Impaired eyeblink conditioning in children with fetal alcohol syndrome

Background: Eyeblink conditioning (EBC) is a Pavlovian paradigm that involves contingent temporal pairing of a conditioned stimulus (e.g., tone) with an unconditioned stimulus (e.g., air puff). Animal studies have shown that binge consumption of alcohol during pregnancy impairs EBC and that this impairment is likely mediated by a loss of neurons in the inferior olive and the cerebellar cortex and deep nuclei, as well as by a reduction in neural plasticity in the cerebellar deep nuclei. Methods: Short delay EBC was examined in 98 5‐year‐old children born to women from the Coloured (mixed ancestry) community in Cape Town, South Africa, who were recruited prenatally and are participating in the first prospective longitudinal study of children with fetal alcohol syndrome (FAS). FAS status was assessed at 5 years by expert dysmorphologists. Two sessions of 50 trials each were administered to the children; a third session was administered the following day to those children who did not meet criterion of 40% conditioned responses in session 2. Results: Not a single child with FAS met criterion for conditioning as contrasted with 75.0% of the controls. Whereas 86.7% of the controls who were conditioned met criterion by the end of Session 2, a large proportion of the relatively few alcohol‐exposed nonsyndromal children who conditioned did not do so until Session 3. These alcohol effects on EBC persisted after controlling for IQ. Three of 4 microcephalic children who were not exposed to alcohol were successfully conditioned. Conclusions: This is the first prospective study to demonstrate impaired EBC in children diagnosed with FAS. Successful EBC in a microcephalic group supports the inference that the EBC deficit is specific to prenatal alcohol exposure and a potential biomarker for diagnosis of exposed children lacking the distinctive FAS dysmorphology. Delay EBC has a high sensitivity for identifying individuals with a diagnosis of probable FAS.     

Nursing experiences with an alcohol-intoxicated rat dam counteract appetitive conditioned responses toward alcohol

BACKGROUND: Infant rats detect small amounts of alcohol (175 mg%) that are present in maternal milk whenever the dam is moderately intoxicated with alcohol. Interaction with an alcohol-intoxicated mother during the first 2 weeks of life facilitates the preweanling's subsequent discrimination of alcohol's orosensory attributes and produces conditioned aversion to alcohol. The present study further analyzed the hedonic content of infantile alcohol memories established in the nursing context by testing the interaction between experiences with an alcohol-intoxicated dam and learning procedures aimed at establishing an appetitive conditioned response toward alcohol. METHODS: Experiment 1 was to determine appropriate parameters to establish a reliable conditioned preference for alcohol in 16-day-old infants. For conditioning, intraorally infused sucrose solution (appetitive reinforcer) was paired with alcohol's orosensory cues derived from an acute state of alcohol intoxication (3 g/kg). Two control groups included an unpaired condition and a group given sucrose after water intubation. Infants then were evaluated in an alcohol intake test. Relative to control animals, a reliable conditioned preference for alcohol was registered in paired pups. In experiment 2, these conditioning procedures were applied to infant rats which, before conditioning, suckled from dams subjected to a 2.5 g/kg alcohol dose (intragastric) or from water-treated females during postpartum days 3, 5, 7, 9, 11, and 13. RESULTS: Experiment 2 showed that maternal treatment significantly affected the establishment of conditioned preferences for alcohol. Whereas pups reared by control dams exhibited reliable appetitive conditioning to alcohol, infants raised by alcohol dams completely failed to develop appetitive conditioning. CONCLUSIONS: The present results suggest that alcohol-related memories generated via infantile interactions with an intoxicated dam counteract subsequent conditioning of alcohol ingestion. In conjunction with prior studies, it is concluded that alcohol-related nursing experiences are capable of promoting alcohol memories with a negative hedonic content.     

The association between alcohol consumption patterns and adherence to food consumption guidelines

Objective: To examine the association between alcohol consumption patterns and adherence to major food consumption guidelines in adults in Spain. Methods: Telephone survey of 12,037 persons, representative of the population age 18 to 64 years in the region of Madrid, conducted from 2000 to 2005. The threshold between average moderate and excessive drinking was 40 g alcohol/d in men and 24 g/d in women. Binge drinking was defined as intake of ≥80 g alcohol in men and ≥60 g in women during 1 drinking session in the last 30 days. Food consumption was measured with a 24‐hour recall. Statistical analyses were performed using logistic regression and adjusted for the main confounders. Results: In total, 4.3% of study participants were excessive drinkers and 10.3% binge drinkers; 6.5% preferred spirits and 24.2% drank with meals. In comparison with never drinking, average moderate drinking with binge drinking was associated with excessive meat consumption (>1 serving/d). Excessive alcohol consumption without binge drinking was associated with insufficient intake of milk products (<2 servings/d) and excessive consumption of meat, fish, and eggs (>2 servings/d). Excessive drinkers with binge drinking more often did not meet the guidelines on consumption of fruit and vegetables (<3 servings/d), milk products, and meat. Excessive drinkers, with and without binge drinking, were more likely to skip a meal, especially breakfast. Consumption mainly of spirits was associated with insufficient fruit and vegetable consumption, and with skipping a meal. Finally, drinking at mealtimes was associated with poor adherence to most of the food consumption guidelines. No dietary differences between men and women were found in relation to alcohol consumption. Conclusions: Average excessive alcohol consumption, binge drinking, preference for spirits, and drinking alcohol at mealtimes are associated with poor adherence to major food consumption guidelines.     

Cardiovascular Consequences of Binge Drinking: An Integrative Review with Implications for Advocacy,Policy, and Research

Worldwide, binge drinking is a major public health problem. The popularized health risks associated with binge drinking include physical injury and motor vehicle crashes; less attention has been given to the negative effects on the cardiovascular (CV) system. The primary aims of this review were to provide a summary of the adverse effects of binge drinking on the risk and development of CV disease and to review potential pathophysiologic mechanisms. Using specific inclusion criteria, an integrative review was conducted that included data from human experimental, prospective cross‐sectional, and cohort epidemiological studies that examined the association between binge drinking and CV conditions such as hypertension (HTN), myocardial infarction (MI), stroke, and arrhythmias. Studies were identified that examined the relationship between binge drinking and CV outcomes. Collectively, findings support that binge drinking is associated with a higher risk of pre‐HTN, HTN, MI, and stroke in middle‐aged and older adults. Binge drinking may also have adverse CV effects in young adults (aged 18 to 30). Mechanisms remain incompletely understood; however, available evidence suggests that binge drinking may induce oxidative stress and vascular injury and be proatherogenic. Public health messages regarding binge drinking need to include the effects of binge drinking on the CV system.     

A characterization of approach and avoidance learning in high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats

Background: This study was undertaken as one of a series of experiments designed to examine basic behavioral characteristics present in rats bred specifically for alcohol preference. The basic premise for these experiments has been the idea that alcohol‐preferring and ‐nonpreferring rats may differ in basic activation and inhibition control mechanisms that govern behavior and that different lines of alcohol‐preferring rats may demonstrate differential deficits in behavioral activation and behavioral inhibition tendencies. In the present experiment, conditioned approach and avoidance behaviors were studied in alcohol‐naïve high–alcohol‐drinking (HAD), low–alcohol‐drinking (LAD), and N/NIH rats to evaluate behavioral activation in this line of rats. Methods: High alcohol drinking (HAD1), low alcohol drinking (LAD1), and N/Nih stock rats were trained to press a response bar during a tone signal to avoid a mild foot shock or receive a food reward. In addition, HAD2 and LAD2 rats, independently‐bred replicate lines of the HAD1/LAD1 rats, were trained on the avoidance task. Results: Although the HAD1 rats easily learned the appetitive version of the bar‐pressing task, they did not learn the avoidance response. The LAD1 and N/Nih rats learned both the approach and the avoidance tasks normally. Similar to HAD1 rats, the HAD2 rats did not learn the avoidance response whereas LAD2 rats showed significant avoidance performance levels. Conclusions: The present data demonstrated that both HAD1 and HAD2 rats had a rather specific behavioral activation deficit: although they easily learned to press a bar to receive food reinforcement, they did not learn to press the bar to avoid a foot shock. We speculate that this failure to learn the avoidance response may be related to heightened anxiety in the HAD rats and that this excessive anxiety may lead to the development of high levels of alcohol consumption in these selectively bred rats.     

Item response theory analysis of binge drinking and its relationship to lifetime alcohol use disorder symptom severity in an American Indian community sample

Background: Item response theory (IRT) has been used to examine alcohol use disorder (AUD) symptoms and their psychometric properties but has not been previously applied to AUD symptoms from an American Indian sample. Methods: Lifetime DSM‐IV AUD symptoms and binge drinking (5+ drinks men/4+ drinks women) at ≥1, ≥4, ≥8, and ≥15 days per month during the period of heaviest lifetime drinking criteria were assessed in 530 American Indian participants. Exploratory factor analysis was used to examine the factor structure of the 10 AUD symptoms and each alcohol consumption criterion. Two‐parameter IRT models generated marginal maximum likelihood estimates for discrimination (a) and threshold (b) parameters for 10 DSM‐IV AUD symptoms and each consumption criterion. Differential item functioning (DIF) analysis was used to assess AUD symptom severity in groups defined by gender and age at interview. Results: The AUD symptoms of “Withdrawal” and “Activities Given Up” were the most severe symptoms. “Tolerance” and “Social/Interpersonal Problems” were the least severe. All AUD symptoms fell on the moderate portion of the severity continuum, except “Withdrawal,” which fell at the lower end of the severe portion. The consumption criterion of 5+/4+ (male/female) at ≥8 times per month demarcated the portion of the severity continuum where AUD symptoms began to occur at a probability of 50%. DIF analysis showed significant gender and age at interview differences for “Hazardous Use,”“Tolerance,” and “Activities Given Up,” but not for the other AUD symptoms. Conclusions: In this American Indian community sample, alcohol abuse and dependence did not represent distinct disorders. Only one AUD symptom was found outside the moderate portion of the underlying AUD severity continuum. Drinking 5+/4+ (male/female) drinks at a frequency of ≥8 times per month during the period of heaviest lifetime drinking was found to function well as both a risk and a diagnostic criterion for lifetime DSM‐IV AUD. DSM‐IV AUD symptom criteria, as currently assessed, may be limited in their ability to capture the full range of symptom severity of AUDs, at least in this high‐risk population.     

ADH1B polymorphism, alcohol consumption, and binge drinking in Slavic Caucasians: results from the Czech HAPIEE study

Background: Several genetic polymorphisms influence the risk of heavy alcohol consumption but it is not well understood whether the genetic effects are similar in different populations and drinking cultures, nor whether the genetic influences on binge drinking are similar to those seen for alcoholism. Methods: We have analyzed the effect of the Arg47His (rs1229984) variant within the alcohol dehydrogenase (ADH1B) gene on a range of drinking related variables in a large Eastern European Slavic population (Czech HAPIEE study), which recruited random samples of men and women aged 45–69 years in 7 Czech towns (3,016 males and 3,481 females with complete data). Drinking frequency, annual alcohol intake, prevalence of binge drinking (≥100 g in men and ≥60 g in women at least once a month) and the mean dose of alcohol per occasion were measured by the graduated frequency questionnaire. Alcohol intake in a typical week was used to define heavy drinking (≥350 g/wk in men and ≥210 g in women). Problem drinking (≥2 positive answers on CAGE) and negative consequences of drinking on different aspects of life were also measured. Results: The frequency of the His47 allele carriers was 11%. Homozygotes in the common allele (Arg47Arg), among both males and females, had significantly higher drinking frequency, and annual and weekly intake of alcohol than His47 carriers. The odds ratio of heavy drinking in Arg47Arg homozygotes versus His47 carriers was 2.1 (95% confidence intervals 1.1–3.2) in men and 2.2 (1.0–4.7) in women. In females, but not in males, Arg47Arg homozygotes had marginally significantly higher prevalence of binge drinking and mean alcohol dose per drinking session. There was no consistent association with problem drinking and negative consequences of drinking. Conclusions: The ADH1B genotype was associated with the frequency and volume of drinking but its associations with binge drinking and problem drinking were less consistent.     

Relation Between Executive Cognitive Functioning and the Adverse Consequences of Alcohol Use in Social Drinkers

The purpose of this study was to assess the relation between Executive Cognitive Functioning (ECF) and the adverse consequences of alcohol consumption. ECF encompasses "higher order" cognitive abilities involved in goal-directed behavior, such as attentional control, mental flexibility, planning, and self-monitoring. Impaired ECF has been shown to result in a variety of negative consequences, including excessive drug and alcohol use. Subjects were 79 nonalcoholic male social drinkers between 17 to 30 years of age. ECF was measured using three neuropsychological tests: the Wisconsin Card Sorting Test (WCST), the Conditional Associative Learning Test (CAT), and the Sequential Matching Memory Test (SMMT). Adverse drinking consequences were measured using the Drinker Inventory of Consequences (DrlnC). The DrlnC assesses drinking consequences in five domains: Physical, Intrapersonal, Interpersonal, Social Responsibility, and Impulse Control. Scores from the neuropsychological tests were reduced into two latent variables: one representing the WCST and the other representing the CAT and SMMT. The results indicated that errors on the CAT/SMMT variable were positively related to adverse consequences in each domain, except for physical consequences. A similar association was found between the WCST variable and impulse control consequences. These findings indicate that performance on tests measuring ECF is related to the severity of drinking consequences. Therefore, prevention and treatment outcomes may be improved by incorporating cognitive habilitation into current interventions.     

Patterns of alcohol consumption and alcohol-impaired driving in the United States

Background:  Alcohol-related motor vehicle crashes kill approximately 17,000 Americans annually and were associated with more than $51 billion in total costs in 2000. Relatively little is known about the drinking patterns of alcohol-impaired (AI) drivers in the United States.
Methods:  2006 Behavioral Risk Factor Surveillance System (BRFSS) was analyzed for alcohol consumption and self-reported AI driving among U.S. adults aged ≥18 years for all states. Alcohol consumption was divided into 4 categories: binge/heavy, binge/nonheavy, nonbinge/heavy, and nonbinge/nonheavy. Binge drinking was defined as ≥5 drinks for men or ≥4 drinks for women on one or more occasions in the past month, and heavy drinking was defined as average daily consumption of >2 drinks/day (men) or >1 drink/day (women). The prevalence of AI driving was examined by drinking pattern and by demographic characteristics. Logistic regression analysis was used to assess the association between drinking patterns and AI driving.
Results:  Five percent of drinkers were engaged in AI driving during the past 30 days. Overall, 84% of AI drivers were binge drinkers and 88% of AI driving episodes involved binge drinkers. By drinking category, binge/nonheavy drinkers accounted for the largest percentage of AI drivers (49.4%), while binge/heavy drinkers accounted for the most episodes of AI driving (51.3%). The adjusted odds of AI driving were 20.1 (95% CI: 16.7, 24.3) for binge/heavy, 8.2 (6.9, 9.7) for binge/nonheavy, and 3.9 (2.4, 6.3) for nonbinge/heavy drinkers, respectively.
Conclusions:  There is a strong association between binge drinking and AI driving. Most AI drivers and almost half of all AI driving episodes involve persons who are not heavy drinkers (based on average daily consumption). Implementing effective interventions to prevent binge drinking could substantially reduce AI driving.     

Exploring pregnancy-related changes in alcohol consumption between black and white women

Background: Although epidemiological data indicate that White women are more likely to drink and binge drink before pregnancy, fetal alcohol syndrome (FAS) is more common in the Black population than among Whites in the United States. Differences in drinking cessation between Black and White women who become pregnant may help explain the disparity in FAS rates. Methods: The study sample was comprised of 280,126 non‐Hispanic Black and White women, ages 18 to 44, from the Behavioral Risk Factor Surveillance System (BRFSS) 2001 to 2005 data sets. Predictors of reduction in alcohol consumption (in drinks per month) and binge drinking (>4 drinks on one occasion) by pregnant and non‐pregnant women were identified with logistic regression. The effect of interactions of pregnancy status with age, education, and Black or White race on drinks per month and binge occasions were explored using analysis of variance (ANOVA). Results: Pregnant White women averaged 79.5% fewer drinks per month than non‐pregnant White women (F = 1250.1, p < 0.001), and 85.4% fewer binge drinking occasions (F = 376, p < 0.001). Pregnant Black women averaged 58.2% fewer drinks per month than non‐pregnant Black women (F = 31.8, p < 0.001) and 64.0% fewer binge occasions (F = 13.8, p < 0.001). Compared to Black women, White women appear to make a 38% greater reduction in drinks per month, and a 33% greater reduction in binge occasions. Conclusions: Non‐Hispanic White women appear more likely to reduce drinks per month and binge drinking occasions than non‐Hispanic Black women during pregnancy. These findings may help explain disparities in FAS in the United States, though this cross‐sectional sample does not permit claims of causation. To better describe the impact of differential drinking reduction on FAS rates, future studies of longitudinal data should be done.     

Attention-deficit/hyperactivity disorder risk for heavy drinking and alcohol use disorder is age specific

BACKGROUND: This study was designed to assess age specificity in the risk for heavy drinking and alcohol use disorder (AUD) among adolescents and young adults with Attention-Deficit/Hyperactivity Disorder (ADHD) diagnosed in childhood. METHOD: Children diagnosed with ADHD (n=364 probands) were interviewed an average of 8 years later in the Pittsburgh ADHD Longitudinal Study, either as adolescents (11-17 years old) or as young adults (18-28 years of age). Demographically similar age-matched participants without ADHD were recruited as adolescents (n=120) or as adults (n=120) for comparison with the probands. Alcohol involvement was assessed comprehensively to include measures of heavy drinking that are standard in alcoholism research and prognostic of later alcohol-related problems. RESULTS: Results revealed age specificity in the association such that episodic heavy drinking (measured as 5+ drinks per occasion), drunkenness, DSM-IV AUD symptoms, and DSM-IV AUD were elevated among 15- to 17-year-old probands, but not among younger adolescents. Among young adults, drinking quantity and AUD were elevated among probands with antisocial personality disorder. Childhood predictors indexing antisocial behavior were also examined. CONCLUSIONS: The age- specificity of these findings helps to explain prior inconsistencies across previous studies regarding risk for alcohol-related outcomes among children with ADHD.     

Adolescent C57BL/6J mice show elevated alcohol intake, but reduced taste aversion, as compared to adult mice: a potential behavioral mechanism for binge drinking

Background: Binge alcohol drinking during adolescence is a serious health problem that may increase future risk of an alcohol use disorder. Although there are several different procedures by which to preclinically model binge‐like alcohol intake, limited‐access procedures offer the advantage of achieving high voluntary alcohol intake and pharmacologically relevant blood alcohol concentrations (BACs). Therefore, in the current study, developmental differences in binge‐like alcohol drinking using a limited‐access cycling procedure were examined. In addition, as alcohol drinking has been negatively correlated with sensitivity to the aversive properties of alcohol, we examined developmental differences in sensitivity to an alcohol‐induced conditioned taste aversion (CTA). Methods: Binge‐like alcohol consumption was investigated in adolescent (4 weeks) and adult (10 weeks) male C57BL/6J mice for 2 to 4 h/d for 16 days. Developmental differences in sensitivity to an alcohol‐induced CTA were examined in adolescent and adult mice, with saline or alcohol (3 or 4 g/kg) repeatedly paired with the intake of a novel tastant (NaCl). Results: Adolescent mice showed a significant increase in alcohol intake as compared to adults, with adolescents achieving higher BACs and increasing alcohol consumption over successive cycles of the binge procedure. Conversely, adolescent mice exhibited a dose‐dependent reduction in sensitivity to the aversive properties of alcohol, as compared to adult mice, with adolescent mice failing to develop a CTA to 3 g/kg alcohol. Finally, extinction of an alcohol CTA was observed following conditioning with a higher dose of alcohol in adolescent, versus adult, mice. Conclusions: These results indicate that adolescent mice consume more alcohol, per kilogram body weight, than adults in a binge‐like model of alcohol drinking and demonstrate a blunted sensitivity to the conditioned aversive effects of alcohol. Overall, this supports a behavioral framework by which heightened binge alcohol intake during adolescence occurs, in part, via a reduced sensitivity to the aversive properties of alcohol.     

Prevalence of alcohol dependence among excessive drinkers in New Mexico

BACKGROUND: Excessive alcohol consumption claims more than 75,000 lives in the United States each year. The prevalence of alcohol dependence among excessive drinkers is not well known. METHODS: Data from the 2002 Behavioral Risk Factor Surveillance System (BRFSS) in New Mexico were used to assess the prevalence of excessive drinking, including binge drinking, heavy drinking, alcohol-impaired driving, and alcohol dependence. RESULTS: Of 4,761 respondents, 16.5% were excessive drinkers; 14.4% binge drank and 1.8% were alcohol dependent. While the rates of alcohol dependence were higher among the youngest age group, males, those with some college education, and those of race/ethnicity other than White, non-Hispanic, only differences by age were statistically significant. The prevalence of alcohol dependence was the highest among those who reported alcohol-impaired driving in the past 30 days (15.9%), and was lower among those who reported heavy drinking (13.4%) and binge drinking (8.1%). CONCLUSIONS: Although 16.5% of New Mexico adults had at least 1 type of excessive drinking, only 1.8% of all adults met the criteria for alcohol dependence. Furthermore, only a minority of those who reported binge drinking, heavy drinking, or alcohol-impaired driving met the criteria for alcohol dependence. This suggests that most alcohol problems in New Mexico are likely due to excessive drinking among persons who are not alcohol dependent. The adverse health and social consequences associated with excessive drinking are not limited to those who are alcohol dependent, but extend to a broader range of problem drinkers across the population.     

Deficits in eye movement control in children with fetal alcohol spectrum disorders

BACKGROUND: Prenatal exposure to alcohol can result in a spectrum of adverse developmental outcomes in offspring, collectively termed fetal alcohol spectrum disorders (FASD). Deficits in executive function--the psychological processes involved in controlling voluntary goal-oriented behavior--are prevalent in FASD. Oculomotor tasks have been designed as highly sensitive tools to evaluate components of executive function. Because of the extensive overlap in the brain areas controlling eye movements and those affected in FASD, we hypothesized that individuals with FASD display specific neurobehavioral abnormalities that can be quantified with eye movement testing. METHODS: Subjects (8-12 years old) were instructed to look either toward (prosaccade) or away from (antisaccade) a stimulus that appeared in the peripheral visual field. Two fixation conditions were used. In the gap condition, the central fixation point (FP) was removed before the appearance of the peripheral stimulus; in the overlap condition, the FP remained illuminated. Saccadic reaction times (SRTs, time from stimulus appearance to saccade initiation), direction errors (saccades made in the incorrect direction relative to instruction), and express saccades (short-latency: SRT=90-140 ms) were measured to assess automatic and volitional saccade control. RESULTS: Compared with controls, FASD children had elongated reaction times, excessive direction errors, and no express saccades. Metric analysis of correct prosaccades revealed a trend toward increased saccadic duration and decreased saccadic velocity in FASD subjects. CONCLUSION: These results reflect deficits in executive function and motor control, and are consistent with dysfunction of the frontal lobes, possibly due to disrupted inhibitory mechanisms. Therefore, eye movement tasks may be powerful and easy tools for assessing executive function deficits in FASD.