Self-reported subjective perception of intoxication reflects family history of alcoholism when breath alcohol levels are constant

BACKGROUND: The premise of this study is that the increased familial risk for alcoholism is associated with genetic determinants of the response to alcohol, characterized by sensitivity and adaptation. Following a single administration, sensitivity is the initial response to alcohol, expressed as the change in dependent measures from baseline. Adaptation of dependent measures within a single exposure to alcohol can be expressed as acute tolerance (recovery of dependent measures toward baseline values) or sensitization (movement of dependent measure further away from baseline values). This study tested the hypothesis that family history-positive (FHP) subjects are more sensitive and more adaptive to alcohol compared with family history-negative (FHN) subjects. METHODS: The initial response and development of adaptation to alcohol were assessed by using self-reported subjective perceptions during a breath alcohol concentration (BrAC) clamp of 60 mg%. The Biphasic Alcohol Effects Scale, the Sensation Scale and a visual analog scale of intoxication were acquired at baseline, after the BrAC clamp was established, and after maintenance of the clamp for 105 min. RESULTS: FHP subjects were more sensitive to alcohol compared with FHNs, as evidenced by greater changes in feelings of intoxication when the BrAC clamp was initially achieved. While the clamp was maintained, the FHP subjects adapted to the effects of alcohol and their perceptions of intoxication became indistinguishable from those of the FHN subjects. The FHP subjects had developed acute tolerance to alcohol, whereas the FHN subjects did not. Other self-reported perceptions of alcohol's effects did not distinguish between the groups. CONCLUSIONS: A differential family history of alcoholism was reflected in self-reported subjective perceptions of intoxication when the brain's exposure to a specified concentration of alcohol was held constant (BrAC of 60 mg%). FHP subjects reported greater intoxication after alcohol and subsequently developed acute tolerance to alcohol compared with FHN subjects.     

Density of familial alcoholism and its effects on alcohol use and problems in college students

Background:  Previous studies of family history of alcoholism (FHA) in college students have typically relied on dichotomous indices of paternal drinking. This study examined the prevalence of FHA and its effects on alcohol use and problems using a density measure in a sample ( n  =   408) of college students.
Methods:  Undergraduate students completed an anonymous survey in exchange for course credit. Data was collected between 2005 and 2006.
Results:  Using a density measure of FHA, we observed an overall prevalence rate of 65.9% and a rate of 29.1% for FHA in both first and second-degree relatives. Structural equation modeling (SEM) was used to investigate relations among FHA, alcohol use/problems and previously identified etiological risk factors for alcohol use disorders (AUD). Results indicated a significant positive association between FHA and alcohol-related problems and this relationship was mediated by age of onset of drinking, behavioral undercontrol and current cigarette use. Behavioral undercontrol also mediated the relationship between gender and alcohol problems. Additionally, FHA was associated with an earlier age of onset of drinking and this was related to greater alcohol use.
Conclusions:  Assessing density of FHA in future trajectory research may capture a greater number of students at risk for acute alcohol-related problems and/or future development of AUDs. Future preventive interventions with this population, which should begin well before the college years, may benefit from considering personality factors and incorporating smoking cessation to help identify at-risk students and assist those who wish to cut down on their alcohol use but find that smoking acts as a trigger for increased drinking.     

Saccadic eye movements are associated with a family history of alcoholism at baseline and after exposure to alcohol

OBJECTIVE: To evaluate the influence of family history of alcoholism (FHA) on the response of saccadic eye movements to alcohol. METHOD: Saccadic performance was evaluated in 54 healthy adult subjects with a FHA (family history-positive) and 49 controls (family history-negative). Alcohol and placebo sessions were presented in counterbalanced order. Alcohol was administered intravenously to achieve and maintain a target breath alcohol concentration of 60 mg/100 ml (60%) for 160 min in each subject. During each session, saccadic eye movement testing was performed at baseline (before infusion of alcohol) and twice during the steady-state target breath alcohol concentration. The saccadic testing elicited visually guided saccades (VGS) and antisaccades (AS). Saccadic latency and velocity and the percentage of AS errors were quantified and analyzed using multivariate analysis of variance. RESULTS: The family history-positive and family history-negative groups showed an overall difference at baseline in AS and VGS latencies and velocities in the alcohol and placebo sessions ( p= 0.006). Alcohol delayed saccades such that AS and VGS latencies increased (p = 0.0001) and slowed the execution of saccades such that peak velocities decreased ( p = 0.0002). The percentage of AS errors decreased after alcohol administration, but no significant effect of alcohol (alcohol versus placebo session) was observed (p = 0.1). Latency of AS saccades demonstrated a significant overall FHA effect (p = 0.02) and a significant interaction between FHA and response to alcohol over time (p = 0.02). CONCLUSIONS: Differences in operational characteristics of the saccadic control system are associated with FHA in adult social drinkers, both at baseline and when the brain is exposed to ethanol at 60 mg/100 ml.     

Effects of stress and alcohol on subjective state in humans

BACKGROUND: There is increasing evidence that stress and hypothalamic-pituitary-adrenal axis activation interact with drugs of abuse and influence drug-taking behaviors. Both studies with laboratory animals and survey data with alcohol users suggest that acute or chronic stressful events increase alcohol intake. One mechanism for the increase in alcohol intake may be that stress alters the subjective effects produced by the drug in ways that enhance the reinforcing properties of alcohol. Therefore, in this study we determined whether an acute social stressor alters subjective responses to ethanol in humans. The stressor was a modified version of the Trier Social Stress Test, an arithmetic task that increases cortisol levels. METHODS: Twenty male volunteers participated in two laboratory sessions, in which they performed the Trier Social Stress Test on one session and no task on the other session, immediately before consuming a beverage that contained ethanol (0.8 g/kg in juice) or placebo (juice alone). Eleven subjects received ethanol on both sessions, and nine subjects received placebo on both sessions. Primary dependent measures were self-report questionnaires of mood states. Salivary levels of cortisol were obtained to confirm the effectiveness of the stress procedure. RESULTS: Stress alone produced stimulant-like subjective effects. In the group who received ethanol, stress increased sedative-like effects and decreased stimulant-like effects. CONCLUSIONS: At this relatively high dose of ethanol, stress increased sedative effects of alcohol and did not increase desire for more alcohol. It is possible that in some individuals, the increased sedative effects after stress may increase the likelihood of consuming more alcohol. The effects of stress on consumption at this, or lower, doses of alcohol remain to be determined.     

Sleep following alcohol intoxication in healthy, young adults: effects of sex and family history of alcoholism

Background: This study evaluated sex and family history of alcoholism as moderators of subjective ratings of sleepiness/sleep quality and polysomnography (PSG) following alcohol intoxication in healthy, young adults. Methods: Ninety‐three healthy adults [mean age 24.4 ± 2.7 years, 59 women, 29 subjects with a positive family history of alcoholism (FH+)] were recruited. After screening PSG, participants consumed alcohol (sex/weight adjusted dosing) to intoxication [peak breath alcohol concentration (BrAC) of 0.11 ± 0.01 g% for men and women] or matching placebo between 20:30 and 22:00 hours. Sleep was monitored using PSG between 23:00 and 07:00 hours. Participants completed the Stanford Sleepiness Scale and Karolinska Sleepiness Scale at bedtime and on awakening and a validated post‐sleep questionnaire. Results: Following alcohol, total sleep time, sleep efficiency, nighttime awakenings, and wake after sleep onset were more disrupted in women than men, with no differences by family history status. Alcohol reduced sleep onset latency, sleep efficiency, and rapid eye movement sleep while increasing wakefulness and slow wave sleep across the entire night compared with placebo. Alcohol also generally increased sleep consolidation in the first half of the night, but decreased it during the second half. Sleepiness ratings were higher following alcohol, particularly in women at bedtime. Morning sleep quality ratings were lower following alcohol than placebo. Conclusions: Alcohol intoxication increases subjective sleepiness and disrupts sleep objectively more in healthy women than in men, with no differences evident by family history of alcoholism status. Evaluating moderators of alcohol effects on sleep may provide insight into the role of sleep in problem drinking.     

Striatal dopamine release and family history of alcoholism

BACKGROUND: The offspring of alcohol-dependent individuals are at increased risk for alcoholism. The present study was designed to determine whether mesolimbic dopamine binding potential (BP), dopamine release, stress hormones, and subjective responses to intravenous amphetamine are different in nonalcoholic offspring from families with a history of alcohol dependence [family history positive (FHP)] than in nonalcoholic offspring without a family history of alcohol dependence [family history negative (FHN)]. METHODS: Participants were 41 healthy men and women (11 FHP, 30 FHN; age range 18-29). After completing baseline psychiatric symptom and personality measures, striatal D2/D3 dopamine BP and dopamine release in response to an amphetamine challenge were measured with positron emission tomography (PET) using the D2/D3 dopamine (DA) receptor radioligand [11C]raclopride. Binding potential was defined as Bmax/KD, percent change in BP from baseline defined dopamine release. During the scans, subjects rated the degree to which they were experiencing each of 10 possible drug effects. Plasma cortisol and growth hormone (GH) were also measured at scheduled intervals during the scans. RESULTS: Neither baseline BP nor dopamine release differed by family history. Similarly, subjective responses to amphetamine did not differ by a family history of alcoholism. Although both cortisol and GH increased following administration of amphetamine, these increases did not differ between family history groups. CONCLUSIONS: Using amphetamine to provoke mesolimbic dopamine, we did not show significant differences in dopamine release, subjective responses, or stress hormone measures as a function of family history of alcoholism.     

Altered emotion-modulated startle in young adults with a family history of alcoholism

BACKGROUND: Alcoholism risk may be accompanied by poor regulation of emotions, signaling altered central nervous system processes. This study used the emotion-modulated startle paradigm to test the hypothesis that young adults with a positive paternal history of alcoholism (FH+), relative to family-history-negative persons (FH-), have altered emotional reactivity to environmental cues. METHODS: We tested 30 FH+ and 30 FH-, 15 males and 15 females in each group. Participants completed self-report instruments and interviews and had eye blink electromyograms (EMG) measured to acoustic startle probes while viewing color photographs rated as affectively pleasant, neutral, and unpleasant. RESULTS: FH- had the expected linear increase in startle magnitude, with eye blink EMG gaining in strength (F = 18, p < 0.0002) from pleasant to neutral to unpleasant slides. In contrast, FH+ did not show EMG potentiation to the unpleasant slides and therefore lacked the same linear trend (F < 1, p > 0.4). Notably, FH groups rated the emotional valence and arousal of the photographs in similar ways. Self-reported negative affect partly accounted for the lack of startle potentiation in FH+, suggesting that startle modulation differences between the groups may be associated with underlying psychological characteristics. CONCLUSIONS: These findings implicate altered limbic outputs to the startle pathway in FH+ despite normal conscious evaluation of emotional arousal and pleasantness of the slides. This method may provide a useful paradigm for testing processing of emotionally relevant stimuli in relation to risk for alcohol use disorders.     

Mecamylamine attenuates the subjective stimulant-like effects of alcohol in social drinkers

BACKGROUND: Recent studies have implicated central nicotinic cholinergic receptor systems in the reinforcing properties of alcohol. In laboratory animals, mecamylamine, a central nicotinic receptor antagonist, reduces the consumption of and preference for alcohol. This study investigated the effect of mecamylamine on the subjective responses to alcohol in humans. It was hypothesized that mecamylamine (7.5 and 15 mg) would attenuate the stimulant-like subjective effects of alcohol (0.8 g/kg) and decrease the self-reported desire to consume additional alcohol beverages. METHODS: Fourteen male and 13 female nonsmokers participated in 6 laboratory sessions. During each session, subjects received, in randomized order under double-blinded conditions, a capsule containing mecamylamine (7.5 or 15 mg) or placebo followed by a beverage containing alcohol (0.8 g/kg) or placebo. Physiologic and subjective-effect measures were taken at 30-min intervals for 2 hr after beverage consumption. RESULTS: Mecamylamine attenuated the stimulant and euphoric effects of alcohol and reduced the self-reported desire to consume additional alcohol beverages. This effect was most pronounced in men, even though women exhibited greater physiologic reactions to mecamylamine. CONCLUSIONS: These findings suggest that nicotinic cholinergic receptors are involved in mediating some of the stimulant-like effects of alcohol.     

Adult transition from at-risk drinking to alcohol dependence: the relationship of family history and drinking motives

Background:  Prospective studies have not previously examined whether a family history of alcoholism and drinking motives conjointly predict a diagnosed DSM-IV alcohol abuse or dependence in adults, despite a large literature that each is associated with alcohol consumption. The focus of this study is the conjoint, prospective examination of these risk factors in a 10-year longitudinal study of adults who were at-risk drinkers at baseline.
Methods:  Prospective, population-based cohort of drinkers aged 18 or older from a Northeastern U.S. area initially evaluated for history of alcohol use disorders and drinking motives in 1991 to 1992. New onset dependence was studied in those who never met the criteria for alcohol dependence at baseline ( n  = 423), and new onset abuse was studied in those who never met the criteria for alcohol abuse at baseline ( n  = 301) and who did not develop dependence during the follow-up.
Results:  Family history significantly interacted with 2 baseline drinking motives in predicting new onsets of DSM-IV alcohol dependence: drinking to reduce negative affect (OR 3.38; 95% CI 1.05, 10.9) and drinking for social facilitation (OR 3.88; CI 1.21, 12.5). Effects were stronger after conditioning the drinking motives on having a positive family history of alcoholism. In contrast, in predicting new onsets of alcohol abuse, drinking motives did not have direct effects or interact with family history.
Conclusions:  Those who drank to reduce negative affect or for social facilitation at baseline were at greater risk of alcohol dependence 10 years later if they also had a family history of alcoholism. These results suggest an at-risk group that can be identified prior to the development of alcohol dependence. Further, the findings suggest utility in investigating the interaction of drinking motives with measured genetic polymorphisms in predicting alcohol dependence.     

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.     

Effects of aripiprazole on subjective and physiological responses to alcohol

Background:  Aripiprazole is an atypical antipsychotic with partial agonist activity at D₂ receptors, which could reduce the reinforcing effects of alcohol. The present study examined whether aripiprazole modifies the behavioral and physiological effects of a moderate dose of alcohol in a group of social drinkers.
Methods:  Eighteen healthy subjects (9 men; mean age = 27.6 years) completed a double-blind, within-subject study with 3 experimental sessions in a randomized sequence, during which they received no medication, aripiprazole 2.5 mg, or aripiprazole 10 mg on the day prior to the laboratory session. During the session, subjects consumed alcohol that was served as three standardized drinks (i.e., a total of 0.8 g/kg for men and 0.7 g/kg for women). Breath alcohol concentration (BrAC), heart rate, blood pressure, static ataxia, and subjective effects were measured regularly throughout the laboratory sessions.
Results:  Alcohol consumption produced physiological and subjective responses that were consistent with the literature on its effects. Pre-treatment with aripiprazole was generally well tolerated, with tiredness being the most commonly reported adverse event. The medication was associated with modest physiological effects. It also significantly and dose-dependently increased the sedative effects of alcohol and, to a lesser degree, decreased the euphoric effects of alcohol.
Conclusions:  These findings require replication in a larger subject sample that includes heavy drinkers and in a study that employs a placebo session. Based on its capacity to increase the sedative effects and decrease the euphoric effects of alcohol, aripiprazole could be of value in the treatment of heavy drinking.     

Lateral asymmetries in the frontal brain: effects of depression and a family history of alcoholism in female adolescents

BACKGROUND: Subtle electroencephalographic (EEG) abnormalities have been detected among subjects with depressed affect. The present study attempted to discern whether these abnormalities reflect a main effect or an interaction between depression and either of two family history variables--a family history of alcoholism or a family history of depression. METHODS: The subjects were 151 adolescent females, aged 14 to 20 years, of whom 58 met DSM-III-R diagnostic criteria for a lifetime history of a major depressive episode. The electroencephalogram was recorded from 31 electrode sites while the subjects sat relaxed, with their eyes open, for 5 min. RESULTS: Analyses of EEG data revealed that a personal history of depression and a family history of alcoholism had opposite effects on the EEG power spectrum. Depression was associated with an increase in alpha power (7.5-12.5 Hz). In contrast, a family history of alcoholism was associated with an increase in fast beta power (19-30 Hz) and a decrease in theta power (4-7 Hz). There were no significant main or interactive effects of a family history of depression. Current source density topographic analyses of the significant group differences in alpha and fast beta power demonstrated that the effects of depression could be localized to the right frontal brain, whereas the effects of a family history of alcoholism were localized to the left frontal area. CONCLUSIONS: The laterally opposite effects of depression and a family history of alcoholism suggest a high level of functional differentiation of the frontal brain. They also suggest that the different neurophysiological substrates of depression and familial risk can be distinguished through the use of modern methods of EEG source localization.     

Effects of cigarette smoking and family history of alcoholism on sweet taste perception and food cravings in women

BACKGROUND: Despite popular beliefs that smoking affects the sensitivity and liking of sweet-tasting foods and beverages, few psychophysical studies have examined this phenomenon and none have taken into account the individual's family history of alcoholism (FH+), a predictor of heightened sweet preferences. METHODS: A within- and between-subjects study was conducted to determine the effect of both cigarette smoking and an acute exposure to nicotine on sweet taste sensitivity and preferences in women. Two groups were studied on 2 days separated by 1 week: women who were current smokers (n = 27, 18 were FH+) and those who never smoked in their lifetime (n = 22, 9 were FH+). Current smokers smoked nicotine-containing cigarettes during 1 test session and nicotine-free cigarettes during the other. The procedures were identical during both test sessions for the group of never smokers, with the exception that they did not smoke. Two-alternative staircase methods and forced-choice tracking procedures were used to assess sucrose thresholds and preferences, respectively, during both test session. Standardized questionnaires were administered to assess food cravings as well as smoking and alcohol usage and dependence. The Family Interview for Genetic Studies was used to detect alcoholism according to the DSM III criteria for family members up to second-degree relatives. RESULTS: Acute exposure to nicotine did not affect sucrose detection thresholds or preferences, but smokers had significantly higher sucrose detection thresholds than never smokers. The greater the smoking dose in pack-years, the lower the sucrose sensitivity. Regardless of smoking status, women who were FH+ preferred significantly higher sucrose concentrations and craved sweets more often than women who were not. CONCLUSIONS: Both smoking and having a family history of alcoholism had differential effects on sweet taste. Smoking was associated with decreased sweet taste sensitivity whereas having a family history of alcoholism was associated with heightened sweet preferences. These findings suggests that future research on the effects of smoking on food habits and cravings should take into account family history of alcoholism given its association with sweet liking and the increased likelihood to develop a tobacco disorder.     

Subjective responses to alcohol: a paradigm shift may be brewing

Background: The meta‐analysis by Quinn and Fromme (2011 ) is reviewed and integrated into the larger field. Guidelines for future research are presented. Results: With results of the meta‐analysis along with those of a recent comprehensive prospective study by our group ( King et al., 2011 ), there is a call to the field to specify terms and integrate theoretical frameworks to advance our knowledge and improve comparisons across trials. Conclusions: The meta‐analysis is both timely and thorough and will provide clinical researchers with important information to move the field forward.     

Impulsive errors on a Go-NoGo reaction time task: disinhibitory traits in relation to a family history of alcoholism

Background:  Behavioral undercontrol may contribute to risk for alcoholism in vulnerable persons. We predicted that healthy young adults with a family history of alcoholism (FH+) who also displayed externalizing behavior characteristics (low scores on the California Psychological Inventory Sociability Scale; CPI-So) would exhibit more impulsive responding (false alarms) on a Go-NoGo reaction time task.
Methods:  Subjects were 230 healthy volunteers, 18 to 30 years of age with no history of alcohol or drug dependence. The task included 100 trials: 60 of "Go," calling for a button press, and 40 of "NoGo," or "XX," calling for inhibiting a response. Data analysis involved a signal detection analysis of performance with subsequent group comparisons for rates of impulsive responding indicated by False Alarms (responses to NoGo signals).
Results:  CPI-So scores were lower in FH+ than in FH– ( p  < .000001) indicating a greater clustering of disinhibitory tendencies in these persons. FH, CPI-So scores, and Gender together predicted false alarm rates, accounting for 4.9% of the variance, F  =   3.89, p  = 0.009. False alarms were associated with low CPI-So scores, F  =   5.15, p  = 0.024, and being male, F  =   6.27, p  = 0.013, but not with FH once these variables were accounted for.
Conclusions:  A disinhibited temperament may underlie a behavioral impulsivity that contributes to elevated risk for future alcoholism, especially among FH+ males.     

Working memory and decision-making biases in young adults with a family history of alcoholism: studies from the Oklahoma family health patterns project

BACKGROUND: Alcohol misuse is more common in persons with a family history of alcoholism (FH+) than in those with no such history (FH-). Among FH+, behavioral disinhibition and male sex seem to signal the presence of an increased risk. METHODS: This study examined cognitive and behavioral characteristics of 175 nonabusing 18- to 30-year-olds, 87 FH+ and 88 FH-, who were further characterized by their degree of behavioral disinhibition using the Sociability scale of the California Personality Inventory. Working memory and decision making were tested using the Stroop Color-Word Test and the Iowa Gambling Task, a simulated card game. RESULTS: Persons with a family history of alcoholism who were behaviorally disinhibited displayed significantly greater interference on the Stroop task than the other subgroups. On the Iowa Gambling Task, FH+ males, but not the females, were significantly more attentive to financial gains than other subgroups, and they had greater consistency in their choice behaviors. CONCLUSIONS: Persons with a family history of alcoholism, in combination with behavioral disinhibition, appears to signal working memory deficits and in combination with male sex indicates an attraction to the rewarding aspects of a risk-taking challenge. These findings are not secondary to heavy exposure to alcohol or other drugs, but instead reflect intrinsic risk-related familial and personal characteristics of the subjects.     

The alcohol clamp: applications, challenges, and new directions--an RSA 2004 symposium summary

This article summarizes the proceedings of a symposium organized and cochaired by Vijay Ramchandani and Sean O'Connor and presented at the 2004 Research Society on Alcoholism meeting in Vancouver, BC, Canada. The objectives of this symposium were: (1) to provide a rationale for the development and use of the alcohol clamp and the requirements for its use in alcohol challenge studies; (2) to highlight recent studies conducted using the alcohol clamp to identify sources of variation in the pharmacokinetics and pharmacodynamics of alcohol, as well as to address important research questions related to the relationship between the response to alcohol and the risk for alcoholism; and (3) to provide a perspective on progress, address limitations of the clamp, and identify new directions for alcohol challenge research. The symposium began with an introduction and overview of the alcohol clamp, by Vijay Ramchandani. This was followed by 4 presentations that highlighted recent studies conducted using the clamp including: (1) determination of the influence of alcohol dehydrogenase polymorphisms on alcohol elimination rates in a male Jewish population, by Yehuda Neumark; (2) examination of family history of alcoholism, recent drinking history, and levels and rates of administration as determinants of the response to alcohol and risk for alcoholism, by Sean O'Connor; (3) evaluation of the time course of ethanol intoxication on neuroendocrine function in humans, by Ulrich Zimmermann; and (4) a study of the effects of steady-state blood alcohol levels on auditory event-related potentials in rats, by Sandra Morzorati. Harriet de Wit summarized and discussed the research presented at the symposium and provided her perspective on future directions for research using the alcohol clamp.     

Course of DSM-IV alcohol dependence in a community sample: effects of parental history and binge drinking

BACKGROUND: The role of positive family history in the etiology of alcohol dependence has been demonstrated repeatedly but little is known about the effect of this risk factor on the chronicity of alcohol dependence once it has begun. METHODS: We studied the effects of parental and sibling history in conjunction with frequency of binge drinking in a sample of 169 community residents who met criteria for DSM-IV alcohol dependence at the baseline interview. Subjects were re-interviewed approximately 1 year later and the status of their alcohol-dependence disorders (remitted or chronic) was determined. RESULTS: Parental history of alcoholism was significantly related to chronicity of alcohol dependence, as was frequency of binge drinking. CONCLUSIONS: Failure to find an effect for family history on chronicity would have suggested that the effect was transient, perhaps interacting with time-limited environmental vulnerability. The finding of a positive relationship between family history and chronicity suggests that the relationship between familial/ genetic background and alcohol dependence is stable.     

Effects of family history of alcohol use disorders on spatial working memory BOLD response in adolescents

Background:  A positive family history (FH) of alcohol use disorders (AUD) has been linked to increased risk for the development of AUD, and neurocognitive factors have been postulated as important underlying mechanisms of familial alcoholism transmission.
Methods:  We used functional magnetic resonance imaging (fMRI) during a spatial working memory (SWM) and vigilance paradigm to investigate potential neurodevelopmental differences linked to familial density of AUD in 72 adolescents aged 12 to 14 years.
Results:  Youth with denser family histories of AUD showed less activation during a simple vigilance condition relative to SWM in cingulate and medial frontal gyri (β = 0.28, p  = 0.03), and a trend for more relative activity during rest (β = −0.25, p  = 0.07) in this cluster.
Conclusions:  Youth with greater familial densities of AUD may be less successful at modulating activity of the default network, potentially indicating a greater propensity for task-independent thought or reduced inhibition of task-irrelevant processing. Failure to moderate activation of the default network may have implications for cognitive efficiency and goal directed behavior in youth with dense FH. Further, aberrant activation in cingulate regions may be linked to genetic variation in GABA receptor units, suggesting a useful endophenotype for risk associated with alcohol dependence.