohol. Conclusions: These results represent a first step in understanding the mechanisms by which genetic factors, such as ALDH2 status, can affect alcohol-related learning.

Background: Many, but not all, Native American tribes have some of the highest rates of alcohol abuse and dependence. Yet, risk factors for the development of problem drinking in these high risk groups remain largely unknown. In primarily Euroamerican populations, electrophysiological variables have been associated with risk for alcoholism. The EEG has a specific developmental time course that has been described in a diverse set of ethnic groups, but it has not been described in Native American youth. In addition, the relationship between EEG development and risk for alcoholism in Indian youth has not been previously studied. Methods: Clinical ratings and spectral characteristics of the resting EEG were investigated in 140 Native American Mission Indian children and adolescents between the ages of 7 and 13 years. The specific aims of the study were to (1) investigate the relationship of age and gender with EEG spectral variables to determine if this population conforms to similar trends from previously published data in other ethnic groups and (2) to determine whether children with a parental history of alcoholism differ from those without alcoholic parents on EEG spectral parameters. Results: No excess of abnormal EEG activity was found in this sample of Native American youth. Age, but not gender, was found to have a significant effect on EEG spectral characteristics with younger children (7–11 years old), having significantly more power in slow activity (0.5–7.5 Hz) and in alpha power (8–12 Hz) as well as slower alpha frequencies than older children (12–13 years old). Consistent with other studies of Native American youth, 66% of the children and adolescents participating in this study had at least one parent who had a lifetime diagnosis of alcohol dependence. However, an ANCOVA that covaried for age and gender revealed no significant differences in power or frequency characteristics of the EEG on the basis of parental history of alcoholism. Conclusions: These studies suggest that this sample of Mission Indian children, despite high levels of parental alcohol dependence and low socioeconomic status, show normal EEG development. As yet, no relationship has been found between any specific EEG phenotype and parental history of alcoholism in this population, however, further EEG maturation may be necessary before any relationships can be fully delineated.

A positive family history of alcoholism is one of the most consistent and powerful predictors of a person's risk for developing this disorder. This finding has stimulated much research on etiological vulnerability factors and mechanisms by which children of alcoholic parents are at high risk for developing alcohol-related problems. In primarily Euro-American samples, parental alcoholism has been associated with a variety of negative outcomes for children and adolescents, including problematic behavior. Native-American Indians, in addition to high rates of alcoholism and alcohol-related mortality, have the highest prevalence of a positive family history for alcoholism of all ethnic groups in the United States. METHODS: This study used the Achenbach Child Behavior Checklist (CBCL) to evaluate behavioral problems in 96 Mission Indian children and adolescents based on the presence or absence of parental alcohol dependence and sex of the offspring. RESULTS: Consistent with previous research, results indicated a high prevalence of a positive family history of alcoholism in these Native-American youths. Seventy-four percent of the offspring had either one or both parents with alcohol dependence (children of alcoholics). Only 7% had no first- or second-degree alcoholic relatives. Results indicated that sons of alcoholics scored significantly higher on the Total Behavior Problem scale, as well as the Internalizing and Externalizing scales, of the CBCL than sons of nonalcoholics, whereas there were no significant differences in CBCL scores between daughters of alcoholics and daughters of nonalcoholics. It is noteworthy that scores on the CBCL for Mission Indian children of alcoholics were comparable to scores in the published literature of children of alcoholics of other ethnicities. In addition, a relatively low percentage of youths were identified with significant levels of behavioral problems. CONCLUSIONS: These findings suggest that sons of alcoholics of Mission Indian heritage experience more problems than sons of nonalcoholics, but also suggest that Mission Indian children of alcoholics are not more vulnerable to behavioral problems than children of alcoholic parents of other ethnic backgrounds.

Native Americans, as a group, have a high prevalence of alcohol abuse and alcohol dependence, although specific risk factors for alcoholism among this population have yet to be clearly identified. One set of factors that may contribute to the development of alcoholism are expectations of alcohol's effects. Previous research has shown that heavy drinkers and alcoholics have higher alcohol-related expectancies. Some studies have also shown an association between alcohol expectancies and a positive familial history of alcoholism. To examine factors that are related to expectations of alcohol's effects in a Native American population, this study evaluated healthy, nonalcoholic Mission Indian men between the ages of 18 and 25 years using the short form of the Alcohol Expectancy Questionnaire (AEQ). The influence of recent drinking history, family history of alcoholism, and degree of Native American heritage on alcohol-related expectancies was determined using regression analyses for the total AEQ score and for each of the six AEQ subscales. Recent drinking history accounted for a significant proportion of the variance in the total score, as well as scale I (global positive changes) and scale VI (arousal and power) of the AEQ. Degree of Native American heritage and family history of alcoholism did not account for a significant amount of variability in alcohol expectancies. These results suggest that, consistent with findings in other populations, alcohol expectancies are related to drinking patterns in Mission Indians. However, no association with two other potential risk factors were found in this sample of Native Americans.

Background: Variations in the alleles for the alcohol-metabolizing enzymes have been shown to influence risk for alcohol dependence. One variant, ADH1B*3, is observed almost exclusively in populations of African ancestry and has been shown to be associated with reduced rates of alcohol dependence. We conducted an alcohol challenge study to test whether ADH1B*3 is associated with differences in subjective and physiological response to alcohol. Method: We administered a moderate dose of alcohol (0.72 g/kg for males, 0.65 g/kg for females) to a sample of African-American young adults (n = 91; ages 21 to 26). Participants were genotyped for ADH1B, as well as additional polymorphisms that might contribute to alcohol response. Breath alcohol concentration, self-reported sedation and stimulation, and pulse rate were assessed prior to alcohol administration and for 2.5 hours following administration. Results: ADH1B*3 was associated with higher levels of sedation and a sharper increase in pulse rate immediately following alcohol consumption. Conclusions: These findings suggest that the lower rates of alcohol dependence in those with ADH1B*3 alleles may be because of differences in alcohol response, particularly increased sedation.

The effects of ethanol administration (0, 0.25, 0.5, 0.75 and 1.0 g/kg intraperitoneal) were examined in a conflict test in 24 alcohol-preferring (P)-rats, 17 alcohol-nonpreferring (NP)-rats, and 24 heterogeneous Wistar rats. The conflict test was a modified Geller-Seifter procedure employing an unpunished random interval 30-sec component and an incremental shock conflict component. Heterogeneous Wistar rats displayed significant increases in punished responding with doses of 0.5, 0.75, and 1.0 g/kg of ethanol. P-rats did not show a significant increase in punished responding until 0.75 g/ kg ethanol. NP rats displayed significant increases in punished responding with all doses tested (0.25, 0.5, and 0.75 g/kg). There were no group differences in the effects of ethanol on unpunished responding. Thus NP-rats were more sensitive and P-rats were less sensitive to the anticonflict effects of ethanol than heterogeneous Wistar rats. The results suggest that the P and NP rats may show a profile of sensitivity to the anticonflict effects of ethanol similar to the sensitivity to the intoxicating effects of ethanol observed in family history positive and family history negative human subjects.