Alcoholism, craving, and hormones: the role of leptin, ghrelin, prolactin, and the pro-opiomelanocortin system in modulating ethanol intake.

Evidence is growing that appetite regulating peptides such as leptin and ghrelin, but also other hormones including prolactin are altered in alcoholism. The brain pro-opiomelanocortin (POMC) system which has important mediating roles in alcohol intake also has important functions in prolactin regulation and energy homeostasis. Furthermore, it has been demonstrated to be functionally integrated with leptin regulation. The satiety factor leptin seems to be counteracted by the gut-derived peptide ghrelin which increases hunger and food intake. Consequently, the POMC system may have a role in integrating regulation of alcohol effects and these seemingly disparate regulatory systems. The goal of this mini-review is to discuss the results of some recent investigations of the potential interactions of these systems with acute and chronic alcohol responses.

Phosphatidylethanol as a sensitive and specific biomarker: comparison with gamma-glutamyl transpeptidase, mean corpuscular volume and carbohydrate-deficient transferrin.

Phosphatidylethanol (PEth), a direct ethanol metabolite, is detectable in blood for more than 2 weeks after sustained ethanol intake. Our aim was to assess the usefulness of PEth [comparing sensitivity, specificity and the area under the curve (AUC)] as compared with carbohydrate-deficient transferrin (CDT), gamma-glutamyl transpeptidase (GGT) and mean corpuscular volume (MCV), calculating the results from sober patients against those from alcohol-dependent patients during withdrawal. Fifty-six alcohol-dependent patients (ICD-10 F 10.25) in detoxification, age 43 years, GGT 81 U/l, MCV 96.4 fl, %CDT 4.2, 1400 g ethanol intake in the last 7 days (median), were included in the study. Over the time of 1 year, 52 samples from 35 sober forensic psychiatric addicted in-patients [age 34 years, GGT 16 U/l, MCV 91 fl, CDT 0.5 (median)] in a closed ward were drawn and used for comparison . PEth was measured in heparinized whole blood with a high-performance liquid chromatography method. GGT, MCV and %CDT were measured using routine methods. A receiver operating characteristic curve analysis was carried out, with 'current drinking status' (sober/drinking) as the state variable and PEth, MCV, GGT and CDT as test variables. The resulting AUC was 0.974 (P < 0.0001, confidence interval 0.932-1.016) for PEth. At a cut-off of 0.36 micromol/l, the sensitivity was 94.5% and specificity 100%. The AUC for CDT, GGT and MCV were 0.931, 0.894 and 0.883, respectively. A significant Spearman's rank correlation was found between PEth and GGT (r = 0.739), CDT (r = 0.643), MVC (r = 0.639) and grams of ethanol consumed in the last 7 days (r = 0.802). Our data suggest that PEth has potential to be a sensitive and specific biomarker, having been found in previous studies to indicate longer lasting intake of higher amounts of alcohol.

Exclusion of trisialo-transferrin from carbohydrate-deficient transferrin measurement: advantage in patients with chronic liver disease?

BACKGROUND: Biological markers for chronic alcohol consumption like MCV or gammaGT or carbohydrate deficient transferrin (CDT) are useful, but far from being perfect. In patients with liver disease a reliable marker for chronic alcohol consumption as the underlying etiology is highly needed. Recently, a new ELISA based version of the carbohydrate-deficient-transferrin (CDT-TRISIALO (-)) assay has been developed, which measures asialo-, monosialo- and disialo transferrin, but excludes trisialo- transferrin; that modification suggests higher sensitivity and specificity in detecting recent alcohol consumption in patients. AIMS: The study goal was to evaluate the sensitivity, specificity, positive and negative predicitive value of this new carbohydrate-deficient-transferrin assay (CDT-TRISIALO (-)) in a group of patients with liver disease and to compare the results with that of the established CDT assay (CDT-TRISIALO (+)). PATIENTS AND METHODS: Our study population consisted of 110 consecutive patients (male: n = 80 [72.7 %], female: n = 30 [27.3 %]) with liver disease of the following etiologies: chronic alcohol consumption (n = 51 [46.4 %]; Out of them 30 alcohol abusing patients were assessed by cage = 1 and 21 alcohol dependent patients were assessed by cage = 2, chronic viral hepatitis (n = 33 [30.0 %]) including 25 [22.7 %] patients with chronic hepatitis C infection and 8 [7.3 %] patients with chronic hepatitis B infection), haemochromatosis (n = 4 [3.6 %]), mechanical cholestasis (n = 17 [15.5 %]) and other liver diseases (n = 5 [4.6 %] including autoimmune hepatitis (n = 2) and primary biliary cirrhosis (n = 3)). 27.3 % of our patients (n = 30) had no liver cirrhosis whereas the majority (72.7 %, n = 80) had liver cirrhosis. RESULTS: In our population of liver disease patients the CDT-TRISIALO (-) assay had a sensitivity of 72.7 % and specificity of 58.1 % for recent alcohol consumption at the published cutoff level of 2.6 %. The positive predictive value was 34.0 % and the negative predictive value was 87.8 %. Sensitivity and specificity of the CDT-TRISIALO (+) assay at the recommended cutoff level of 4.7 % were similar, 77.3 % and 49.3 %, respectively. The positive and negative predictive values were 30.9 % and 88.1 %. CDTTRISIALO (+) and CDT-TRISIALO (-) levels increased significantly with higher Child-Pugh stages. CONCLUSION: The newly developed carbohydrate deficient transferrin test (CDT-TRISIALO (-)) is of no advantage as compared to the established assay (CDT-TRISIALO (+)) when used in a patient population with liver disease. In that population, normal CDT-TRISIALO (-) helps to exclude recent alcohol consumption; this results from the high negative predictive value of a normal CDT-TRISIALO (-).

Epidemiology of substance use in a representative sample of 18-year-old males.

AIMS: To assess recent drug use through urine testing as well as the prevalence of tobacco and alcohol dependence among young males and to analyse the associations between tobacco dependence and cannabis use (delta-9-tetrahydrocannabinol, THC), tobacco dependence, and alcohol dependence as well as between THC use and other illicit drug use. METHODS: Urine samples were collected, and nicotine and alcohol questionnaires were administered. Carbon monoxide was assessed in exhaled air. Data from young males from representative, selected districts of Lower Austria were recorded during the annual physical examination for mandatory military service. Out of all 18-year-old males in Austria 3.8% (n = 1902) were included in the study. Prevalence of recent illicit drug use, tobacco dependence (heavy smoking index, HSI), alcohol dependence (The 4-item cutting down, annoyance by criticism, guilty feeling, and eye-openers (CAGE) questionnaire), and associations between substance categories by means of logistic regression analyses were calculated. RESULTS: Alcohol abuse was found in 15.1% and alcohol dependence was found in 3.2%. According to the HSI 51.5% of males reported daily smoking, of whom 43.7% showed a mild level, and 7.8% a high level, of nicotine dependence. About 5.1% of the sample evidenced THC in urine. Opiates were identified in 2.7% of urine samples. Smokers showed a higher risk of THC use. THC users had a tendency to use cocaine and amphetamines more frequently than THC abstainers. CONCLUSION: Nicotine and alcohol dependence is common among young males. Biological assessment of illicit drug use seems to confirm previous questionnaire-based findings of associations between THC use and other illicit drugs. Urine testing seems to be an adequate method to analyse associations of THC use and other illicit drugs. In combination with questionnaires urine testing may be used for the assessment of associations of tobacco dependence and recent illicit drug use based on epidemiological surveys.

Craving and other characteristics of the comorbidity of alcohol and nicotine dependence.

PURPOSE: In this cross-sectional study we compared alcohol-dependent smokers and non-alcohol-dependent smokers with respect to intensity of nicotine dependence, craving conditions, sleep disturbances, comorbidity with major depression, reasons for smoking, accompanying somatic diseases and patients' prolonged abstinence from smoking during the 3 years preceding the study. SUBJECTS AND METHODS: Fifty-one alcohol-dependent smokers and 327 non-alcohol-dependent smokers diagnosed as ICD-10 and DSM-IV-nicotine dependent, were investigated by means of the Fagerström Test for Nicotine Dependence, the Lübeck Craving-Recurrence Risk Questionnaire and the Lesch Alcohol Dependence Typology (both adapted to smoking). RESULTS: The intensity of nicotine dependence was more enhanced in alcohol-dependent smokers compared to non-alcohol-dependent smokers. Several variables of all factors of craving ("depressive mood", "stimulation", "relaxation", "socially triggered tension") were significantly increased in alcohol-dependent patients (P<0.05). Alcohol-dependent smokers showed depressive symptoms and sleep disturbances, whilst non-alcohol-dependent individuals mainly smoked for stress release and weight control. DISCUSSION: Our study demonstrates that the intensity of nicotine dependence, several conditions of craving for nicotine, sleep disturbances and symptoms of depression appear to be enhanced in alcohol-dependent smokers compared with non-alcohol-dependent smokers. Conclusions. - It is hoped that the factors of craving and reasons for smoking identified in this study will contribute to a better understanding of smoking temptation in alcohol-dependent smokers and non-alcohol-dependent smokers in future.

CDT values are not influenced by epithelial cell apoptosis in chronic alcoholic patients-preliminary results.

Carbohydrate-deficient transferrin (CDT) has been well established as a marker for high alcohol consumption. As studies concerning the specificity of CDT in patients with liver disease have shown controversial outcomes, efforts to illuminate mechanisms leading to impaired CDT specificity in this patient group cannot yet be considered successful. Evidence of apoptosis as examined in 72 alcohol-dependent patients using serum contents of caspase-related M30 monoclonal antibody significantly correlated with aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase but did not influence CDT levels. These results suggest that impairment of CDT specificity is brought forth by derangement of hepatic metabolism rather than by acute hepatocellular damage.

The Austrian multicentre study on smoking: subgroups of nicotine dependence and their craving.

BACKGROUND: The misconception of tobacco smoking as a 'bad habit' has been replaced by a diagnosis of addiction. Although help to quit is offered by nicotine replacement, antidepressants and psychotherapeutic support, there is no cure yet. One cause of impediment might be psychiatric comorbidity. Therefore, we searched for smoker subgroups, needing different treatments. AIM OF THE STUDY: The study aimed at subtyping smokers in an attempt to better understand the phenomenon of resistant smokers and provide more information that could potentially become useful to treatment centres assuming the subtypes correlate directly with outcomes of different smoking cessation treatments, tailor-made according to subtypes. METHODS: 330 out of 430 recruited smokers were classified as nicotine dependent (ICD-10) and tobacco dependent (DSM-IV) and remained in the study. They were investigated with different diagnostic assessments: Fagerström Test (FT), Lübeck Craving Risk Relapse Questionnaire and Lesch Typology Questionnaire (the last two being modified for smoking). RESULTS: Dependence severity degree is reflected by the FT. FT scores >/=5 indicated higher conspicuousness. Four clusters for nicotine craving were found: (1) 'depressed', (2) 'stimulated', (3) 'relaxed mood state' and (4) 'socially triggered tensed mood'. In contrast to alcoholism, 'stimulation' was one of the major craving conditions in smokers. The decision tree, consisting of the FT and the Lesch Typology Questionnaire, distinguishes four subgroups of nicotine-dependent persons. CONCLUSION: The subgroups reflect different reinforcement and psychosocial disturbances. They match treatment and can be applied as outcome predictors in controlled treatment and relapse prevention studies.