P3 amplitudes in two distinct tasks are decreased in young men with a history of paternal alcoholism

Visual event-related potentials (ERPs) were obtained in two groups of young adult male subjects: One group (N = 24) considered to be at high risk for alcoholism due to paternal alcoholism and the second group (N = 26) with no family history of alcoholism. Results presented here were obtained during a baseline (no drug) condition. The ERP tasks both were target detection paradigms, but differed in several respects. One paradigm involved continuous participation in a distracting tracking task, but used an easily interpreted target stimulus. The second task involved no distractions, but entailed more complex stimuli. Both paradigms utilized level of task difficulty as an experimental variable. The results from both tasks were quite similar and demonstrated significantly lower ERP amplitudes in the high risk compared to the low risk group. Reaction times to target stimuli did not discriminate group membership, but were related to perceived task difficulty. Task difficulty was not a useful variable in discriminating group membership.     

EVENT-RELATED POTENTIALS ELICITED BY INFREQUENT NON-TARGET STIMULI IN YOUNG CHILDREN OF ALCOHOLICS: FAMILY HTSTORY AND GENDER DIFFERENCES

This article analyses the visual and auditory event-relatedpotentials (ERPs) elicited by infrequent non-target stimuliin young children with alcoholic fathers. The aim was to studythe characteristics of the ERP waves specifically evoked bystimuli which capture the attention of the subject in youngones at risk for alcoholism, and to assess the effect of samplefactors which can modulate these characteristics, namely familyhistory of alcoholism and gender. There were no differencesrelated to risk for alcoholism on the auditory ERPs. However,males and females with a multigenerational family history ofalcoholism showed significant differences on visual ERP latencies,although different waves were affected for each gender. Femalesshowed a larger latency of the visual frontal negative wave,Nc, and males showed a larger latency of the visual parietocentralP300 wave.     

Familial density of alcoholism: effects on psychophysiological responses to ethanol

Recent research findings suggest that the patterning of familial alcoholism may critically determine ethanol sensitivity and severity of alcohol-related problems in the offspring. The present study examined the effects of familial alcoholism density on psychophysiological responses to ethanol administration in college males. Subjects with a positive family history of alcoholism were classified into affected biological father only (LD-FHP) versus both father and at least one second-degree affected relative (HD-FHP), and were compared to family history negative (FHN) subjects. Subjects received 1 g/kg ethanol or placebo in a double-blind procedure. A battery of subjective, physiological and psychomotor measures were collected once prior to and four times following drink administration. HD-FHP subjects showed significantly greater subjective effects, body sway and skin conductance after alcohol ingestion than either FHN or LD-FHP subjects; in contrast, there was no difference on any measure for LD-FHP versus FHN subjects. Our findings of increased ethanol sensitivity as a function of familial density of alcoholism strongly suggest the importance of carefully defining family history characteristics in all studies examining potential markers or risk factors for alcoholism.     

P300, alcoholism heritability, and stimulus modality.

The P300 event-related brain potential (ERP) was elicited with auditory and visual stimuli from members of 13 families who were at high risk (HR) for alcoholism (father diagnosed as alcoholic) and 13 families at low risk (LR) for alcoholism. Each family consisted of a father, mother, and at least two biological children. The intrafamily member correlations (father vs. child, mother vs. child, child vs. child) for P300 amplitude were obtained for 15 electrode sites. P300 amplitude from auditory stimuli was not correlated among HR family members, but was positively correlated among LR family members. P300 amplitude from visual stimuli was positively correlated among both HR and LR family members. When taken in conjunction with previous findings, the present results suggest that P300 amplitude from auditory stimuli may not be as reliable as ERPs from visual stimuli for the assessment of alcoholism heritability.     

Sweet liking and family history of alcoholism in hospitalized alcoholic and non-alcoholic patients

The present study was designed to test the hypothesis that preference for stronger sweet solutions may be associated with the genetic risk for alcoholism. Thirty-two male patients with alcohol dependence admitted for alcoholism in-patient treatment and 25 non-alcoholic control subjects were used in the study. Hedonic response to sweets was evaluated using the sweet preference test. Family history of alcoholism was evaluated using a Russian version of the Michigan Alcoholism Screening Test modified for the assessment of the alcohol-related behaviour of the subject's biological father. Similar to our previous findings, alcoholics were far more likely to prefer the highest offered sucrose concentration (0.83 M), compared to non-alcoholic controls. Such preference was determined by two factors: positive family history of alcoholism and alcoholic status. Statistically, these factors contributed to the likelihood of preferring sweet solutions independently. Therefore, the effects of these factors may enhance each other. These findings support the hypothesis that preference for a stronger sweet solution is associated with a paternal history of alcohol dependence and may reflect a genetic predisposition to alcoholism.     

Family thinking in prevention of alcoholism.

Prevention of alcoholism is considered through family therapy interfering with the transgenerational transmission. A theoretical structure is offered which argues that unless alcoholism is a strictly constitutional trait, genetically transmitted (for which there is inconclusive evidence), then intervention in the family through treatment offers a potential for breaking the chain.Evidence that alcoholism is familial is reviewed in terms of physiologic predisposition and family structure. The history and theoretical base for family thinking and family therapy are presented. The way in which these concepts apply to alcoholic families and the way alcoholic families reflect and reinforce symptoms of alcoholism are described.How intervention in family process can interrupt the continuation of alcohol abuse and change unhealthy patterns that promote alcohol abuse is described in terms of actual experience as well as theory. It is recommended that family thinking be introduced and encouraged in treatment programs, alcohol education, and public information about alcoholism.     

Pharmacogenetic strategies for studying alcohol dependence

The importance of genotypic differences in the determination of sensitivity to ethanol, tolerance development and physical dependence susceptibility is achieving ever greater recognition. It is now generally accepted by investigators studying the biochemical and physiological bases for alcoholism that genotype can influence all these different aspects of sensitivity to the effects of ethanol. Although there is convincing evidence that susceptibility to alcoholism is inherited in man, we have no idea what it is that is inherited [2, 7, 19, 24, 31]. By examining a family history for a particular individual, we can identify individuals at familial risk for developing problems with alcohol abuse. However, environmental as well as genetic factors are important in determining who does and who does not become an alcoholic [4]. Thus, one critical need is for a genetic marker for alcoholism. Since the search for such markers in human research is both expensive and time-consuming, this has led to the use of animal models for alcoholism. Animal models are particularly helpful for genetic research since their genetics are well understood and can be specifically tooled to the task at hand. The goal of this paper is to illustrate the principal genetic methodologies that have been employed to study the human and animal pharmacogenetics of alcohol, and to identify future directions in this area.     

The TaqI A DRD2 polymorphism in type II alcohol dependence: a marker of age at onset or of a familial disease?

Cloninger's type II is a severe, early-onset, male-limited, and genetically influenced, impulsive form of alcoholism. Significant association has been reported between the A1 allele of the D2 dopamine receptor (DRD2) gene, substance misuse and personality traits of impulsivity and novelty seeking. We assessed the association between the TaqI A DRD2 gene polymorphism with Cloninger's typology and family history of alcohol abuse, which is thought to be more frequent in type II alcoholics. Fifty-one male alcohol-dependent patients were discriminated between type I and type II according to age at onset of alcohol-related problems and interviewed about family history of alcoholism. The associations between DRD2 (A1 or A2 alleles), family history, and typology were assessed by Pearson's chi-square test. Although typology was not associated with the studied polymorphism, a higher rate of general family history of alcohol abuse was still observed in type II patients (χ²₁ = 4.53; P = .033). Furthermore, the A1 allele of the DRD2 was significantly associated with paternal history of alcoholism (χ²₁ = 4.66; P = .031) and male, first-degree, collateral history of alcoholism (χ²₁ = 4.40; P = .036). Age at onset of alcohol-related problems as main discriminator between type I and type II alcohol dependence does not seem to be associated by the TaqI A DRD2 polymorphism. However, the A1 allele of the DRD2 may be a marker of male familial alcoholism, which has been associated with type II alcohol dependence.     

Rates of ethanol metabolism decrease in sons of alcoholics following a priming dose of ethanol.

Rapid changes in rates of ethanol metabolism in response to acute ethanol administration have been observed in animals and humans. To examine whether this phenomenon might vary by risk for alcoholism, 23 young men with a positive family history of alcoholism (family history positive [FHP]) were compared to 15 young men without a family history of alcoholism (family history negative [FHN]). Rates of ethanol metabolism were measured in all subjects first after an initial ethanol dose (0.85 g/kg) and then, several hours later, a second dose (0.3 g/kg), and the two rates were compared. The two groups of subjects were similar in their histories of ethanol consumption. FHP subjects demonstrated faster initial rates of ethanol metabolism, 148+/-36 mg/kg/h, compared to FHN subjects, 124+/-18 mg/kg/h, P=.01. However, FHN subjects increased their rate of metabolism by 10+/-27% compared to a decrease of -15+/-24% in FHP subjects, P=.007. Fifty-two percent of the FHP and none of the FHN subjects exhibited a decline in metabolic rate of 20% or more, P=.0008. Since a significant proportion of FHP subjects exhibited a decrease in the second rate of ethanol metabolism, these preliminary data might help to partly explain why FHP individuals differ in their sensitivity to ethanol and are more likely to develop alcohol dependence.     

P300 from normals and adult children of alcoholics

The P300 event-related brain potential (ERP) was obtained from 24 pairs of undergraduate male subjects. One member of each pair reported having a father who was alcoholic (FH+), the other reported no alcoholic family member (FH-). Pairs were matched on height, weight, academic performance, and personal drinking history. Three auditory task situations were employed which manipulated stimulus discrimination difficulty. All tasks employed 20% target and 80% standard tones randomly presented with the subjects required to move their index finger whenever a target tone was detected. No differences in P300 amplitude or latency were obtained between the groups. FH+ subjects tended to demonstrate decreased amplitudes with increased amounts of reported alcohol consumption but only for the most difficult task. The results of the present study suggest that the relationship between the P300 and the heritability for alcoholism is not yet clear and may be modulated by differences in task requirements, subject populations, and personal drinking history.     

Event-related potential responses to alcohol-related stimuli in African-American young adults: relation to family history of alcoholism and drug usage

AIMS: To use event-related potentials (ERPs) to investigate the response to alcohol-related stimuli in African-American young adults. METHODS: ERPs to an object recognition task, that included pictures of objects, food and alcohol-related and non-alcohol-related drinks as stimuli, were obtained in 81 African-American young adult men and women (18-25 years old) without a personal history of alcohol dependence. Information on: psychiatric diagnoses, personal drinking and drug use history, and familial history of alcoholism was also obtained. RESULTS: Family history was found to be associated with lowered P3 components and higher N1 components in response to the non-alcohol-related drinks. Additionally, an exploratory analyses revealed that lower amplitude N1 components were generated in response to alcohol-related stimuli in regular marijuana users compared with non-regular users. No associations of N1 or P3 amplitudes with conduct disorder symptoms or current drinking status were found in this population. CONCLUSIONS: These studies demonstrated that family history is significantly and selectively associated with lower P3 amplitudes in this group of young adult men and women of African-American heritage. Additionally, current usage of marijuana and alcohol do not modify P3 amplitudes. However, regular marijuana use may diminish N1 response to alcohol-related stimuli, whereas, family history of alcoholism may augment N1 responses. Taken together these studies further suggest that ERPs can provide specific information on alcoholism risk as well as use of other misused drugs.     

Effects of stress,acute alcohol treatment,or both on pre-pulse inhibition in high- and low-alcohol preferring mice

Pre-pulse inhibition of the acoustic startle reflex (PPI) is a measure of sensorimotor gating frequently used to assess information processing in both humans and rodents. Both alcohol and stress exposure can modulate PPI, making it possible to assess how stress and alcohol interact to influence information processing. Humans with an increased genetic risk for alcoholism are more reactive to stressful situations compared to those without a family history, and alcohol may have stress-dampening effects for those with high genetic risk. The purpose of the present study was to examine the effects of stress, acute alcohol exposure, or both on PPI in male and female mice selectively bred for high- (HAP2) and low- (LAP2) alcohol preference. Experiment 1 assessed the effects of various doses of acute alcohol on PPI. Experiments 2 and 3 assessed the effect of 10 days of restraint stress on subsequent PPI tested at 30 min (Experiment 2) or 24 h (Experiment 3) following the termination of stress exposure. Experiment 3 also examined the effects of acute alcohol treatment (0.75 g/kg) on PPI in mice previously exposed to stress or no stress. Results indicate that 0.75 and 1.0 g/kg doses of alcohol increased PPI in HAP2 but not LAP2 mice. When PPI was tested 30 min after stress exposure, stressed HAP2 mice showed a trend toward decreased PPI and stressed LAP2 mice showed a trend toward increased PPI. The combination of stress and alcohol treatment did not alter PPI in either line 24 h following the termination of stress exposure, suggesting that alcohol does not ameliorate the effect of stress on PPI. Stressed LAP2 mice had increased basal circulating corticosterone on the final stress exposure day compared to non-stressed LAP2 mice, and no difference was found between stressed and non-stressed HAP2 mice. The results suggest that high genetic risk for alcoholism may be related to increased sensitivity to alcohol and stress effects on PPI, and this sensitivity could signify an endophenotype for increased genetic risk to develop alcoholism.     

Drinking variables, affective measures and neuropsychological performance: familial alcoholism and gender correlates

The relationships between five measures of alcohol consumption and five summary measures of diverse neuropsychological test performances were studied in 76 male and 67 female alcoholics as a function of family history of alcoholism and affective symptomatology. No significant relationships were obtained between drinking variables and neuropsychological performance scores for the overall groups of male and female alcoholics. In family history positive (FH+) males, correlations between a number of drinking variables and neuropsychological measures neared significance. The Beck Depression Inventory (BDI) scores correlated most strongly with the overall impairment index in both family history positive (FH+) and family history negative (FH-) alcoholics. Depression and anxiety scores in the female alcoholics significantly correlated with three of the five alcohol consumption variables. Possible confounding factors in the relationships between alcohol intake measures and cognitive functioning were discussed.     

P3 in young boys as a predictor of adolescent substance use

Event-related potentials were recorded during a visual, continuous performance task from 36 boys before use of alcohol or other drugs began. The boys were sons of 13 recovering alcoholics who themselves had a family history of alcoholism, 11 nonalcoholics with a family history of alcoholism, and 12 nonalcoholics with no family history of alcoholism. Four years after electrophysiological assessment, a behavioral questionnaire was administered (mean age = 16.1 years). A Substance Use score was derived from reported use of alcohol and other drugs, and from highly correlated delinquent behavior scores. P3s of lowest amplitude were associated with the highest adolescent Substance Use. The combination of reduced amplitude and prolonged latency of both target and nontarget P3 significantly predicted adolescent Substance Use scores after correction for subjects' age. Although this is the first electrophysiological predictor of adolescent substance use we are aware of, the effect was small, indicating the utility of P3 as a vulnerability marker for substance abuse disorders is likely to depend on its joint use with other measures.     

Event-related potentials in alcoholic fathers and their sons

ERPs were recorded during a simple color discrimination and a more difficult visual continuous performance task (CPT) from three father-son (n = 15) pair groups: recovering alcoholics with a family history of alcoholism and their sons (A+), nonalcoholics with a family history of alcoholism and their sons (NA+), and nonalcoholics with no family history of alcoholism and their sons (NA-). The sons, aged 8 to 12, had not begun drinking or using other drugs. Groups were matched on age, education and socioeconomic status. There were two principal findings. Compared to nonalcoholic groups, both A+ sons and fathers exhibited increased latency and decreased amplitude of P3 for the difficult task, but not for the easy task. This result helps to explain previous inconsistencies in the literature, and strengthens the suggestion that one indication of a vulnerability to develop alcoholism is an abnormal P3, when elicited by an appropriate task. Additionally, A+ fathers had more negative amplitudes for a late slow wave in both tasks, suggesting electrophysiological consequences of long-term alcohol abuse.     

Recruitment of healthy participants for studies on risks for alcoholism: effectiveness of random digit dialling

AIMS: To compare the effectiveness of two strategies for recruiting healthy research volunteers. METHODS: Demographic characteristics and recruitment costs of participants who completed a laboratory study examining risk factors for alcoholism recruited through random digit dialling (N = 11) and community advertisements (N = 102) were compared. RESULTS: Advertisement yielded a more representative sample [76% Caucasian, less well educated (M = 15.2 years, SEM = 0.2; P < 0.05), more equally divided by family history of alcoholism (43% FH- and 57% FH+), and lower in SES (M = 42.8, SEM = 1.3; P < 0.05)] and was more cost effective (72 dollars vs 2272 dollars per participant) than random digit dialling. CONCLUSIONS: Findings are relevant to alcohol researchers trying to determine the recruitment strategy that will yield the most representative sample at the lowest cost.     

Autonomic reactivity to mental stressors after single administration of lorazepam in male alcoholics and healthy controls

Clinically unaffected sons of male alcoholics differ from controls without a family history of alcoholism in two respects: increased autonomic reactivity to aversive as well as non-aversive stimuli and increased attenuation of these responses by alcohol. This pattern of autonomic hyper-reactivity and alcohol-induced stress response dampening (SRD) might be a trait marker of genetic vulnerability and is often interpreted in terms of a diathesis stress model of alcohol dependence. Forty-five alcohol-dependent men (mean age: 39.20 years) and 37 healthy controls (mean age: 35.03 years) participated in a double-blind cross-over study in two experimental sessions each. The benzodiazepine lorazepam was selected as an alcohol substitute. Autonomic reactivity and lorazepam-induced SRD were assessed during incentive and non-incentive reaction time tasks as well as mental arithmetics. Alcohol-dependent men showed elevated resting heart rate levels and increased number of non-specific electrodermal responses. Evidence for autonomic hyper-reactivity was found for a subgroup of alcoholics with a family history of alcoholism.     

Alcohol and alcoholism among Brazilian adolescent public-school students

OBJECTIVE: To estimate the prevalence of alcohol consumption and alcoholism among working and non-working adolescents. METHODS: Cross-sectional study with a systematic, stratified sample 993 working adolescents and 1,725 non-working adolescents. The study included students enrolled in 1998 in the state public network schools of a city in Center-Western Brazil. An anonymous, self-administered questionnaire was completed by subjects in the classroom. Univariate and bivariate analyses and logistic regression were used. RESULTS: We found prevalences of 71.3% for alcohol consumption and 13.4% for alcoholism in the total sample, and higher prevalences among working students (81.0% and 14.9%) than among non-workers (65.8% and 12.6%). In addition to the association between alcohol use and work, we found both differences and similarities between the two groups. Alcoholism is not associated with work but is associated with male sex (OR=1.61; 95% CI: 1.18-2.19) and family history of alcohol use among both non-workers (OR=2.19; 95% CI: 1.60-2.99) and workers (OR=2.10; 95% CI: 1.42-3.12). CONCLUSIONS: The results of the present study indicate a high prevalence of alcohol consumption and alcoholism, which is higher among working adolescents. Sociodemographic, family, and work-related factors must be considered when attempting to implement educational measures aimed at changing alcohol-related behaviors in this population.     

Alcohol consumption,family history of hematolymphoproliferative cancer,and the risk of non-Hodgkin's lymphoma in men

PURPOSE: To investigate the association between alcohol consumption and the risk of non-Hodgkin's lymphoma (NHL) and to examine whether the association is modified by a family history of hematolymphoproliferative cancer (HLPC). METHODS: Data on white men from two population-based case-control studies of NHL conducted in Iowa/Minnesota and Kansas were pooled for this analysis. Information on alcohol consumption, family history of HLPC, and other factors was obtained by interviewing 792 cases and 2193 controls or, if deceased, their next-of-kin. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There was no clear association between NHL and the use of alcohol, beer, hard liquor, or wine. The relationship, however, may differ according to a family history of HLPC. Alcohol use was not associated with the risk of NHL in men without a family history of HLPC (ORs = 0.8 and 0.9 for men consuming alcohol < or = median and > median, respectively), the presence of a family history in the absence of alcohol use was associated with a slightly increased risk (OR = 1.4; 95% CI 0.8-2.5), whereas risks of NHL among men with a positive family history were 2.1 (CI 1.0-4.7) for men consuming alcohol < or = median (13.7 g/day) and 2.8 (1.3-5.9) for men consuming alcohol greater than median. CONCLUSIONS: The present data found no clear association between alcohol consumption and the risk of NHL among men without a family history of HLPC, whereas alcohol intake was associated an elevated risk in men with a positive family history. The finding of effect modification of the alcohol-NHL association by a family history of HLPC is novel and requires confirmation.     

Health policy and genetic endowments: Understanding sources of response to Minimum Legal Drinking Age laws

This paper uses policy‐induced variation in legal access to alcohol in the United States to explore interactions between genetic predispositions and health behaviors. It is well known that Minimum Legal Drinking Age (MLDA) laws have discrete impacts on binge drinking behaviors, but less is known about heterogeneity of the effects and the characteristics of individuals most and least affected. Using the Add Health data, this paper explores differential policy effects based on polygenic scores (PGS), which are genome‐wide summary measures predicting health outcomes. Specifically, we leverage PGS for alcoholism and for a broader set of risk‐taking behaviors to explore heterogeneities in response to the policy and consider mechanisms for the responses. Like previous literature using the Add Health and other datasets, we find main effects of MLDA in increasing recent binge drinking episodes by approximately 5 percentage points. We find MLDA effects are concentrated entirely in individuals with high PGS for alcohol use. We are also able to compare these results with measures of parental alcoholism as a global proxy for family history.