Alcoholism and pathways to recovery: new survey results on views and treatment options

Almost 19 million Americans require treatment for an "alcohol problem"; however, only 2.4 million have been diagnosed and just 139,000 receive medication to treat it. Chronic heavy drinking contributes to cardiovascular illnesses, liver disease, cancer, and psychiatric disorders. Imaging studies demonstrate structural changes in the human brain with prolonged exposure to alcohol. Alcoholism can thus be described as an acquired brain dysfunction with specific neurochemical and neuroanatomic pathways. There is a need to intervene early because the average age of alcohol experimentation is 11-13 years--delaying onset reduces the rate of alcoholism. A survey sponsored by the Community Anti-Drug Coalitions of America (CADCA) set out to measure the attitudes and misperceptions of 1000 adults from the general population plus 300 physicians and 503 individuals in recovery from alcohol use disorder (AUD) to better understand approaches toward alcohol treatment. In these surveys, 74% of the general public indicated that alcoholism affects their daily lives, with 41% reporting having to encourage a loved one to seek help for an alcohol problem. The vast majority (= 80%) indicated a stigma toward alcoholics. Denial or refusal to admit severity and fear of social embarrassment were the top 2 reasons for not seeking help. The majority of the general population believes that alcoholism is caused partly by moral weakness. The survey revealed that most Americans are open to medications to treat alcoholism if physician-recommended and if it could reduce alcohol cravings and maintain abstinence. In the past 55 years, only 3 medications (disulfiram, naltrexone, and acamprosate) have been US Food and Drug Administration (FDA)-approved for the treatment of AUD, each with unique mechanisms of action.     

Effect of alcohol on urinary and blood dolichols.

Alcohol appears to affect dolichol metabolism, as both serum and urinary dolichol concentrations were found to be significantly higher in alcoholics than in social drinkers. Furthermore, acute heavy drinking (5.5 g alcohol/kg body weight during 42 h) increased urinary dolichol excretion significantly, whereas moderate drinking (60 g/day for 10 days) had no effect. Increased urinary dolichol concentrations in alcoholics returned rapidly to normal with a half-life decay of 3 days, whereas increased serum dolichol concentrations did not change during a 7-day observation period. The mechanism behind alcohol-induced alterations in dolichol metabolism remains unclear, but based on our results, it seems likely that serum and urinary dolichols are regulated independently from each other.     

Increased GH responsiveness to dopamine receptor stimulation in alcohol addicts during the late withdrawal syndrome

In humans the release of growth hormone (GH) elicited by dopamine (DA) and DA agonists may represent a reliable model to assess change in sensitivity of DA receptors. We now report that in chronic alcoholics, 4–7 days after the suspension of alcohol consumption, the increase of GH response to DA infusion was higher than that seen in non alcoholic volunteers. The specificity of this GH response to DA administration was demonstrated by the use of domperidone, a novel peripheral antagonist of DA receptors. These results suggest the development of hyper-responsiveness of DA receptors involved in the control of GH secretion in chronic alcoholics during the later phases of the “withdrawal syndrome”.     

Blood glucose in intoxicated chronic alcoholics.

Chronic alcoholics may present with hyperglycemia or hypoglycemia. Because alcohol induces glycogenolysis, chronic alcoholics usually have higher blood glucose values than do nonalcoholic subjects. In a prospective study of blood glucose concentration in 201 chronic alcoholics, blood alcohol concentration, sex, weight, type of beverage consumed and time since last eating were not generally associated with lower blood glucose values. The infrequency of hypoglycemia in ambulatory chronic alcoholics may reflect the relatively ready availability of hostels, detoxification centres and hospitals in large cities. It is, however, important to be aware of the possible occurrence of hypoglycemia in chronic alcoholics, particularly when community facilities for the chronic alcoholic are not available.     

Synthesis and degradation of fatty acid ethyl esters by cultured hepatoma cells exposed to ethanol

Fatty acid ethyl esters are a family of neutral lipids that are the products of esterification of fatty acids with ethanol. Unlike other pathways of ethanol metabolism, ethyl esters are present in numerous human organs which are the targets of ethanol-induced damage. In the present study, we have shown that fatty acid ethyl esters are synthesized by a hepatoma cell line in tissue culture when exposed to ethanol concentrations easily attained by man during social drinking. Unlike alcohol dehydrogenase, the enzyme(s) responsible for synthesis of ethyl esters are membrane-bound and concentrated in the microsomal fraction of rat hepatocytes. In addition, fatty acid ethyl esters are hydrolyzed to free fatty acids and ethanol by membrane-bound enzyme(s) that are enriched in the microsomal and mitochondrial-lysosomal fractions. Intracellular hydrolysis of fatty acid ethyl esters release free fatty acids which are preferentially incorporated into cellular cholesterol esters. Thus, we have shown that a hepatocellular line exposed to concentrations of ethanol easily achieved in man by social drinking utilize endogenous fatty acids to form long-lived ethanol metabolites, fatty acid ethyl esters. Importantly, this family of neutral lipids may act as biochemical mediators of ethanol-induced cell damage, including the changes in cholesterol metabolism noted in chronic alcoholics.     

Toward a (Dys)functional Anthropology of Drinking: Ambivalence and the American Indian Experience with Alcohol

This article explores the complex and contradictory experiences of urban American Indian drinkers. While previous anthropological accounts have emphasized the functions served by American Indian drinking, the testimony of drinkers also documents their awareness of the destructive effects of heavy drinking, particularly the way in which it often interferes with their ability to meet social obligations. Nevertheless, people often continue to use alcohol, and this means that many are profoundly ambivalent about their drinking; they see it simultaneously as something that is embedded in certain important relationships, but also something that is destructive of much that they value. Drawing on interviews with 35 self-defined problem drinkers, this article details the ambiguous nature of the American Indian experience with alcohol, highlighting the need for clinically sophisticated anthropology of alcohol, [alcohol, American Indians, functional ism, clinical approaches]     

Alcoholism in the general hospital.

To assess the prevalence of alcoholism among people admitted to hospital 303 patients completed a drinking questionnaire. A total of 59 (19.5%) were found to have a drinking problem, which constituted a sixfold greater prevalence than recorded in a community survey using the same technique. The drinkers were mostly men and tended to be younger than the non-drinkers and to smoke more heavily, live in more crowded conditions, and be of lower social class. Significantly more of the drinkers had at least one parent who was an alcoholic. The results confirm that hospital inpatients comprise a larger proportion of alcoholics than found in the general population. Hence medical staff should be alert to such patients, so that treatment may be initiated at an early stage of social decompensation.     

Application of DNA microarrays to study human alcoholism

An emerging idea is that long-term alcohol abuse results in changes in gene expression in the brain and that these changes are responsible at least partly for alcohol tolerance, dependence and neurotoxicity. The overall goal of our research is to identify genes which are differentially expressed in the brains of well-characterized human alcoholics as compared with non-alcoholics. This should identify as-yet-unknown alcohol-responsive genes, and may well confirm changes in the expression of genes which have been delineated in animal models of alcohol abuse. Cases were carefully selected and samples pooled on the basis of relevant criteria; differential expression was monitored by microarray hybridization. The inherent diversity of human alcoholics can be exploited to identify genes associated with specific pathological processes, as well as to assess the effects of concomitant disease, severity of brain damage, drinking behavior, and factors such as gender and smoking history. Initial results show selective changes in gene expression in alcoholics; of particular importance is a coordinated reduction in genes coding for myelin components.     

Detection of an alcohol specific product in urine of alcoholics

A simple procedure, using high performance liquid chromatography, was developed to detect and measure in urine an alcohol specific product, "ASP" indicative of chronic alcohol consumption. One day after hospital admission, the average amount of ASP in urine of alcoholics was 17 times higher than that of control subjects and 5 and 2 times higher after 7 and 14 days of abstinence, respectively. Urinary levels of ASP should be of value in the identification of chronic alcoholism.     

Whisky,women and song: men,alcohol and AIDS in northern Thailand

Biomedical analyses are primarily concerned with the disinhibiting effects of alcohol and the consequent increased likelihood of engaging in high-risk sexual behavior. However, such an approach ignores indigenous constructions of drinking behavior and sexuality. In northern Thailand, alcohol drinking and sex with prostitutes are closely linked and both are crucial to the construction of the male identity. Sexual encounters with a commercial sex worker generally follow a period of preparatory drinking. It is common practice for laborers to celebrate their monthly receipt of wages by going out in large groups to feast and visit brothels. Solitary drinking is highly unusual given the connection of alcohol use and the manipulation of social relations. The marital and extramarital spheres are conceptualized, within this culture, as distinct arenas of sexual experience. Drinking and drunkenness serve as framing devices for men to make the transition from the structured, non-eroticized domestic sphere to the transgressive world of commercial sex and the affirmation of stereotypical masculinity it confers. Because of the link between alcohol consumption and commercial sex, as well as the high likelihood that drinkers either will refuse to use condoms or will use them incorrectly, social drinking in the northern Thailand context must be considered as a major risk factor for acquired immunodeficiency syndrome.     

Alcohol consumption by youth: Peers,parents, or prices?

Using data from the National Longitudinal Survey of Adolescent to Adult Health, we estimate the effect of peers’ alcohol consumption and alcohol prices on the drinking habits of high-school-age youth. We use the two-stage residual inclusion method to account for the endogeneity of peer drinking in nonlinear models. For our sample of high school students, we find that peer effects are statistically and economically significant regarding the choice to participate in drinking but are not significant for the frequency of drinking, including binge drinking. Regarding alcohol prices, even though we have good price variation in our sample, alcohol prices are not found to be significant. The results are important for policymakers who are considering policies to reduce underage drinking, as we conclude that no significant impact on underage drinking will result from low-tax states’ increasing excise taxes on alcohol so they are similar to those of high-tax states. Policymakers may choose to focus instead on the influence of peers and changing the social norm behavior.     

中枢单胺类神经递质在酒精依赖中的分子作用机制

酒精依赖是以失去控制地饮用酒精为特征的慢性、复发性脑疾病, 业已成为严重的社会问题。中枢单胺类神经递质(包括多巴胺、5-羟色胺等)在酒精依赖症的发生、发展和系统功能失调中发挥着重要作用。文章探讨了单胺类神经递质关键调控点多巴胺受体、5-羟色胺受体、转运体、酪氨酸羟化酶、色氨酸羟化酶及单胺氧化酶基因等在酒精依赖中的作用机制, 结合本实验室在基因敲除小鼠模型方面的研究进展提出了酒精依赖分子机制的研究策略。在系统评述中枢单胺类神经递质介导的酒精依赖分子作用机制的基础上, 结合本实验室在酪氨酸羟化酶激活剂钙调蛋白依赖的蛋白激酶Ⅱ方面的研究成果探讨了可用于酒精依赖症治疗的作用靶点, 提出通过调整基因调控区的甲基化程度和改变pre-mRNA的选择性剪切等表观遗传学策略预防和治疗酒精依赖症, 同时根据基因多态性研究结果提出对酒精依赖症患者进行个性化预防和治疗的新策略。     

Serum concentrations of interleukin-8 in relation to different levels of alcohol consumption

Serum levels of interleukin-8 (IL-8) are increased in patients with alcoholic hepatitis and correlate with disease severity. The present study was aimed at investigating serum IL-8 levels in relation to different levels of alcohol consumption. Serum IL-8 was measured in (a) 459 individuals randomly selected from the general adult population, including 221 alcohol abstainers, 140 light drinkers (1-140 g/week), 53 moderate drinkers (141-280 g/week), and 45 heavy drinkers (>280 g/week), as well as (b) 137 alcoholics admitted to the hospital. The proportion of individuals with abnormally high (>10 pg/mL) IL-8 levels increased with alcohol use from 5.9% in abstainers to 10.7% in light, 13.2% in moderate, and 17.8% in heavy drinkers (P=0.004). This proportion was exceedingly high in alcoholics admitted to the hospital (70.1%, P<0.001 with respect to all other categories). Extremely high (>100 pg/mL) IL-8 levels were only observed among alcoholics, and were more frequent in females than in males (23.5% versus 9.7%, P=0.03) in spite of lower alcohol consumption among the former. These data indicate that the effect of alcohol on serum IL-8 levels begins with light-to-moderate drinking and is dose-dependent. Females may be more prone than males to develop extremely high IL-8 levels after heavy alcohol intake.     

The role of early life experience and species differences in alcohol intake in microtine rodents

Social relationships have important effects on alcohol drinking. There are conflicting reports, however, about whether early-life family structure plays an important role in moderating alcohol use in humans. We have previously modeled social facilitation of alcohol drinking in peers in socially monogamous prairie voles. We have also modeled the effects of family structure on the development of adult social and emotional behaviors. Here we assessed whether alcohol intake would differ in prairie voles reared by both parents compared to those reared by a single mother. We also assessed whether meadow voles, a closely related species that do not form lasting reproductive partnerships, would differ in alcohol drinking or in the effect of social influence on drinking. Prairie voles were reared either bi-parentally (BP) or by a single mother (SM). BP- and SM-reared adult prairie voles and BP-reared adult meadow voles were given limited access to a choice between alcohol (10%) and water over four days and assessed for drinking behavior in social and non-social drinking environments. While alcohol preference was not different between species, meadow voles drank significantly lower doses than prairie voles. Meadow voles also had significantly higher blood ethanol concentrations than prairie voles after receiving the same dose, suggesting differences in ethanol metabolism. Both species, regardless of rearing condition, consumed more alcohol in the social drinking condition than the non-social condition. Early life family structure did not significantly affect any measure. Greater drinking in the social condition indicates that alcohol intake is influenced similarly in both species by the presence of a peer. While the ability of prairie voles to model humans may be limited, the lack of differences in alcohol drinking in BP- and SM-reared prairie voles lends biological support to human studies demonstrating no effect of single-parenting on alcohol abuse.     

Colonic microbiome is altered in alcoholism

Several studies indicate the importance of colonic microbiota in metabolic and inflammatory disorders and importance of diet on microbiota composition. The effects of alcohol, one of the prominent components of diet, on colonic bacterial composition is largely unknown. Mounting evidence suggests that gut-derived bacterial endotoxins are cofactors for alcohol-induced tissue injury and organ failure like alcoholic liver disease (ALD) that only occur in a subset of alcoholics. We hypothesized that chronic alcohol consumption results in alterations of the gut microbiome in a subgroup of alcoholics, and this may be responsible for the observed inflammatory state and endotoxemia in alcoholics. Thus we interrogated the mucosa-associated colonic microbiome in 48 alcoholics with and without ALD as well as 18 healthy subjects. Colonic biopsy samples from subjects were analyzed for microbiota composition using length heterogeneity PCR fingerprinting and multitag pyrosequencing. A subgroup of alcoholics have an altered colonic microbiome (dysbiosis). The alcoholics with dysbiosis had lower median abundances of Bacteroidetes and higher ones of Proteobacteria. The observed alterations appear to correlate with high levels of serum endotoxin in a subset of the samples. Network topology analysis indicated that alcohol use is correlated with decreased connectivity of the microbial network, and this alteration is seen even after an extended period of sobriety. We show that the colonic mucosa-associated bacterial microbiome is altered in a subset of alcoholics. The altered microbiota composition is persistent and correlates with endotoxemia in a subgroup of alcoholics.     

Factors Associated with Problem Drinking among Women Employed in Food and Recreational Facilities in Northern Tanzania

Background

There is growing evidence that alcohol consumption is associated with increased risk of HIV infection. To determine factors associated with problem drinking, we analyzed data collected in two prospective cohorts of at-risk female food and recreational facility workers in northern Tanzania.

Methods

We enrolled HIV seronegative women aged 18–44 years and employed in the towns of Geita, Kahama, Moshi, and Shinyanga. At enrolment, women were interviewed to obtain information about alcohol use, using CAGE and AUDIT screening scales, and risk factors for HIV infection. Blood and genital samples were collected for detection of HIV and sexually transmitted infections (STIs). We characterized alcohol use, concordance, and agreement of the scales, and examined the associations between characteristics of participants and problem drinking as defined by both scales using logistic regression. Lastly, we assessed problem drinking as a risk factor for recent sexual behavior and prevalent STIs.

Results

Among enrollees, 68% women reported ever drinking alcohol; of these 76% reported drinking alcohol in the past 12 months. The prevalence of problem drinking was 20% using CAGE and 13% using AUDIT. Overall concordance between the scales was 75.0% with a Kappa statistic of 0.58. After adjusting for age, independent factors associated with problem drinking, on both scales, were marital status, occupation, facility type, increasing number of lifetime sexual partners, and transactional sex in the past 12 months. In addition, women who were problem drinkers on either scale were more likely to report having ≥1 sexual partner (CAGE: aOR = 1.56, 95% confidence interval, CI: 1.10–2.23; AUDIT: aOR = 2.00, 95% CI: 1.34–3.00) and transactional sex (CAGE: aOR = 1.79, 95% CI: 1.26–2.56; AUDIT: aOR = 1.51, 95% CI: 1.04–2.18), in the past 3 months.

Conclusion

These findings suggest that interventions to reduce problem drinking in this population may reduce high-risk sexual behaviors and contribute in lowering the risk of HIV infection.     

Correlates of Adult Binge Drinking: Evidence from a British Cohort

Objective

To investigate whether parental social class and cognitive ability in childhood, as well as social and psychological factors, particularly personality traits, are independently associated with binge drinking in 50 year old adults assessed in a longitudinal birth cohort study.

Method

17,415 babies born in Great Britain in 1958 and followed up at 11, 33, and 50 years of age. Their binge drinking alcohol abuse at aged 50 was the outcome measure.

Results

6,478 participants with data on parental social class, childhood cognitive ability, educational qualifications at age 33, personality traits, psychological distress, occupational levels, and alcohol consumption (all measured at age 50) were included in the study. Using logistic regression analyses, results showed that parental social class, childhood intelligence, educational qualifications, occupational levels, personality traits (Extraversion and Disagreeableness), as well as psychological distress, were all significantly and independently associated with adult excessive alcohol use. Men tended to binge drink more than women (22% in men and 9.8% in women).

Conclusion

Both social and psychological factors influence adult excessive alcohol consumption. Personality traits play a more important role than previously understood. There appears to be a distinction between the frequency and dose level of alcohol consumption.     

Comparison of Self-Reported Alcohol Consumption to Phosphatidylethanol Measurement among HIV-Infected Patients Initiating Antiretroviral Treatment in Southwestern Uganda

Background

Alcohol consumption among HIV-infected patients may accelerate HIV disease progression or reduce antiretroviral therapy adherence. Self-reported alcohol use is frequently under-reported due to social desirability and recall bias. The aim of this study was to compare self-reported alcohol consumption to phosphatidylethanol (PEth), a biomarker of alcohol consumption, and to estimate the correlation between multiple measures of self-reported alcohol consumption with PEth.

Methods

The Uganda AIDS Rural Treatment Outcomes (UARTO) cohort is located in southwestern Uganda and follows patients on ART to measure treatment outcomes. Patients complete standardized questionnaires quarterly including questions on demographics, health status and alcohol consumption. Baseline dried blood spots (DBS) were collected and retrieved to measure PEth.

Results

One hundred fifty samples were tested, and 56 (37.3%) were PEth positive (≥8 ng/mL). Of those, 51.7% did not report alcohol use in the past month. Men were more likely to under-report compared to women, OR 2.9, 95% CI = 1.26, 6.65) and those in the higher economic asset categories were less likely to under-report compared to those in the lowest category (OR = 0.41 95% CI: 0.17, 0.94). Among self-reported drinkers (n = 31), PEth was highly correlated with the total number of drinking days in the last 30 (Spearman R = 0.73, p<0.001).

Conclusions

Approximately half of HIV infected patients initiating ART and consuming alcohol under-report their use of alcohol. Given the high prevalence, clinicians should assess all patients for alcohol use with more attention to males and those in lower economic asset categories who deny alcohol use. Among those reporting current drinking, self-reported drinking days is a useful quantitative measure.     

Hidden alcoholics

"Hidden alcoholics"-those who drink surreptitiously to keep their addiction secret-far out-number the overt habitues of skid rows. The former rather than the latter should be considered "typical" alcoholics. Even though they have severe problems, they maintain fairly good employment stability and stability in marriage. Yet they steadily deteriorate. Often "hidden" alcoholics go to physicians because of symptoms referable to alcoholism but contrive to conceal their addiction and so make diagnosis difficult. Hence, physicians observing certain kinds of symptoms that cannot be attributed to a readily observable or demonstrable pathologic change should make searching inquiry as to the patient's drinking habits. For not until the proper diagnosis is made in such cases can there be hope of effective treatment.     

Brain Docosahexaenoic Acid [DHA] Incorporation and Blood Flow Are Increased in Chronic Alcoholics: A Positron Emission Tomography Study Corrected for Cerebral Atrophy

Objective

Chronic alcohol dependence has been associated with disturbed behavior, cerebral atrophy and a low plasma concentration of docosahexaenoic acid (DHA, 22∶6n-3), particularly if liver disease is present. In animal models, excessive alcohol consumption is reported to reduce brain DHA concentration, suggesting disturbed brain DHA metabolism. We hypothesized that brain DHA metabolism also is abnormal in chronic alcoholics.

Methods

We compared 15 non-smoking chronic alcoholics, studied within 7 days of their last drink, with 22 non-smoking healthy controls. Using published neuroimaging methods with positron emission tomography (PET), we measured regional coefficients (K*) and rates (J_in) of DHA incorporation from plasma into the brain of each group using [1-¹¹C]DHA, and regional cerebral blood flow (rCBF) using [¹⁵O]water. Data were partial volume error corrected for brain atrophy. Plasma unesterified DHA concentration also was quantified.

Results

Mean K* for DHA was significantly and widely elevated by 10–20%, and rCBF was elevated by 7%–34%, in alcoholics compared with controls. Unesterified plasma DHA did not differ significantly between groups nor did whole brain J_in, the product of K* and unesterified plasma DHA concentration.

Discussion

Significantly higher values of K* for DHA in alcoholics indicate increased brain avidity for DHA, thus a brain DHA metabolic deficit vis-à-vis plasma DHA availability. Higher rCBF in alcoholics suggests increased energy consumption. These changes may reflect a hypermetabolic state related to early alcohol withdrawal, or a general brain metabolic change in chronic alcoholics.