Alcoholism, clinical and experimental research最新文献

Background: Alcohol use and its associated problems are on the rise in China. In this study, we examined the associations between alcohol use and cognitive functioning in a representative sample of adults aged 45 years and older in China.

Methods: Baseline data for 16,328 participants of the China Health and Retirement Longitudinal Study were analyzed. Alcohol use was measured by drinking status (never, former, moderate, and at-risk drinkers), number of standard drinks per week, and years of drinking. Cognitive functioning was assessed for visuospatial ability, episodic memory, orientation/attention, and overall cognitive functioning. Multivariate linear and logistic regressions were used to examine the independent association between alcohol use and cognitive functioning controlling for age, gender, education, domestic partner status, and depressive symptoms.

Results: The study participants were, on average, 66 years old (median 59, range 45 to 102). The prevalence of ever drinking during lifetime and current at-risk drinking (>14 drinks per week) in this population was 34.6 and 6.7%, respectively. Drinking was more common among men with 48.8% being ever drinkers and 14.4% current at-risk drinkers, respectively. At-risk drinkers, compared to people who never drank alcohol, had worse episodic memory (β = -0.11, p = 0.048). Moreover, number of standard drinks per week was associated with worse episodic memory (β = -0.001, p = 0.02). None of the other measures of alcohol use was associated with the overall or domain-specific cognitive functioning.

Conclusions: At-risk drinking status was associated with worse episodic memory. Clinicians should incorporate alcohol use assessment into routine care for middle-aged and older adults in China and provide them with resources and strategies to effectively manage their alcohol use. This may help preserve episodic memory in this population.

Background: Blackouts-or memory loss for all or part of a drinking event-are reliable predictors of alcohol-related consequences. Studies suggest a distinction between en bloc (complete memory loss) and fragmentary (off-and-on memory loss) blackouts; however, research has not consistently differentiated between these 2 forms of blackout. This study aimed to validate the distinction between en bloc and fragmentary blackouts among young adults.

Methods: Data were collected using qualitative (Study 1) and quantitative (Study 2) research methods. Participants in both studies were college students with a history of alcohol-induced memory impairment. They were recruited using community advertisement (Study 1, N = 50, 56% female) and Qualtrics survey panels (Study 2, N = 350, 56% female). Study 1 participants engaged in 8 focus groups. Discussions were audio-recorded, transcribed verbatim, and coded using applied thematic analysis. Findings guided assessment of en bloc and fragmentary blackout in Study 2. In Study 2, a separate sample of participants completed an online survey assessing drinking behavior, alcohol-induced memory impairment, and theoretical correlates of en bloc and fragmentary blackouts.

Results: Study 1 participants differentiated between en bloc and fragmentary blackouts (which they referred to as "blackouts" and "brownouts," respectively) based on duration and extent of memory loss. They indicated that blackouts occur along a continuum, with en bloc "blackouts" at the extreme. They also stated that the term "blackout drinking" does not always imply memory loss. Study 2 participants reported higher rates of "brownouts" (81%) than "blackouts" (54%). They reported less negative outcome expectancies and attitudes, greater personal approval, higher prevalence estimates, lower self-efficacy, and stronger intentions for "brownouts" than "blackouts" (p < 0.001). Women perceived "blackouts/brownouts" as more prevalent than men and reported lower intentions to experience "blackouts" (p < 0.005).

Conclusions: Young adults are more permissive of fragmentary than en bloc blackout. En bloc blackouts may be a target for future interventions.

Background: Life expectancy is greatly reduced in individuals presenting alcohol use disorders and chronic smoking. Literature studies suggest that common mechanisms may apply to the chronic use and relapse of both alcohol and nicotine. It is hypothesized that an increased brain oxidative stress and neuroinflammation are involved in perpetuating these conditions and that a common treatment may be considered for both.

Methods: Rats bred as high ethanol (EtOH) drinkers (UChB) were allowed chronic access to EtOH solutions and water and were thereafter deprived of EtOH for a prolonged period, subsequently allowing reaccess to EtOH, which leads to marked relapse binge-like drinking. Separately, EtOH-naïve animals were chronically administered nicotine intraperitoneally and tested under either a conditioned place preference (CPP) reinstatement condition or allowed a free-choice drinking of nicotine solutions and water. Oral N-acetylcysteine (NAC) (100 mg/kg) was administered daily to the animals to determine its effect on both chronic voluntary EtOH and nicotine intake, on EtOH relapse and nicotine-CPP reinstatement. Oxidative stress was evaluated in hippocampus as the oxidized/reduced glutathione ratio (GSSG/GSH), and neuroinflammation by glial fibrillary acidic protein (GFAP) immunohistochemistry.

Results: Marked increases in hippocampal oxidative stress (GSSG/GSH) and neuroinflammation (astrocyte reactivity, GFAP) were observed after both chronic EtOH and chronic nicotine treatment. Oral NAC administration (i) fully abolished the increased oxidative stress and the neuroinflammation induced by both drugs, (ii) greatly inhibited EtOH intake (70%) and EtOH relapse binge-like drinking (76%), and (iii) markedly inhibited (90%) voluntary nicotine intake and fully suppressed nicotine-CPP reinstatement.

Conclusions: Data indicate that (i) oxidative stress and neuroinflammation are tightly associated with chronic EtOH and nicotine intake and drug relapse and (ii) NAC inhibits the relapse for both drugs, suggesting that the oral chronic administration of NAC may be of value in the concomitant treatment of alcohol and nicotine use disorders.

Background: Attitudes toward driving after drinking are strongly predictive of drinking and driving behavior. This study tested working memory capacity (WMC) as a moderator of the association between attitudes and drinking and driving behavior. Consistent with dual process models of cognition, we hypothesized that the association between perceived danger and drinking and driving would be stronger for individuals with higher WMC.

Methods: Participants (N = 161) enrolled in larger alcohol administration study were randomly assigned to an alcohol (n = 57), placebol (n = 52), or control (n = 52, not included) beverage condition. Past-year frequency of driving after drinking and WMC were assessed at baseline. Attitudes were assessed by asking participants to rate the perceived danger of driving at their current level of intoxication twice on the ascending limb (AL1, AL2), at peak breath alcohol concentration (BrAC), and twice on the descending limb (DL1, DL2).

Results: Analyses across the BrAC curve indicated that the hypothesized interaction was observed for the alcohol but not placebo condition. Analyses for each assessment point indicated that the interaction was significant for the ascending limb and peak BrAC. In the alcohol condition, for those higher in WMC, lower perceived dangerousness was strongly associated with increased driving after drinking (AL1: incident rate ratios [IRR] = 5.87, Wald's χ²  = 12.39, p = 0.006, 95% CI [2.19, 15.75]; AL2: IRR = 8.17, Wald's χ²  = 11.39, p = 0.001, 95% CI [2.41, 27.66]; Peak: IRR = 5.11, Wald's χ²  = 9.84, p = 0.002, 95% CI [1.84, 14.16]). Associations were not significant at low WMC.

Conclusions: Results suggest that individuals higher in WMC are more likely to act consistently with their explicit attitudes toward drinking and driving. Findings may have implications for existing drinking and driving interventions and suggest the potential for novel interventions targeting implicit associations or WMC.

Background: Demonstrating clinically meaningful benefits of alcohol use disorder treatments is challenging.

Methods: We report findings from a 12-week, phase 2, randomized, double-blind, placebo-controlled study of samidorphan (1, 2.5, or 10 mg/d) in adults with alcohol use disorder (NCT00981617). The primary end point was percentage of subjects with no heavy drinking days (PSNHDD) during weeks 5 to 12; secondary end points included alcohol consumption measures, craving, and patient-rated outcomes.

Results: Altogether, 406 patients were included in the full analysis set (101, 104, 100, and 101 in the placebo, samidorphan 1, 2.5, and 10 mg treatment groups, respectively). There was no statistical difference between samidorphan and placebo groups on PSNHDD during weeks 5 to 12. However, dose-dependent reductions in cumulative rate of heavy drinking days were observed (-41%, p < 0.001 for samidorphan 10 mg/d vs. placebo; -30 and -32% for samidorphan 2.5 and 1 mg, p < 0.05 for both). A higher percentage of samidorphan- than placebo-treated patients had a ≥2-category downshift in World Health Organization (WHO) risk levels of drinking. There were significant reductions from baseline with samidorphan versus placebo in alcohol craving (for samidorphan 10 mg: -38.2 [standard error: 2.9] vs. placebo: -30.2 [2.8]; p = 0.044). On a Patient Global Assessment of Response to Therapy (PGART), samidorphan 10 mg was superior to placebo at 4, 8, and 12 weeks (p < 0.001, p < 0.001, p < 0.01, respectively). Improvement in PGART correlated with a reduction in craving and a decrease in WHO risk level.

Conclusions: Results for the primary outcome measure PSNHDD were negative, but at variance with other measures and patient treatment perceptions that may be relevant for interventional studies. These findings highlight the importance of understanding the most relevant outcomes to patients and incorporating and prioritizing patient-centered outcomes when assessing interventions for alcohol use disorder.

Background: Child maltreatment (CM) is robustly associated with youth risk for addictive behaviors, and recent findings suggest that this may be mediated through impulsive discounting of future rewards. However, research indicates that youth self-regulation (emotional and cognitive), particularly in peer contexts, is critical to consider in the study of decision making. This study aimed to examine the indirect link between CM and alcohol and other drug use problems, through delayed reward discounting (DRD), among a community sample of emerging adults. Further, this investigation aimed to examine whether this indirect link was moderated by heart rate variability (HRV), a physiological proxy for regulation of stress reactivity.

Methods: A sample of emerging adults (N = 225; M_age  = 21.56; SD_age  = 2.24; 52.9% female) was assessed at 2 time points, with 1 year between assessments. The sample was comprised of rural emerging adults from lower socioeconomic backgrounds. DRD was examined using a monetary choice task, and HRV reactivity was derived during a social stress task.

Results: Increased CM experiences were significantly linked to riskier DRD. HRV reactivity amplified the indirect effect between CM and alcohol use problems via riskier DRD.

Conclusions: The results demonstrate that the connection between CM and alcohol use problems via impulsive decision making is modulated by acute stress response reactivity, as indexed by HRV.

Background: Conditioned taste aversion (CTA) learning is a highly specialized form of conditioning found across taxa that leads to avoidance of an initially neutral stimulus, such as taste or odor, that is associated with, but is not the cause of, a detrimental health condition. This study examines if honey bees (Apis mellifera L.) develop ethanol (EtOH)-induced CTA.

Methods: Restrained bees were first administered a sucrose solution that was cinnamon scented, lavender scented, or unscented, and contained either 0, 2.5, 5, 10, or 20% EtOH. Then, 30 minutes later, we used a proboscis extension response (PER) conditioning procedure where the bees were taught to associate either cinnamon odor, lavender odor, or an air-puff with repeated sucrose feedings. For some bees, the odor of the previously consumed EtOH solution was the same as the odor associated with sucrose in the conditioning procedure. If bees are able to learn EtOH-induced CTA, they should show an immediate low level of response to odors previously associated with EtOH.

Results: We found that bees did not develop CTA despite the substantial inhibitory and aversive effects EtOH has on behavior. Instead, bees receiving a conditioning odor that was previously associated with EtOH showed an immediate high level of response. While this demonstrates bees are capable of one-trial learning common to CTA experiments, this high level of response is the opposite of what would occur if the bees developed a CTA. Responding on subsequent trials also showed a general inhibitory effect of EtOH. Finally, we found that consumption of cinnamon extract reduced the effects of EtOH.

Conclusions: The honey bees' lack of learned avoidance to EtOH mirrors that seen in human alcoholism. These findings demonstrate the usefulness of honey bees as an insect model for EtOH consumption.

Background: Supersized alcopops are a class of single-serving beverages popular among underage drinkers. These products contain large quantities of alcohol. This study examines the extent to which young adults recognize how intoxicated they would become from consuming these products.

Methods: The study sample included 309 undergraduates who had consumed alcohol within the past year. Thirty-two sections of a college English course were randomized to 1 of 2 survey conditions, based on hypothetical consumption of supersized alcopops or beer of comparable liquid volume. Students were provided an empty can of 1 of the 2 beverages to help them answer the survey questions. Equation-calculated blood alcohol concentrations (BACs)-based on body weight and sex-were compared to the students' self-estimated BACs for consuming 1, 2, and 3 cans of the beverage provided to them.

Results: In adjusted regression models, students randomized to the supersized alcopop group greatly underestimated their BAC, whereas students randomized to the beer group overestimated it. The supersized alcopop group underestimated their BAC by 0.04 (95% confidence interval [CI]: 0.034, 0.053), 0.09 (95% CI: 0.067, 0.107), and 0.13 g/dl (95% CI: 0.097, 0.163) compared to the beer group. When asked how much alcohol they could consume before it would be unsafe to drive, students in the supersized alcopop group had 7 times the odds of estimating consumption that would generate a calculated BAC of at least 0.08 g/dl, compared to those making estimates based on beer consumption (95% CI: 3.734, 13.025).

Conclusions: Students underestimated the intoxication they would experience from consuming supersized alcopops. Revised product warning labels are urgently needed to clearly identify the number of standard drinks contained in a supersized alcopop can. Moreover, regulations are needed to limit alcohol content of single-serving products.

Background: We recently demonstrated the acceptability and feasibility of a randomized, double-blind choline supplementation intervention for heavy drinking women during pregnancy. In this study, we report our results relating to the efficacy of this intervention in mitigating adverse effects of prenatal alcohol exposure (PAE) on infant growth and cognitive function.

Methods: Sixty-nine Cape Coloured (mixed ancestry) heavy drinkers in Cape Town, South Africa, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of either 2 g of choline or placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. The primary outcome, eyeblink conditioning (EBC), was assessed at 6.5 months. Somatic growth was measured at birth, 6.5, and 12 months, recognition memory and processing speed on the Fagan Test of Infant Intelligence, at 6.5 and 12 months.

Results: Infants born to choline-treated mothers were more likely to meet criterion for conditioning on EBC than the placebo group. Moreover, within the choline arm, degree of maternal adherence to the supplementation protocol strongly predicted EBC performance. Both groups were small at birth, but choline-treated infants showed considerable catch-up growth in weight and head circumference at 6.5 and 12 months. At 12 months, the infants in the choline treatment arm had higher novelty preference scores, indicating better visual recognition memory.

Conclusions: This exploratory study is the first to provide evidence that a high dose of choline administered early in pregnancy can mitigate adverse effects of heavy PAE on EBC, postnatal growth, and cognition in human infants. These findings are consistent with studies of alcohol-exposed animals that have demonstrated beneficial effects of choline supplementation on classical conditioning, learning, and memory.

Background: We examined how mothers' protective parenting and alcohol use influenced changes in offspring's heavy drinking among a sample of African American youth. The conceptual model also tested indirect effects of mothers' behaviors, through changes in the youths' social images (i.e., prototypes) of heavy drinkers, derived from the prototype willingness (PW) model.

Methods: Participants were 686 emerging adults (55% female) from the Family and Community Health Study (FACHS), an ongoing prospective study of African American families. Three waves of FACHS data were used as follows: T3 during 10th grade (M age = 16.3 years), T4 shortly after high school (M age = 19.4 years), and T5 3 years later (M age = 22.1 years). Mothers' self-reports of protective parenting and alcohol use were assessed at T4. Two separate path models tested the study hypotheses. The first model specified direct and indirect effects of mothers' protective parenting and alcohol use. The second model added interaction terms between the protective parenting behaviors and mothers' alcohol use. The analyses were first conducted using the full sample and then repeated separately for female and male participants.

Results: Maternal alcohol use had a positive and direct effect on offspring's alcohol use. Mothers' endorsement of alcohol-related rules inhibited normative increases in the favorability of the offspring's social image of heavy drinkers (prototype) while her warmth was positively related to these increases. Maternal alcohol use amplified the positive association between mothers' warmth and the daughters' increased drinking. For sons, maternal alcohol use increased the positive association between alcohol-related rules and increased prototype favorability.

Conclusions: Results indicated clear gender differences in how mothers' behaviors influence her offspring's alcohol use during the transition to emerging adulthood. Interventions that target culturally specific risk and protective factors within the family environment are needed to reduce health disparities among this vulnerable population of youth.