Alcoholism, clinical and experimental research最新文献

Background: Researchers have long sought to understand how individuals respond to alcohol in social settings with the aim of elucidating pathways of risk for alcohol use disorder (AUD). But studies that incorporate a social context are still outnumbered by those that examine alcohol's subjective effects among participants drinking alcohol in isolation. Further, perhaps due to the challenges of capturing automatic affective processes in these settings, prior studies of alcohol response in social context have relied mainly on self-report measures, and so relatively little is known about alcohol's psychophysiological effects in social settings.

Methods: Using a novel paradigm that integrated alcohol-administration procedures, startle methodology, and social context, this study examined the impact of alcohol and social context on startle eyeblink reflex among 40 social drinkers.

Results: Results indicated that there was a significant effect of group presence, indicating that startle magnitude was larger when people were alone than with others. There was a significant group presence-by-alcoholic beverage interaction, with the effect of alcohol being significantly larger when people were alone versus with others. These effects were found both for the startle habituation data and during the picture-viewing task.

Conclusions: Results of this study highlight the importance of considering the presence of other individuals for understanding alcohol response and mechanisms of AUD risk. Findings are discussed in light of both emotional and cognitive correlates of startle reflex magnitude. Future research should examine these effects within larger samples of participants and further explore mechanisms that might underlie these effects.

Background: The directionality of the relationship between impulsivity and heavy drinking patterns remains unclear. Recent research suggests it could be reciprocal and depends on different facets of impulsivity and different patterns of drinking. The aim of this study was to analyze this potential reciprocal relationship between self-reported and behavioral measures of impulsivity and sensation seeking with specific patterns of heavy drinking in a sample of Spanish adolescents across 2 years.

Methods: The study has a cross-lagged prospective design in which participants were evaluated 3 times over 2 years (once a year). Participants were 1,430 adolescents (53.9% male; mean age at study commencement = 13.02, SD = 0.51) from 22 secondary schools in Spain. Computerized versions of the following instruments were used: 2 subscales of Impulsive Sensation Seeking, 2 behavioral measures (Stroop Test and Delay Discounting [DD] task), frequency of intoxication episodes (IE), and the Rutgers Alcohol Problem Index to evaluate alcohol-related problems (ARP). Random intercepts cross-lagged panel models of reciprocal relationships between impulsivity measures and alcohol use outcomes were used.

Results: Individual levels of self-reported impulsivity and sensation seeking significantly predicted prospective involvement in IE and ARP. Performance in behavioral measures (Stroop Test and DD) did not predict subsequent heavy drinking or alcohol problems. No measure of drinking was found to be a significant predictor of prospective changes in impulsivity.

Conclusions: Within-person levels of self-reported impulsivity and sensation seeking significantly predicted further heavy drinking from as early as 13 years old, whereas behavioral measures were not predictive. In our study, neither IE nor ARP predicted prospective changes in impulsivity. Further studies should address additional specific relationships between facets of impulsivity and specific outcomes of heavy drinking.

Background: Modifying attentional processes with attentional bias modification (ABM) might be a relevant add-on to treatment in addiction. This study investigated whether influencing cortical plasticity with transcranial direct current stimulation (tDCS) could increase training effects. tDCS could also help alcohol-dependent patients to overcome craving and reduce relapse, independent of training. These approaches were combined to investigate effects in the treatment of alcoholism.

Methods: Ninety-eight patients (analytical sample = 83) were randomly assigned to 4 groups in a 2-by-2 factorial design. Patients received 4 sessions of ABM (control or real training) combined with 2 mA tDCS (active: 20 minutes or sham: 30 seconds) over the left dorsolateral prefrontal cortex. Alcohol bias and craving were assessed, and treatment outcome was measured as relapse after 1 year.

Results: Attentional bias scores indicated that during the training only the group with active tDCS and real ABM displayed an overall avoidance bias (p < 0.05). From pre- to postassessment, there were no main or interaction effects of tDCS and ABM on the bias scores, craving, or relapse (p > 0.2). However, effects on relapse after active tDCS were in the expected direction.

Conclusions: There was no evidence of a beneficial effect of tDCS or ABM or the combination. Whether the absence of effect was due to issues with the outcome measurements (e.g., lack of craving, high dropout, and unreliable measurements) or aspects of the intervention should be further investigated.

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.