Visual P3 findings in Mission Indian youth: relationship to family history of alcohol dependence and behavioral problems.

Native Americans have some of the highest rates of alcohol abuse and dependence, yet risk factors for problem drinking remain relatively unknown. The amplitude of the P3 component of the event-related potential (ERP) has been suggested to be an index of 'vulnerability to alcoholism', especially when it is elicited by visual tasks in younger individuals. Visual P3 tasks, however, have not been previously investigated in Native American youth. One hundred and four Mission Indian youth between the ages of 7 and 13 years participated in the study. ERPs were collected using two visual target paradigms: a facial discrimination and an estimation of line orientation task. Analyses of covariance revealed that participants with a first degree family history of alcoholism had lower P3 component amplitudes in frontal leads to the facial discrimination task. Lower P3 amplitudes, in posterior areas, were found in the line discrimination task in children who scored above the 75th percentile in delinquent behaviors on the Achenbach Child Behavior Checklist. These findings are consistent with investigations in non-Indian populations demonstrating that the late positive component of the event related potential is sensitive to both familial history of alcohol dependence as well as personal history of externalizing behaviors.

Auditory P3 findings in mission Indian youth.

OBJECTIVE: Native Americans have some of the highest rates of alcohol abuse and dependence, yet potential biological risk factors associated with the problem drinking seen in many tribes remain relatively unknown. In this study, the amplitude of the P3 component of the event-related potential (ERP), a measure associated with risk for alcoholism in European-American youth, was investigated in Mission Indians. METHOD: The study participants were Mission Indian children and adolescents (N = 68, 37 male) between the ages of 7 and 13 years. ERPs were collected using two auditory "oddball" paradigms: an easy and a difficult discrimination task. P3 amplitude and latency were statistically evaluated as a function of age, gender, degree of Native American heritage (NAH) and family history (FH) of alcohol dependence. RESULTS: P3 latency was found to vary as a function of age and gender, with girls demonstrating greater decreases in latency with age than boys. suggesting a faster maturation time. Whereas there were no significant relationships between NAH and P3 latency, those participants with at least one alcoholic parent had longer P3 latencies elicited by the difficult auditory task. No significant relationships were found between P3 amplitude generated to the target tones and any of the variables (age, gender, FH, NAH). CONCLUSIONS: Mean P3 amplitudes and latencies obtained from these Mission Indian youth were within the range of those values reported in the literature for samples of children and adolescents of other ethnicities. Although the amplitude of the P3 ERP measure has been associated with FH of alcoholism in studies of predominantly European-American individuals, P3 amplitudes generated in response to these auditory tasks did not robustly differentiate Mission Indian children and adolescents who may be at higher risk for alcoholism from those presumed to be at lower risk.

ALDH2 status, alcohol expectancies, and alcohol response: preliminary evidence for a mediation model.

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.

ADH2 and alcohol-related phenotypes in Ashkenazic Jewish American college students.

A variety of genetically influenced alcohol-related phenotypes relate to risk for alcohol dependence. In Asians, variation in the alcohol dehydrogenase (ADH2) gene relates to alcohol dependence, alcohol consumption, and reported alcohol-related symptoms, even after controlling for variation in the aldehyde dehydrogenase (ALDH2) gene. The association of ADH2 polymorphisms with alcohol-related behavior, however, has not been well characterized in non-Asians. This study evaluated 84 Ashkenazic Jewish American college students to determine the prevalence of the ADH2*2 allele (0.31). Carriers of ADH2*2 reported significantly fewer drinking days per month. ADH2*2, however, was not related to alcohol use disorders, alcohol-induced flushing and associated symptoms, number of binge drinking episodes in the past 90 days, maximum number of drinks ever consumed, or self-reported levels of response to alcohol. Results suggest that Ashkenazic Jewish Americans with ADH2*2 alleles drink less frequently, which might contribute, in part, to the overall lower rates of alcoholism in this population.

EEG asymmetry: relationship to mood and risk for alcoholism in Mission Indian youth.

BACKGROUND: Left frontal electroencephalogram (EEG) alpha dominance has been hypothesized to be related to depressed mood as well as aversive motivation and emotion. However, few studies have prospectively evaluated electroencephalogram asymmetry during development in high-risk adolescents and children. METHODS: EEG alpha asymmetry was investigated in 134 Mission Indian children who were between 7 and 13 years of age. The relationships between electroencephalogram alpha asymmetry and age, gender, parental history of alcohol dependence, Native American heritage, and mood/ approach behaviors were explored. RESULTS: No significant relationship was found between frontal alpha asymmetry and age, gender, or behavioral measures of depressed mood and/or approach behaviors. However, participants with > or = 50% Native American heritage were significantly more likely to have greater electroencephalogram alpha power in the left frontal cortex than in the right. CONCLUSIONS: The present findings suggest that the hypothesized relationship between EEG alpha asymmetry and measures of depressed mood, aversive motivation, and emotion may not be universal in all age or ethnic groups. Additionally, though the relationship between greater degrees of Native American heritage and alpha asymmetry are not as yet clear, we suggest it may be more related to substance abuse than depression in this population of Mission Indians.

Effects of age and parental history of alcoholism on EEG findings in mission Indian children and adolescents.

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 genetic association with the development of alcohol and other substance use behavior in Asian Americans.

Studies of Asian adults have found that alcohol use and alcohol dependence are related to variation in the aldehyde dehydrogenase (ALDH2) gene. To investigate the association of ALDH2 with the development of drug involvement, the authors analyzed retrospective information about the onset and regular use of alcohol and other substances as reported by 180 Asian American college students. Possession of an ALDH2*2 allele was not related to initiation of alcohol use or having ever been intoxicated, but individuals with ALDH2*2 alleles were less likely to be regular drinkers, were less likely to have engaged in a binge-drinking episode, reported a lower number of maximum drinks consumed in a 24-hr period, and were less likely to have used tobacco regularly than those without this genetic variant. These findings suggest that ALDH2 is associated with the development of not only alcohol-related behavior but other substance use behavior as well.

Binge drinking in Chinese, Korean, and White college students: genetic and ethnic group differences.

Studies of Asian college students have found that rates of binge drinking are associated with variation in the aldehyde dehydrogenase (ALDH2) gene. Chinese and Koreans have different prevalence rates of the ALDH2*2 allele, alcohol use, and alcoholism. The association of ALDH2 status and ethnic group with binge drinking was examined in 328 Chinese, Korean, and White college students. Ethnic group differences were found, with Whites having the highest rate of binge drinking, followed by Koreans and then Chinese. Among Asian participants, ALDH2 status and ethnicity related to binge drinking in an additive manner. Possessing an ALDH2*2 allele and being Chinese were protective factors, and being White and being Korean without an ALDH2*2 allele were risk factors for binge drinking. These results suggest that ALDH2 status, as well as other factors that differ in Koreans and Chinese, but do not interact with ALDH2, are associated with binge drinking among Asians.

Integrating biological and behavioral factors in alcohol use risk: the role of ALDH2 status and alcohol expectancies in a sample of Asian Americans.

Prior studies have shown that the ALDH2*2 genetic variant, most common in individuals of Asian descent, is related to heightened sensitivity to alcohol and can serve as a protective factor against alcohol problems. This study explored the effect of this factor on alcohol expectancies. It was hypothesized that (a) individuals with ALDH2*2 alleles would have lower positive expectancies and higher negative expectancies, (b) expectancies would mediate the ALDH2-drinking relation, and (c) ALDH2 status would moderate the expectancy-drinking relation. Data were collected from 171 Asian American university students. Positive expectancy and ALDH2 status were correlated with alcohol use. Mediation and moderation hypotheses were supported only in the female sample. Results were not significant for negative expectancies. These results indicate that ALDH2 status may protect against drinking by lowering positive expectancies and reducing the expectancy-drinking relationship.

Parental history of alcoholism and problem behaviors in Native-American children and adolescents.

BACKGROUND: 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.

Hangover symptoms in Asian Americans with variations in the aldehyde dehydrogenase (ALDH2) gene.

OBJECTIVE: Hangovers are not experienced by all people and whether they contribute to the development of alcoholism is unclear. One population that might provide some insight into the role of hangover in the etiology of alcohol use disorders is that of individuals of Asian heritage. Certain Asians have lower rates of alcohol use and alcoholism, findings associated with a mutation in the aldehyde dehydrogenase (ALDH2) gene. Asians with ALDH2*2 alleles drink less and are less likely to be alcoholic than Asians without this mutation. Following alcohol ingestion, they exhibit more intense reactions to alcohol and generate higher levels of the metabolite acetaldehyde. This study evaluated hangover symptoms in Asian Americans with variations in the ALDH2 gene. METHOD: Men and women of Chinese, Japanese and Korean heritage (N = 140) were asked about their drinking history and a blood sample was collected for genotyping at the ALDH2 locus. Subjects used a Likert-type scale to estimate their severity of hangover and completed a 13-item hangover scale assessing the frequency of hangover symptoms during the previous 6 months. RESULTS: With abstainers (n = 17) excluded and with the effects of gender and recent drinking history controlled, ALDH2 genotype accounted for a significant amount of additional variability in the estimated severity of hangover score with a similar, but nonsignificant, trend for a five-item subscale score derived from the hangover scale. CONCLUSIONS: These results suggest that Asian Americans with ALDH2*2 alleles may experience more severe hangovers that may contribute, in part, to protection against the development of excessive or problematic drinking in this population.

Evaluation of the self-rating of the effects of alcohol form in Asian Americans with aldehyde dehydrogenase polymorphisms.

OBJECTIVE: In order to easily assess individual differences in response to alcohol, the Self-Rating of the Effects of Alcohol (SRE) form was recently developed and its psychometric properties tested in primarily white subjects. This study aimed to further evaluate the SRE in a population known to have genetically mediated variability in response to alcohol and risk for alcoholism, Asian Americans with ALDH2 polymorphisms. METHOD: Men and women of Chinese, Japanese or Korean heritage between the ages of 21 and 26 years (N = 156) completed the SRE and a blood sample was drawn for genotyping at the ALDH2 locus. RESULTS: SRE results were available from 137 (78 female) subjects. With the effects of gender, body weight, frequency of recent drinking and quantity of recent drinking controlled, ALDH2 genotype still accounted for a significant amount of variability in SRE score in this Asian-American sample. Evaluation of SRE scores 4.5 or higher indicated that a low response to alcohol was associated with ALDH2*1/2*1 genotype, male gender and Korean heritage, all factors associated with increased risk for alcoholism. CONCLUSIONS: These results provide additional support for the SRE as a valid instrument for assessing individual variability in response to alcohol and as a useful measure for identifying individuals at relatively increased or decreased risk for alcoholism based on level of reaction to alcohol.

Influence of alcohol on electrophysiological responses to facial stimuli.

A facial discrimination task adapted for use in an event-related potential paradigm was administered to 15 male subjects following oral administration of placebo and 0.56 g/kg alcohol. The stimuli (digital photographs of males and females with happy, sad and neutral facial expressions) generated a series of waves including a prominent positive potential with a latency between 400-550 msec, designated the P450. Three factor repeated measures multivariate analysis of variance was used to evaluate the effect of alcohol on the amplitudes and latencies of the P450 component to the happy and sad faces. As compared to placebo, following alcohol ingestion, male subjects had decreased P450 amplitudes but only to male happy faces compared to female happy faces. These data suggest that this ERP paradigm may be sensitive to detecting subtle effects of alcohol on brain responses to gender-related affective stimuli.

Electroencephalographic responses to alcohol challenge in Native American Mission Indians.

BACKGROUND: Native Americans have some of the highest rates of alcohol abuse and dependence, yet potential central nervous system risk factors responsible for the problem drinking seen in some tribes remain relatively unknown. METHODS: Background electroencephalographic (EEG) variants and response to alcohol were investigated in 48 Native American Mission Indian men between 18 and 25 years old. RESULTS: Subjects with 50% or greater Native American heritage had a significantly higher proportion of low-voltage EEG variants. Within this sample of Mission Indian men, however, a family history of alcohol dependence was associated with a greater incidence of high voltage alpha EEGs. Mission Indian men also evidenced a "less depressant, more stimulating" response to alcohol as quantified by less alcohol-induced reductions in alpha, greater EEG stability, and increased alcohol-induced beta activity. CONCLUSIONS: These findings demonstrate that certain genetically regulated EEG variants that have been previously associated with risk for alcoholism in Caucasians may also be more common in these Mission Indian men. Additionally, EEG measures of response to alcohol do not provide support for the commonly held idea that Indians are more sensitive to the depressant effects of alcohol.

Medication adherence strategies for drug abusers with HIV/AIDS.

This paper describes two clinical techniques aiming to improve adherence to medications for HIV/AIDS in methadone maintenance patients. The first technique, providing on-site dispensing of antiretroviral medications, enhanced medication adherence but did not produce enduring effects beyond the time of the intervention. To develop a more long-lasting intervention, the programme is experimenting with more individualized medication management, in which a staff member provides assessment and problem solving to help improve medication adherence. Clinical and practical issues are presented--including each technique's aims, screening and recruitment of participants, description of the technique, staff and administrative support issues, and research results. The paper aims to assist staff in drug treatment programmes to implement interventions that can increase adherence to medications for HIV/AIDS.

Determinants of P3 amplitude and response to alcohol in Native American Mission Indians.

Native Americans have some of the highest rates of alcohol abuse and dependence, yet potential biological risk factors associated with the problem drinking seen in some tribes remain relatively unknown. The amplitude of the P3 component of the event-related potential (ERP) is perhaps the most studied electrophysiological "marker" of potential vulnerability to alcohol dependence, yet it has not been investigated in Native Americans. Forty-seven, non-alcohol-dependent Native American Mission Indian men between the ages of 18 and 25 years participated in the study. ERPs were collected at 60 minutes following both alcohol (0.56 g/kg) and placebo intake. No relationship was found between P3 amplitude and degree of Native-American heritage (NAH), or family history (FH) of alcohol dependence. The results of this study did, however, replicate previous findings that the P3 component of the ERP is sensitive to the effects of alcohol. A reduction in the P3a component across the scalp was found in these Native American men following alcohol when compared with placebo ingestion. P3 response to alcohol, although not influenced by a subject's NAH or FH, was influenced by the presence of a polymorphism in the alcohol metabolizing enzyme alcohol dehydrogenase (ADH). Men with an ADH2 x 3 allele had significantly higher amplitude P3 components at placebo and also demonstrated more alcohol-induced reductions in P3 amplitude than men with ADH2 x 1 alleles only. In addition, individuals with low P3 amplitude in the placebo condition had less of a reduction or an actual increase in P3a and P3b amplitudes following alcohol intake. Given that a less intense response to alcohol has been associated with greater risk for the development of alcohol-related problems, these data suggest the presence of certain biological variables within this Native American population that may confer both risk and protection for the future development of alcohol dependence.

Alcohol metabolism in Asian-American men with genetic polymorphisms of aldehyde dehydrogenase.

BACKGROUND: About half of certain Asians have a deficiency of the low-Km aldehyde dehydrogenase (ALDH2) isoenzyme. This deficiency results from inheritance of a mutant ALDH2*2 allele. OBJECTIVE: To determine whether Asian Americans with ALDH2*2 alleles differ from Asian Americans without this mutation in terms of blood levels of alcohol and acetaldehyde after ingestion of a moderate amount of alcohol. DESIGN: Double-blind, crossover study. SETTING: Private research institute. PARTICIPANTS: 35 healthy Asian-American men. Three men who became ill after alcohol ingestion and one who had outlying data were excluded. INTERVENTION: Alcoholic beverage, containing 0.56 g of alcohol per kg of body weight, or placebo beverage, containing 3 mL of alcohol, given orally on separate occasions. MEASUREMENTS: Blood levels of alcohol and acetaldehyde measured before and several times after ingestion of the alcoholic or placebo beverage. RESULTS: Participants with ALDH2*2 alleles had significantly higher blood acetaldehyde levels after ingesting alcoholic and placebo beverages than did participants with ALDH2*1 alleles, despite similar blood alcohol concentrations. CONCLUSIONS: Blood acetaldehyde levels rather than blood alcohol concentration may mediate enhanced alcohol sensitivity among Asians with ALDH2*2 alleles.

The firewater myth and response to alcohol in Mission Indians.

OBJECTIVE: This study aimed to assess empirically the intensity of reaction to alcohol in a group of Native Americans. METHOD: Forty healthy, nonalcoholic Mission Indian men between the ages of 18 and 25 years were tested before and after ingestion of placebo and 0.75 ml/kg of alcohol. Subjective (self-report of feelings) and objective (blood pressure, pulse rate, and plasma cortisol level) measures of intoxication were taken before ingestion of alcohol and placebo and at 15, 30, 60, 90, and 120 minutes after ingestion. Overall effects of alcohol were evaluated, and the responses of subjects with less than 50% Native American heritage (N = 19) were compared with the responses of subjects with at least 50% Native American heritage (N = 21). RESULTS: Alcohol did not produce any significant effects on any of the objective measures of intoxication; however, the subjects reported significant subjective effects of alcohol. Subjects with at least 50% Native American heritage reported less intense effects of alcohol than did those with less than 50% Native American heritage, despite equivalent blood alcohol concentrations. CONCLUSIONS: These results contradict the "firewater myth"--the theory that Native Americans are more sensitive to the effects of alcohol. Rather, the data indicate that Mission Indian men generally may be less sensitive to alcohol's effects, a physiological characteristic that has been shown to be associated with a greater risk for alcoholism in Caucasian populations. In addition, individuals with a greater percentage of Native American heritage may be less sensitive to the subjective effects of alcohol than individuals with a smaller percentage of Native American heritage.

Alcohol dehydrogenase polymorphisms in Native Americans: identification of the ADH2*3 allele.

Alcohol dehydrogenase (ADH) polymorphisms were evaluated among 95 Native American Mission Indians. Approximately equal frequencies of ADH3*1 and ADH3*2 alleles were found. Twelve individuals were heterozygous for ADH2*3, an allele previously identified only in persons of African origin. None of the individuals with ADH2*3 alleles was of purely Native American descent, although none had known African ancestry. These results suggest that these candidate genes deserve broader study among Native Americans and may provide increased understanding of the likely polygenic contributions to alcohol-related disorders in this population.