Alcoholism, clinical and experimental research最新文献

Background: Choline, an essential nutrient, serves as a methyl-group donor for DNA methylation and is a constituent of the neurotransmitter acetylcholine and a precursor to major components of cell membranes. Findings from animal studies suggest that choline supplementation during pregnancy can mitigate adverse effects of prenatal alcohol exposure on growth and neurocognitive function. We conducted a randomized, double-blind exploratory trial to examine feasibility and acceptability of a choline supplementation intervention during pregnancy.

Methods: Seventy heavy drinkers, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of 2 g of choline or a 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. Adherence was assessed by collecting used and unused drink packets on a monthly basis and tabulating the number used. Side effects were assessed in monthly interviews. Blood samples obtained at enrollment and at 4 and 12 weeks after randomization were assayed for plasma choline concentration.

Results: Adherence was good-to-excellent (median doses taken = 74.0%; interquartile range = 53.9 to 88.7%) and was not related to a range of sociodemographic characteristics or to alcohol consumption ascertained using a timeline follow-back interview. By 4 weeks, plasma choline concentrations were significantly higher in the choline supplementation than the placebo arm, and this group difference continued to be evident at 12 weeks. The only side effect was a small increase in nausea/dyspepsia. No effects were seen for diarrhea, vomiting, muscle stiffness, blood pressure, or body odor changes.

Conclusions: This study demonstrated that a choline supplementation program with very heavy drinkers during pregnancy is feasible even among highly disadvantaged, poorly educated women. The broad acceptability of this intervention is indicated by our finding that adherence was not related to maternal education, intellectual function, depression, nutritional status, or alcohol use.

Background: Alcohol is often consumed with opioids and alcohol misuse interferes with treatment for opioid use disorder (OUD). Drug misuse is associated with worse alcohol use disorder (AUD) treatment outcomes, yet no studies have investigated the role of opioid misuse in AUD treatment outcomes.

Methods: We conducted secondary analyses of the medication conditions of the COMBINE study (n = 1,226), a randomized clinical trial of medications (acamprosate and/or naltrexone) and behavioral interventions (medication management and/or behavioral intervention) for alcohol dependence. We examined associations between baseline opioid misuse and the use of cannabis and other drugs with time to first drinking day, time to first heavy drinking day, and the frequency and intensity of drinking during treatment and 1 year following treatment, based on latent profile analysis. Opioid misuse was defined as use of illicit or prescription opioids without a prescription or not as directed in the previous 6 months, in the absence of OUD. Self-reported cannabis and other drug use were also examined. Seventy individuals (5.7%) met the opioid misuse definition and 542 (44.2%) reported use of cannabis or other drugs without opioid misuse. We also examined medication adherence as a potential mediator.

Results: Baseline opioid misuse significantly predicted the time to first heavy drinking day (OR = 1.38 [95% CI: 1.13, 1.64], p = 0.001) and a higher probability of being in a heavier and more frequent drinking profile at the end of treatment (OR = 2.90 [95% CI: 1.43, 5.90], p = 0.003), and at 1 year following treatment (OR = 2.66 [95% CI: 1.26, 5.59], p = 0.01). Cannabis and other drug use also predicted outcomes. Medication adherence partially mediated the association between opioid misuse, cannabis use, other drug use, and treatment outcomes.

Conclusions: Opioid misuse and other drug use were associated with poorer AUD treatment outcomes, which was partially mediated by medication adherence. Clinicians and researchers should assess opioid misuse and other drug use in patients undergoing AUD treatment.

Background: Alcohol intoxication facilitates interpersonal aggression, but this effect depends on person and situation characteristics. Using the Alcohol Myopia Model, we examined the joint influence of alcohol, trait anger, and state anger on the association between perceived quarrelsomeness in an interaction partner and quarrelsome behavior in naturally occurring interpersonal interactions.

Methods: Using an event-contingent recording method over a 20-day period, community adults reported their perception of an interaction partner's quarrelsome behavior, their own anger and quarrelsome behavior, and the number of alcohol drinks consumed up to 3 hours prior to an interpersonal interaction.

Results: Results revealed that alcohol consumption and trait anger jointly moderated the association between perceived quarrelsomeness and quarrelsome behavior indirectly via state anger. Heightened anger experience accounted for increased quarrelsome behavior in response to perceived quarrelsomeness among higher trait anger individuals who reported increased alcohol consumption. When no alcohol was consumed, no such difference in quarrelsome behavioral response was found between low and high trait anger individuals.

Conclusions: Findings suggest that alcohol consumption may strengthen the influence of perceived quarrelsomeness on a person's own quarrelsome behavior among individuals with a readiness to experience anger. Intense anger experience may undermine these individuals' ability to inhibit aggressive behaviors when under the influence of alcohol.

Background: While there is a substantial literature on the efficacy of brief motivational intervention (BMI) for college student drinkers, research has focused less on young adults who do not attend a 4-year college, despite their elevated risk for excessive alcohol use and associated harmful consequences.

Methods: This randomized controlled trial (NCT01546025) compared the efficacy of BMI to a time-matched attention control intervention (relaxation training [REL]) for reducing alcohol consumption and related negative consequences in an underage young adult sample. BMI was tailored to the developmental transition out of high school for young adults who were not immediately planning to enroll in a 4-year college. Non-treatment-seeking underage drinkers who reported past-month heavy drinking (N = 167; ages 17 to 20; 42% female; 59% non-Hispanic White) were randomly assigned to receive a single session of BMI or REL. Outcomes were evaluated 6 weeks and 3 months postintervention via in-person assessments.

Results: Generalized estimating equation models provided strong support for the efficacy of BMI for reducing harmful drinking in these young adults. Compared to REL, and after controlling for baseline covariates including gender, those who received BMI subsequently reported significantly fewer average drinks per week, percent drinking days, percent heavy drinking days, lower peak and typical estimated blood alcohol concentration on drinking days, and fewer adverse consequences of drinking (all ps < 0.05). These between-group effects did not weaken over the course of the 3-month follow-up period.

Conclusions: These findings demonstrate an efficacious approach to tailoring BMI for non-college-attending young adults. Future research should replicate and extend these findings over a longer follow-up period.

Background: Heavy drinking among college students is a significant public health concern that can lead to profound social and health consequences, including alcohol use disorder. Behavioral economics posits that low future orientation and high valuation of alcohol (alcohol demand) combined with deficits in alternative reinforcement increase the likelihood of alcohol misuse. Despite this, no study has examined the incremental utility of all 3 variables simultaneously in a comprehensive model.

Methods: This study uses structural equation modeling to test the associations between behavioral economic variables-alcohol demand (latent), future orientation (measured with a delay discounting task and the Consideration of Future Consequences [CFC] scale), and proportionate substance-related reinforcement-and alcohol consumption and problems among 393 heavy drinking college students. Two models are tested as follows: (i) an iteration of the reinforcer pathology model that includes an interaction between future orientation and alcohol demand; and (ii) an alternative model evaluating the interconnectedness of behavioral economic variables in predicting problematic alcohol use.

Results: The interaction effects in Model 1 were nonsignificant. Model 2 suggests that greater alcohol demand and proportionate substance-related reinforcement are associated with greater alcohol consumption and problems. Furthermore, CFC was associated with alcohol-related problems and lower proportionate substance-related reinforcement but was not significantly associated with alcohol consumption or alcohol demand. Finally, greater proportionate substance-related reinforcement was associated with greater alcohol demand.

Conclusions: Our results support the validity of the behavioral economic reinforcer pathology model as applied to young adult heavy drinking.

Background: Alcohol use disorders are characterized by a complex behavioral symptomatology, which includes the loss of control over alcohol consumption and the emergence of a negative affective state when alcohol is not consumed. Some of these symptoms can be recapitulated in rodent models, for instance following chronic intermittent ethanol (EtOH; CIE) vapor inhalation. However, the detection of negative affect in mice withdrawn from CIE has proven challenging and variable between strains. This study aimed to detect reliable indices of negative emotionality in CIE-exposed C57BL/6J (C57) and DBA/2J (DBA) mice. Males were used because they are known to escalate their voluntary EtOH consumption upon CIE exposure, which is hypothesized to be driven by negative reinforcement (relief from negative affect).

Methods: Adult male mice were exposed to 4 to 6 weeks of CIE and were evaluated 3 to 10 days into withdrawal in the social approach, novelty-suppressed feeding, digging, marble burying, and bottle brush tests.

Results: Withdrawal from CIE decreased sociability in DBA mice but not in C57 mice. Conversely, hyponeophagia was exacerbated by CIE in C57 mice but not in DBA mice. Withdrawal from CIE robustly increased digging activity in both strains, even in the absence of marbles. Aggressive responses to bottle brush attacks were elevated in both C57 and DBA mice following CIE exposure, but CIE had an opposite effect on defensive responses in the 2 strains (increase in C57 vs. decrease in DBA).

Conclusions: Our results indicate that withdrawal from CIE elicits negative emotionality in both C57 and DBA mice, but different tests need to be used to measure the anxiogenic-like effects of withdrawal in each strain. Increased digging activity and irritability-like behavior represent novel indices of affective dysfunction associated with withdrawal from CIE in both mouse strains. Our findings enrich the characterization of the affective symptomatology of protracted withdrawal from CIE in mice.