Otto M. Lesch

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 µmol/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.

Phosphatidylethanol: normalization during detoxification, gender aspects and correlation with other biomarkers and self-reports.

Phosphatidylethanol (PEth) is a direct ethanol metabolite, and has recently attracted attention as biomarker of ethanol intake. The aims of the current study are: (1) to characterize the normalization time of PEth in larger samples than previously conducted; (2) to elucidate potential gender differences; and (3) to report the correlation of PEth with other biomarkers and self‐reported alcohol consumption. Fifty‐seven alcohol‐dependent patients (ICD 10 F 10.25; 9 females, 48 males) entering medical detoxification at three study sites were enrolled. The study sample was comprised of 48 males and 9 females, with mean age 43.5. Mean gamma glutamyl transpeptidase (GGT) was 209.61 U/l, average mean corpuscular volume (MCV) was 97.35 fl, mean carbohydrate deficient transferrin (%CDT) was 8.68, and mean total ethanol intake in the last 7 days was 1653 g. PEth was measured in heparinized whole blood with a high‐pressure liquid chromatography method, while GGT, MCV and %CDT were measured using routine methods. PEth levels at day 1 of detoxification ranged between 0.63 and 26.95 µmol/l (6.22 mean, 4.70 median, SD 4.97). There were no false negatives at day 1. Sensitivities for the other biomarkers were 40.4% for MCV, 73.1% for GGT and 69.2% for %CDT, respectively. No gender differences were found for PEth levels at any time point. Our data suggest that PEth is (1) a suitable intermediate term marker of ethanol intake in both sexes; and (2) sensitivity is extraordinary high in alcohol dependent patients. The results add further evidence to the data that suggest that PEth has potential as a candidate for a sensitive and specific biomarker, which reflects longer‐lasting intake of higher amounts of alcohol and seemingly has the above mentioned certain advantages over traditional biomarkers.

The Alcoholic Phenotypes among Different Multidimensional Typologies: Similarities and Their Classification Procedures

AIM This detailed cross-sectional analysis, obtained from a sample of alcohol-dependent patients, attempts to compare multiple methods that have been created to classify or subtype alcoholics. METHODS The sample comprised 318 alcohol-dependent patients recruited from the alcoholism unit (NETER) of the Psychiatric Service of Santa Maria University Hospital in Lisbon (Portugal). All subjects were evaluated during the outpatient therapeutical programme for operationalized criteria, reported by each alcoholism typology. RESULTS Regarding concordance agreement (kappa values) for the three type I/II classifications, von Knorring versus Sullivan yielded the higher rate of agreement, followed by von Knorring versus Gilligan and Gilligan versus Sullivan criteria. Chi-square comparisons showed a significant overlap between Babor type A and Cloninger type I of von Knorring and Sullivan. Over-two-type classifications showed the following significant positive relations: Lesch type I versus NETER heredopathic subtype; Lesch type II versus NETER anxiopathic subtype and Babor type A; Lesch type III versus NETER tymopathic subtype; Lesch type IV versus Cloninger type II of von Knorring and Sullivan criteria; and NETER adictopathic subtype versus Cloninger type II of von Knorring, Sullivan and Gilligan criteria. CONCLUSIONS There is a significant overlap across many of the multivariate alcoholic subtypes purposed, in which much of the concordance is a function of common characteristics in subtype operationalization. Commonalities among these different subtyping classification systems offers the possibility of identifying important dimensions that better differentiate individuals among problem drinkers populations.

Relationship between Substance Use and Body Mass Index in Young Males

Recent findings in basic scientific research, such as neurobiological and neuroimaging studies, have suggested common pathways for food and drug intake. It was hypothesized that both compete for the same brain reward sites, and that a higher body mass index (BMI) may be associated with lower substance use. The aim of this study was to investigate the relationship between BMI and substance use in a large sample of young male adults. The sample consisted of 1,902 18-year-old males from a province of Austria in a naturalistic cross-sectional setting. Questionnaires were administered to assess alcohol abuse and dependence (CAGE) and nicotine dependence (Heavy Smoking Index). Urine samples were collected to assess the prevalence of recent illicit drug use. Associations between BMI and substance use were calculated by means of logistic regression analyses. An inverse relationship between BMI and recent illicit drug use was found. This relationship remained significant after adjusting for possible confounding factors such as level of education, nicotine dependence, breath carbon monoxide (CO) levels, and alcohol abuse and dependence. No significant association was found between BMI and nicotine and alcohol dependence. A higher BMI was associated with lower illicit drug use in our sample of young adult males. These results provide further evidence for the hypothesis that food and drugs may compete for the same brain reward sites. 

Multiple substance use among young males

Neurobiological studies hypothesize a common final pathway of addictive behavior in the mesolimbic dopaminergic system. Nicotine has been shown to sensitize the reward pathway, thereby causing increased drug-seeking behavior. Since there is evidence to suggest that nicotine, alcohol and other psychoactive substances act on the same final pathway and seem to augment their effects in animal subjects, drug intake behavior of humans would likely be reflected in increased substance use of nicotine-dependent persons. We used biological markers of substance use as well as questionnaires to assess the levels of psychoactive substance use among 18-year-old males in a naturalistic cross-sectional setting. We found that increasing levels of nicotine dependence were related to higher levels of alcohol abuse and dependence. Furthermore, higher levels of nicotine dependence were associated with elevated levels of recent cannabinoid use.

Hypnotic catalepsy-induced changes of regional cerebral glucose metabolism

In an attempt to elucidate the physiological basis of hypnosis, we investigated the changes of whole-brain and regional cerebral glucose metabolism, from a state of resting wakefulness to a hypnotized state with whole-body catalepsy, using positron emission tomography and the 2[18F]fluorodeoxyglucose method in 15 highly hypnotizable adults. Neither the random order of study conditions nor any of the other experimental factors had a measurable effect, and there was no statistically significant global activation or metabolic depression. However, repeated measures analysis of variance revealed a statistically significant heterogeneity of symmetric regional responses: Mainly the occipital areas, including visual and paravisual cortex, became relatively deactivated, while some metabolic recruitment was found in structures involved in sensorimotor functions. The observed pattern of changes of regional cerebral activity corresponds with the shift of attention away from normal sensory input that hypnosis is known to produce.

Does breath carbon monoxide measure nicotine dependence

ABSTRACT The aim of the current study was the examination of exhaled breath carbon monoxide levels as a predictor for heaviness of smoking. In this regard, nicotine dependence was assessed among a representative sample of 1,870 Austrian male military conscripts in a cross-sectional setting. Participants completed the Heaviness of Smoking Index (a brief questionnaire for assessment of nicotine dependence), and their expired breath carbon monoxide levels were measured. The performance of carbon monoxide as a predictor of dependence levels was examined by means of Receiver-Operating-Characteristic Curve Analysis. Area Under the Curve, as well as sensitivity and specificity, were reported for each carbon monoxide cut-off level. The authors demonstrate that exhaled carbon monoxide levels serve as a satisfactory means to discriminate between smokers and non-smokers, yielding optimal discrimination at a cut-off level ⩾ 5.5 parts per million (ppm), with a sensitivity of 95% and a specificity of 83%. However, the results indicate that carbon monoxide levels do not discriminate adequately between different levels of severity of nicotine dependence. The study demonstrates exhaled carbon monoxide as a useful marker of smoking status but not of nicotine dependence.

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.

Serbian and Austrian Alcohol-Dependent Patients: A Comparison of Two Samples Regarding Therapeutically Relevant Clinical Features

AIMS To support the Serbian Expert Board in setting up reimbursement for modern pharmacotherapeutic support, we compared a Serbian sample of alcohol-dependent patients with an Austrian sample, in order to detect differences that might inhibit the introduction of anti-craving medications in Serbia. METHODS One hundred and twenty-seven (116 males) alcohol-dependent patients in Serbia and 136 in Austria (78 males) were enrolled consecutively from January 2011 to March 2012 and were assessed using the Lesch alcoholism typology instrument (LAT). RESULTS Age of onset was slightly higher in the Austrian sample (28.5 vs. 30.0; P = 0.10). The Serbian sample showed a higher rate of anxiety disorders than the Austrian sample (89.8 vs. 26.5%, P ≤ 0.0001). Suicidal tendencies, independent of alcohol intake or withdrawal syndrome, were higher in the Austrian sample (1.6 vs. 13.2% P ≤ 0.0001). There was no difference between the two samples in Lesch-Type IV (26 vs 28); there was a slight excess in the Serbian sample of Type I (15 vs. 10). In Austria, significantly more Type II patients (32 vs. 52) had been included, while the Serbian sample comprised significantly more Type III patients. CONCLUSIONS Austrian and Serbian patients are quite similar, without any showing any factor that would detract from the potential value of modern anti-craving medications in Serbia. The differences in anxiety disorders might be due to the 1990s war and should be investigated further.

Accessibility and Affordability of Alcohol Dependency Medical Care in Serbia

CONTEMPORARY HOT ISSUES ON ALCOHOL DEPENDENCY IN SERBIA Alcoholic beverages are traditional to the Balkans region since the Antiquity. Consumption of domestic honey-made spirits and wine was wide spread among the Serbs even in the early medieval history before spreading of Christianity (1). Today, it remains a deeply rooted custom while prevalence of full scale dependency and associated disorders in Serbia are slightly less frequent than European average (3.4 vs. 4.0% and 5.2 vs. 7.5%, respectively) Alcohol dependence in cited WHO sources was confirmed according to ICD-10 criteria. (2). Although hosting one of the oldest medical societies across European region, Serbia still lacks systematic morbidity and mortality registries for a variety of leading prosperity diseases including alcoholrelated disorders (3). Nevertheless some national estimates on standardized death rates attributed to alcohol-related causes and alcohol consumption are available thus allowing the insight into trends of change since late 1990s. Likewise, elsewhere in the European community, traffic accidents caused by alcohol consumption posed a substantial challenge to the road safety (4). Undisputed relationship between alcohol blood concentration and severity of acquired traffic injuries was proven in national forensic studies on cases with fatal outcome (5). Afterward, national policies have been adopted with more severe legislation framework and punitive measures compared to previous real socialism legacy (6). Unfortunately, like many other public health strategies, this one actually had quite limited effect to alcohol attributed traffic accident mortality in consecutive years (7). According to the forensic observation of a local sample of deceased with mortal injuries, craniocerebral trauma remains the most typical clinical pattern (8). Among direct alcohol effects on mortality are classified as mental disorders with suicidal tendency (9) as well as poisoning with ethanol, methanol, and unspecified alcoholic compounds, which were attributed a total of 248 fatal outcomes in 2012. Indirect alcohol effects on mortality present far more extensive burden for the health system. Diseases such as alcoholcaused degeneration of nervous system, alcoholic cardiomyopathy, alcoholic liver disease, and alcohol-induced chronic pancreatitis caused a total of 430 deaths in 2012 according to latest official release (10). Observing the landscape of age-stratified direct alcohol-related deaths due to overdoses, one could notice heavy domination of 45–79 years age group. According to the criminal justice procedure in Serbia, there are some 106 beds of Special Prison Hospital in Belgrade reserved for mandatory treatment of offenders who committed crimes in alcoholic condition. Such treatments are either been conducted in the penitentiary institution itself or elsewhere, in a specialized medical facility. Quite a peculiar issue is non-fatal alcohol overdoses whose treatment lies within responsibility of the National Poison Control Center of the Military Medical Academy being the reference institution in the country for diagnostics and treatment of intoxications. This facility reported 2078 patients admitted because of acute ethylalcohol intoxications or almost 50% of all cases in 2012 (11). Broad portion of similar clinical cases, with or without suicidal intention, are being admitted to the emergency wards of other tertiary university clinics across the countries. So far illicit psychoactive substances cause several fold less overdoses than alcohol although drugscaused mortality belongs to far younger adolescent age group (12). One promising trend among the youth is slightly decreasing prevalence of those who have ever used alcohol from 75.6% in 2008 to 64.3% level in 2012 (13). Risky attitudes of adolescents toward the alcohol use contributed substantially to the current morbidity (14). Recent pan-European trends expose binge drinking habits and co-assumption of diverse novel psychoactive substances, which contribute to the challenging nature of alcohol addiction treatment (15).