Alcoholism, clinical and experimental research最新文献

Background: Proton magnetic resonance spectroscopy (¹ H-MRS) studies have demonstrated abnormal levels of a variety of neurometabolites in inpatients/outpatients with alcohol use disorder (AUD) following acute alcohol withdrawal relative to healthy controls. In contrast, few studies have compared neurometabolite levels between less severe, treatment-naïve AUD individuals and light drinkers (LD) or related them to recent alcohol consumption. The present study compared neurometabolite levels between treatment-naïve AUD and LD individuals.

Methods: Twenty treatment-naïve individuals with AUD and 20 demographically matched LD completed an ¹ H-MRS scan, approximately 2.5 days following their last reported drink. ¹ H-MRS data were acquired in dorsal anterior cingulate (dACC) using a 2-dimensional J-resolved point-resolved spectroscopy sequence. dACC neurometabolite levels, with a focus on glutamate, glutamine, and GABA, were compared between AUD and LD participants. The associations between metabolite levels and recent drinking were explored.

Results: AUD participants had significantly lower concentrations of GABA (Cohen's d = 0.79, p = 0.017) and glutamine (Cohen's d = 1.12, p = 0.005), but not glutamate (Cohen's d = 0.05, p = 0.893), relative to LD. As previously reported, AUD participants' glutamate and N-acetylaspartate concentrations were inversely associated with their number of heavy drinking days. In contrast, neither number of drinking (mean p = 0.56) nor heavy drinking (mean p = 0.47) days were associated with metabolite concentrations in LD.

Conclusions: The present study demonstrated significantly lower levels of prefrontal γ-aminobutyric acid and glutamine in treatment-naïve individuals with AUD relative to LD. Whether these findings reflect the neurotoxic consequence and/or neuroadaptive response of alcohol consumption versus a predrinking trait, and therefore a more durable neurochemical disturbance, awaits elucidation from longitudinal studies.

Background: Alcoholic gastritis, a superficial erosive disease of the stomach, is a common manifestation of risky alcohol use. In contrast, cannabis which is frequently co-used with alcohol suppresses gastric acidity and might counteract the deleterious effect of alcohol on the gastric mucosa. However, no clinical study has examined the impact of cannabis use on the development of alcoholic gastritis among risky alcohol users.

Methods: We analyzed hospital discharge records of adults (age ≥ 18 years), from 2014 of the Nationwide Inpatient Sample, with a diagnosis of risky alcohol use (n = 316,916). We used a propensity-based matching algorithm to match cannabis users to nonusers on 1:1 ratio (30,713: 30,713). We then measured the adjusted relative risk (aRR) for having alcoholic gastritis using conditional Poisson regression models with generalized estimating equations.

Results: Our study revealed that among risky alcohol users, cannabis co-users have a lower prevalence of alcoholic gastritis compared to noncannabis users (1,289 [1,169 to 1,421] vs. 1,723 [1,583 to 1,875] per 100,000 hospitalizations for risky alcohol use), resulting in a 25% decreased probability of alcoholic gastritis (aRR: 0.75 [0.66 to 0.85]; p-value <0.0001). Furthermore, dependent cannabis usage resulted in a lower prevalence of alcoholic gastritis when compared to both nondependent cannabis users (0.72 [0.52 to 0.99]) and to noncannabis users (0.56 [0.41 to 0.76]).

Conclusions: We reveal that risky alcohol drinking combined with cannabis use is associated with reduced prevalence of alcohol-associated gastritis in patients. Given increased cannabis legislation globally, understanding whether and how the specific ingredients in cannabis plant extract can be used in the treatment of alcoholic gastritis is paramount. In this regard, further molecular mechanistic studies are needed to delineate the mechanisms of our novel findings not only for alcoholic gastritis but also for gastritis from other causes.

Background: Attention-deficit/hyperactivity disorder (ADHD) is associated with greater heavy alcohol use and depressive symptoms in adulthood. Yet, few studies have investigated whether childhood ADHD predicts an increased association between heavy drinking and depression in adulthood when this co-occurrence becomes more common. We examined associations among heavy alcohol use and depression longitudinally from ages 21 to 29 and whether these associations differed for those with or without childhood ADHD, as well as for those with or without persistent ADHD in adulthood.

Methods: Data were from the Pittsburgh ADHD Longitudinal Study, a prospective cohort of children diagnosed with ADHD and demographically similar individuals without ADHD histories. ADHD symptoms in adulthood were self- and parent reported; depressive symptoms and frequency of drinking 5 or more drinks in a single drinking occasion were self-reported and measured at 5 time-points from ages 21 to 29. Depression and alcohol use were modeled in a multiple-group, parallel process longitudinal growth model.

Results: The slopes of heavy alcohol use and depression were significantly and positively associated from ages 25 to 29 but not at the younger ages. Although the strength of these associations did not differ by group (with or without ADHD, childhood or adulthood), the slopes of depression and heavy drinking at the older ages were highly variable and individuals with ADHD showed significantly faster growth in depression from ages 25 to 29.

Conclusions: Due to the strengthening association between heavy drinking and depression for adults in their late 20s, and increasing depression for adults with ADHD histories, individuals with ADHD may be at greater risk for co-occurring depression and binge drinking. Negative reinforcement-related alcohol use may strengthen as these individuals age toward the fourth decade of life. More rigorous testing of this possibility is warranted.

Background: Alcohol use disorder is characterized by compulsive alcohol intake, or drinking despite negative consequences. Previous studies have shown that female rodents have a heightened vulnerability to drug use across different stages of the addictive cycle, but no previous studies have studied females in a model of aversion-resistant alcohol intake. Here, we investigated sex differences in binge-like and aversion-resistant alcohol drinking in C57BL/6J mice using a modified drinking-in-the-dark (DID) paradigm.

Methods: In Experiment 1, 24-hour aversion to quinine (0, 100, or 250 μM) was assessed. In Experiment 2, male and female adult C57BL/6J mice consumed 15% ethanol (EtOH) or water in a 2-bottle limited-access DID paradigm for 2 h/d for 15 days. The EtOH was next adulterated with quinine (0, 100, or 250 μM) over 3 consecutive drinking sessions to test aversion-resistant intake. In Experiment 3, intake of quinine-adulterated (100 μM) EtOH was assessed across all 15 drinking sessions.

Results: Quinine was equally aversive to both sexes in Experiment 1. In Experiment 2, female mice consumed significantly more alcohol than male mice during the final 6 drinking sessions. Levels of aversion-resistant intake did not differ between the sexes. In Experiment 3, quinine suppressed consumption in all mice, though females drank significantly more on the final 2 sessions.

Conclusions: The results of this study demonstrate that while female mice escalate and consume more EtOH than males, both sexes exhibit similar levels of aversion-resistant drinking. These results inform our understanding of how sex interacts with vulnerability for addiction and argue for the inclusion of females in more studies of aversion-resistant alcohol drinking.

Background: The Approach and Avoidance of Alcohol Questionnaire (AAAQ) was developed as a measure of craving to assess both desires to consume and desires to avoid consuming alcohol. Although the measure has been used in a variety of populations to predict future alcohol use behavior, the factor structures observed vary based on sample type (e.g., clinical vs. college samples) and may be overly long for use in repeated measures designs. The current article describes the development of a brief version of the AAAQ for use in clinical populations.

Methods: Using existing data sets of individuals in treatment for alcohol use disorder, exploratory analyses (e.g., exploratory factor analysis and item response theory) were conducted using an inpatient sample (N = 298) at a substance abuse treatment facility. Confirmatory analyses (e.g., confirmatory factor analysis and multiple regression) were conducted using an inpatient detoxification sample (N = 175) and a longitudinal outpatient treatment sample (N = 53).

Results: The brief AAAQ had comparable internal consistency, explained a similar amount of variance in alcohol consumption and related problems, and exhibited superior model fit as compared to the original measure.

Conclusions: These findings indicate that the brief AAAQ is an effective tool to assess alcohol craving in clinical populations in treatment settings.

Background: Alcohol use disorder is a major societal and individual burden that exacerbates health outcomes, decreases quality of life, and negatively affects U.S. healthcare spending. Although pharmacological treatments are available for alcohol use disorder, many of them are limited by small effect sizes and used infrequently. Citicoline is a widely available over-the-counter supplement with a favorable side effect profile. It acts through cholinergic pathways and phospholipid metabolism. The current report examines the effect of oral citicoline on alcohol use, craving, depressive symptoms, and cognitive outcomes in individuals with alcohol use disorder.

Methods: A 12-week, randomized, double-blind, parallel-group, placebo-controlled, pilot study of citicoline (titrated to 2,000 mg/d) in 62 adults (age 18 to 75) with alcohol use disorder was conducted. Alcohol use, such as number of drinking days, amount used, and number of heavy drinking days, was assessed using the Timeline Followback method and liver enzymes, while alcohol craving was measured using the Penn Alcohol Craving Scale. A neurocognitive battery (e.g., Rey Auditory Verbal Learning Test) and depressive symptoms scale (e.g., Inventory of Depressive Symptomatology Self-Report) scores were also collected. Data were analyzed using a random regression analysis.

Results: The primary outcome analysis was conducted in the intent-to-treat sample and consisted of 55 participants (78.2% men and 21.8% women, mean age of 46.47 ± 9.15 years). In the assessment period, the drinking days, on average, represented 77% of the assessed days. Significant between-group differences were not observed on alcohol use, craving, and cognitive or depressive symptom measures. Citicoline was well tolerated.

Conclusions: This proof-of-concept study observed that citicoline was well tolerated, but was not associated with a reduction in alcohol use or other outcomes, as compared to placebo. The favorable effects reported with citicoline for cocaine use, cognitive disorders, and other conditions do not appear to extend to alcohol use disorder.

Background: Survey-based estimates of the prevalence of alcohol abuse, dependence, and disorders in the United States rely upon self-reports of drinking patterns (e.g., binge drinking), social problems (e.g., trouble at work), physiological responses to use (e.g., tolerance), and desistance from use (e.g., withdrawal). Diagnostic criteria derived from these reports enable prevalence estimates of abuse and dependence, but moderating structural relationships among symptom groups may lead some light and moderate drinkers to appear to exhibit an alcohol use disorder (AUD).

Methods: A dynamic model of drinking and problems predicts that symptoms of dependence will moderate relationships between drinking measures and symptoms of abuse. Wave 1 National Epidemiologic Survey on Alcohol and Related Conditions data on DSM-IV diagnoses of abuse and dependence were used to test predictions from this model and assess whether moderating effects were observed among lighter and heavier drinkers (those who drink 1 to 3 vs. 4 or more drinks on average). A dose-response model that accounts for other known sources of risk heterogeneity related to drinking and problems enabled us to test these predictions.

Results: As expected from previous work, symptoms of abuse and dependence and dependence criteria were nonlinearly related to drinking patterns; more symptom reports appeared and criteria were met among less frequent drinkers who drank more on each occasion and this pattern of dose-response was substantially moderated among heavier drinkers. Controlling for these effects, relationships between drinking and symptoms of abuse were moderated among respondents who met more dependence criteria. These effects were observed among both lighter and heavier drinkers.

Conclusions: Moderating relationships observed between measures of drinking, abuse, and dependence criteria among lighter and heavier drinkers suggest that the same etiologic forces are at play among all drinking groups. Greater symptoms of dependence among lighter drinkers may lead to greater reports of symptoms of abuse and an AUD diagnosis.

Background: The burden of alcohol-associated cirrhosis (AC) is high, and though alcohol cessation improves mortality, many patients fail to engage in alcohol use disorder (AUD) treatment and continue drinking. Our aim was to determine rates, predictors, and outcomes of AUD treatment utilization in AC patients with private insurance.

Methods: We collected data from persons with AC (diagnosed by ICD-9/ICD-10 codes), aged 18 to 64 years, enrolled in the Truven MarketScan Commercial Claims and Encounters database (2009 to 2016). We determined rates and predictors of substance abuse treatment visits as well as rates of alcohol relapse prevention medication prescriptions, weighted to the national employer-sponsored insured population. Effects of AUD treatment utilization on decompensation rates were calculated using proportional hazards regression with propensity score adjustment.

Results: A total of 66,053 AC patients were identified, 32% were female, and mean age at diagnosis was 54.5 years. About 72% had insurance coverage for substance abuse treatment. Overall, AUD treatment utilization rates were low, with only 10% receiving a face-to-face mental health or substance abuse visit and only 0.8% receiving a Food and Drug Administration (FDA)-approved relapse prevention medication within 1 year of index diagnosis. Women were less likely to receive a face-to-face visit (hazard ratio [HR] 0.84, p < 0.001) or an FDA-approved relapse prevention medication (0.89, p = 0.05) than men. AC patients who had a clinic visit for AUD treatment or used FDA-approved relapse medication showed decreased risk of decompensation at 1 year (HR 0.85, p < 0.001 for either).

Conclusions: AUD treatment utilization is associated with lower decompensation rates among privately insured patients with AC. Women were less likely to utilize AUD treatment visits. Efforts to reduce gender-specific barriers to treatment are urgently needed to improve outcomes.