Alcoholism, clinical and experimental research最新文献

Background: Alcohol abuse and adherence to atherogenic diet (AD; a low-carbohydrate-high-protein diet) have been positively associated with cardiovascular disease. In addition, it has been demonstrated clinically that dietary intake is increased on days when alcohol is consumed. Here, the additive effects of ethanol (EtOH) and AD on atherosclerosis, a major underlying cause of cardiovascular disease, were investigated in apolipoprotein E/low-density lipoprotein receptor double-knockout (KO) mice. The mechanisms, especially aortic oxidative stress damage, were highlighted.

Methods: Twelve-week-old male KO mice on AD with or without EtOH treatment were bred for 4 months. Age-matched male C57BL/6J mice on a standard chow diet without EtOH treatment served as controls. Analyses were conducted using ultrasound biomicroscopy, histopathological and fluorescence immunohistochemical examinations, Western blots, and polymerase chain reaction.

Results: KO mice on AD with EtOH treatment showed increases in aortic maximum intima media thickness, hypoechoic plaque formation, and mean Oil-Red-O content. These results were associated with enhanced ratio of aortic 8-hydroxy-2'-deoxyguanosine (8-OHdG)-immunopositive area to the metallothionein (MT) immunopositive area and suppression of AD-induced up-regulated aortic Mt1, Mt2, and upstream stimulatory factor 1 mRNA expressions. Moreover, 8-OHdG was expressed in the nuclei of CD31- and alpha smooth muscle actin-immunopositive cells, and the up-regulated mRNA expressions of aortic nitric oxide synthase 3 and platelet-derived growth factors were only observed in the KO mice on AD with EtOH treatment.

Conclusions: Alcohol abuse and adherence to AD may promote the shift of aortic oxidative stress and antioxidative stress balance toward oxidative stress predominance and reduced antioxidative stress, which may be partly due to the decrease in MT at the cell biological level and down-regulation of Mt at the gene level, which in turn could play a role in the up-regulation of endothelial dysfunction-related and vascular smooth muscle cell proliferation-related gene expression and the progression of atherosclerosis in mice with hyperlipidemia.

Background: Gestational ethanol (EtOH) exposure is associated with multiple developmental abnormalities, collectively termed fetal alcohol spectrum disorder (FASD). While the majority of women abstain from EtOH following knowledge of pregnancy, one contributing factor to the high FASD prevalence is that pregnancy is not detected until 4 to 6 weeks. Thus, EtOH consumption continues during the initial stages of fetal development.

Methods: An experimental protocol is described in which rhesus macaques self-administer 1.5 g/kg/d EtOH (or isocaloric maltose dextrin) prior to pregnancy and through the first 60 days of a 168-day gestation term. Menstrual cycles were monitored, including measurements of circulating estradiol and progesterone levels. The latency to consume 1.5 g/kg EtOH and blood EtOH concentration (BEC) was measured.

Results: Twenty-eight fetuses (14 EtOH and 14 controls) were generated in this study. EtOH did not affect menstrual cycles or the probability of successful breeding. No EtOH-induced gross adverse effects on pregnancy were observed. Individual variability in latency to complete drinking translated into variability in BEC, measured 90 minutes following session start. Drinking latencies in controls and EtOH drinkers were longer in the second gestational month than in the first. All pregnancies reached the planned experimental time point of G85, G110, or G135, when in utero MRIs were performed, fetuses were delivered by caesarean section, and brains were evaluated with ex vivo procedures, including slice electrophysiology. Fetal tissues have been deposited to the Monkey Alcohol Tissue Research Resource.

Conclusions: This FASD model takes advantage of the similarities between humans and rhesus macaques in gestational length relative to brain development, as well as similarities in EtOH self-administration and metabolism. The daily 1.5 g/kg dose of EtOH through the first trimester does not influence pregnancy success rates. However, pregnancy influences drinking behavior during the second month of pregnancy. Future publications using this model will describe the effect of early-gestation EtOH exposure on anatomical and functional brain development at subsequent gestational ages.

Background: Studies of the role of alcohol use in diabetes risk have rarely included lifetime alcohol use measures, including the frequency of heavy occasions, or evaluated risks among Black or Hispanic respondents in US samples.

Methods: Data from the 2014 to 2015 National Alcohol Survey of the U.S. population were used to estimate diabetes risk from drinking patterns at the time of onset in Cox proportional hazards models in a retrospective cohort design. Models for the population, males and females, and for White, Black, and Hispanic respondents of both genders were estimated using 2 versions of drinking pattern groupings at each age.

Results: While a number of significant results were found with the first version of the drinking measures, we focus on those confirmed with measures from responses strictly prior to the age of risk estimation. Compared to the lifetime abstainer group, the "drinking at least weekly with less than monthly 5+" group had a significantly lower hazard ratio (HR) for the total sample (HR = 0.64) and among Whites (HR = 0.42). Significantly reduced risks were found in the same models for those who drank 5+ at least monthly but not weekly. No significantly elevated risks were found for either current or prior heavy occasion drinking.

Conclusions: These results are consistent with some prior studies in finding reduced risks for regular light-to-moderate drinkers, but not consistent with findings from other studies showing increased risk from heavy occasion drinking, particularly among women. New and larger studies with well-defined drinking pattern measures are needed, particularly for U.S. Blacks and Hispanics, to address varying results in this literature.

Background: Pancreatitis is an increasingly common clinical condition that causes significant morbidity and mortality. Cannabis use causes conflicting effects on pancreatitis development. We conducted a larger and more detailed assessment of the impact of cannabis use on pancreatitis.

Methods: We analyzed data from 2012 to 2014 of the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample discharge records of patients 18 years and older. We used the International Classification of Disease, Ninth Edition codes, to identify 3 populations: those with gallstones (379,125); abusive alcohol drinkers (762,356); and non-alcohol-non-gallstones users (15,255,464). Each study population was matched for cannabis use record by age, race, and gender, to records without cannabis use. The estimation of the adjusted odds ratio (aOR) of having acute and chronic pancreatitis (AP and CP) made use of conditional logistic models.

Results: Concomitant cannabis and abusive alcohol use were associated with reduced incidence of AP and CP (aOR: 0.50 [0.48 to 0.53] and 0.77 [0.71 to 0.84]). Strikingly, for individuals with gallstones, additional cannabis use did not impact the incidence of AP or CP. Among non-alcohol-non-gallstones users, cannabis use was associated with increased incidence of CP, but not AP (1.28 [1.14 to 1.44] and 0.93 [0.86 to 1.01]).

Conclusions: Our findings suggest a reduced incidence of only alcohol-associated pancreatitis with cannabis use.

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: 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.