Loss, gain and choice difficulty in gambling patients: Neural and behavioural processes.

Impaired decision-making is often displayed by individuals suffering from gambling disorder (GD). Since there are a variety of different phenomena influencing decision-making, we focused in this study on the effects of GD on neural and behavioural processes related to loss aversion and choice difficulty. Behavioural responses as well as brain images of 23 patients with GD and 20 controls were recorded while they completed a mixed gambles task, where they had to decide to either accept or reject gambles with different amounts of potential gain and loss. We found no behavioural loss aversion in either group and no group differences regarding loss and gain-related choice behaviour, but there was a weaker relation between choice difficulty and decision time in patients with GD. Similarly, we observed no group differences in processing of losses or gains, but choice difficulty was weaker associated with brain activity in the right anterior insula and anterior cingulate cortex in patients with GD. Our results showed for the first time the effects of GD on neural processes related to choice difficulty. In addition, our findings on choice difficulty give new insights on the psychopathology of GD and on neural processes related to impaired decision-making in GD.

German Guidelines on Screening, Diagnosis, and Treatment of Alcohol Use Disorders: Update 2021.

INTRODUCTION: Alcohol consumption in Germany is associated with considerable health and economic consequences. In addition to prevention, the early detection and differential treatment of those affected play an important role. The guideline "Screening, Diagnosis, and Treatment of Alcohol Use Disorders" forms the basis of this care for people suffering from alcohol use disorders. Regular updates integrate the current state of research evidence and clinical expertise. METHODS: Under the auspices of the German Society for Psychiatry, Psychotherapy, Psychosomatics, and Neurology and the German Society for Addiction Research and Addiction Therapy e.V. (DG-Sucht), the 2019-2020 S3 guideline on alcohol was revised by eight working groups. Thirty-five professional societies participated in a structured consensus process to deliberate the recommendations. Potential conflicts of interest were examined in advance, documented, and taken into account during the voting on the recommendations. RESULTS: The guideline provides recommendations on screening and brief interventions for different groups of people, as well as on treatment of individuals in the acute and post-acute phases of withdrawal. Special emphasis was placed on the treatment of comorbid somatic and psychological disorders. In addition, recommendations for specific groups of people (e.g., children and adolescents, pregnant women) have been made and adapted to the German care landscape.

Dysfunctional approach behavior triggered by alcohol-unrelated Pavlovian cues predicts long-term relapse in alcohol dependence.

We demonstrated that alcohol-dependent patients who relapsed within 1 year after detoxification showed stronger PIT effects compared with abstainers and controls. Relapsers particularly failed to correctly perform in trials where an instrumental stimulus required inhibition while a Pavlovian background cue indicated a monetary gain. Under that condition, relapsers approached the instrumental stimulus, independent of the expected punishment. The failure of inhibiting an aversive stimulus in favor of approaching an appetitive context cue reflects dysfunctional altered learning mechanisms in relapsers.

[Suicide and Suicide Prevention in Psychiatric Hospitals]. / Suizid und Suizidprävention im psychiatrischen Krankenhaus.

Suicide prevention is a central topic of psychiatry and psychotherapy. Times of changes in psychiatric inpatient treatment conceptions usually come along with an increase of psychopathology and with increasing suicide rates in psychiatric hospitals to, like seen in the seventies and eighties of last century in Germany. After a real increase of inpatient suicides during those years the number and rate of inpatient suicides decreased from about 280 of 100 000 admissions of patients in 1980 to about 50 in 2014. Young male schizophrenic patients were identified as the new high risk group despite the severely depressed patients with delusions as a traditional high risk group. Nowadays suicide prevention is part of all educational programs in psychiatry and psychotherapy.

Screening for Hazardous Drinking in Nursing Home Residents: Evaluating the Validity of the Current Cutoffs of the Alcohol Use Disorder Identification Test-Consumption Questions by Using Ethyl Glucuronide in Hair.

BACKGROUND: Because of physiological changes, elderly people are much more exposed to the adverse effects of alcohol. Therefore, hazardous drinking is defined at lower levels as compared to younger adults. This work aimed to evaluate the validity of the current cutoff levels of the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) questions to detect hazardous drinking in the elderly by using ethyl glucuronide in hair (HEtG). METHODS: In a border region between Austria and Germany, 344 nursing home residents were included from 33 of the 107 nursing homes. Residents were asked to answer the AUDIT-C questions, hair samples were obtained, and nursing staff members were asked for their assessments of the residents' alcohol consumption. Hair samples were analyzed for HEtG using gas chromatography-mass spectrometry. Receiver-operating characteristic (ROC) curve analysis was performed to determine the validity of cutoff values for the AUDIT-C to detect an alcohol consumption of ≥10 g of alcohol/d. RESULTS: A total of 11.3% of the nursing home residents (n = 344) drank ≥10 g of alcohol/d (4.9% >60 g of alcohol/d, 6.4% 10 to 60 g of alcohol/d, 88.7% <10 g of alcohol/d)). For the drinking limit of ≥10 g of alcohol/d, ROC curve analysis showed a balanced sensitivity and specificity, with an AUDIT-C cutoff of ≥4 for men (sensitivity: 70%, specificity: 83.6%; AUC = 0.823, CI = 0.718 to 0.928, p < 0.001) and ≥2 for women (sensitivity: 73.7%, specificity: 81.9%; AUC = 0.783, CI = 0.653 to 0.914, p < 0.001). Nursing staff (n = 274) underestimated alcohol consumption and evaluated 40% of the chronic-excessive alcohol consumers (>60 g of alcohol/d) as being abstinent. CONCLUSIONS: Our data suggest that an AUDIT-C cutoff of ≥4 for men and ≥2 for women can be recommended to detect the consumption of ≥10 g of alcohol/d in the elderly. Because the nursing staff to a large extent underestimates the alcohol consumption among nursing home residents, further teaching of the staff, improvement of screening instruments for the elderly, and the use of objective biomarkers might be helpful for recognizing hazardous drinking and can thus help improve the quality of life of the elderly.

Marketing Status and Perceived Efficacy of Drugs for Supporting Abstinence and Reducing Alcohol Intake in Alcohol Use Disorders: A Survey among European Federation of Addiction Societies in Europe.

BACKGROUND: Acamprosate, disulfiram (DIS), naltrexone and nalmefene can be used in treating alcohol use disorders. The drugs are, however, underutilized. METHODS: In this survey of marketing status and perceived efficacy, member societies of the European federation for addiction societies were asked to report on the status of these drugs in their country. Results were obtained from 20 European countries showing that the drugs were registered in most countries. RESULTS AND CONCLUSION: The drugs were mentioned in guidelines in approximately half and were partially or fully reimbursed in half to two-thirds countries. DIS was perceived as the most efficacious drug. These results are discussed.

Ethanol metabolites: their role in the assessment of alcohol intake.

BACKGROUND: Alcohol-related disorders are common, expensive in their course, and often underdiagnosed. To facilitate early diagnosis and therapy of alcohol-related disorders and to prevent later complications, questionnaires and biomarkers are useful. METHODS: Indirect state markers like gamma-glutamyl-transpeptidase, mean corpuscular volume, and carbohydrate deficient transferrin are influenced by age, gender, various substances, and nonalcohol-related illnesses, and do not cover the entire timeline for alcohol consumption. Ethanol (EtOH) metabolites, such as ethyl glucuronide, ethyl sulfate, phosphatidylethanol, and fatty acid ethyl esters have gained enormous interest in the last decades as they are detectable after EtOH intake. RESULTS: For each biomarker, pharmacological characteristics, detection methods in different body tissues, sensitivity/specificity values, cutoff values, time frames of detection, and general limitations are presented. Another focus of the review is the use of the markers in special clinical and forensic samples. CONCLUSIONS: Depending on the biological material used for analysis, ethanol metabolites can be applied in different settings such as assessment of alcohol intake, screening, prevention, diagnosis, and therapy of alcohol use disorders.

Cellular photo digital breathalyzer for monitoring alcohol use: a pilot study.

BACKGROUND: Monitoring alcohol use is important in numerous situations. Direct ethanol metabolites, such as ethyl glucuronide (EtG), have been shown to be useful tools in detecting alcohol use and documenting abstinence. For very frequent or continuous control of abstinence, they lack practicability. Therefore, devices measuring ethanol itself might be of interest. This pilot study aims at elucidating the usability and accuracy of the cellular photo digital breathalyzer (CPDB) compared to self-reports in a naturalistic setting. METHOD: 12 social drinkers were included. Subjects used a CPDB 4 times daily, kept diaries of alcohol use and submitted urine for EtG testing over a period of 5 weeks. RESULTS: In total, the 12 subjects reported 84 drinking episodes. 1,609 breath tests were performed and 55 urine EtG tests were collected. Of 84 drinking episodes, CPDB detected 98.8%. The compliance rate for breath testing was 96%. Of the 55 EtG tests submitted, 1 (1.8%) was positive. CONCLUSIONS: The data suggest that the CPDB device holds promise in detecting high, moderate, and low alcohol intake. It seems to have advantages compared to biomarkers and other monitoring devices. The preference for CPDB by the participants might explain the high compliance. Further studies including comparison with biomarkers and transdermal devices are needed.

Assessing the drinking status of liver transplant patients with alcoholic liver disease.

The accurate assessment of drinking by patients with alcoholic liver disease is important both before and after liver transplantation. Unfortunately, self-reports by these individuals often underestimate their actual alcohol consumption. Several recently developed biochemical measures can provide additional information on a patient's use of alcohol. This article describes ethyl glucuronide, ethyl sulfate, phosphatidyl ethanol, and carbohydrate-deficient transferrin as biomarkers of drinking and summarizes research dealing with their application in patients with alcohol use disorders who are candidates for or recipients of liver transplantation. The article also offers suggestions for enhancing the reliability of self-report measures of drinking status.

Phosphatidylethanol: the potential role in further evaluating low positive urinary ethyl glucuronide and ethyl sulfate results.

BACKGROUND: Whereas urinary ethyl glucuronide (EtG) levels above 1,000 ng/ml reflect with a high probability ethanol (EtOH) consumption, levels below this cutoff are difficult to interpret as both extraneous (nonbeverage) EtOH exposure, recent drinking, and more distant high EtOH intake (several days ago) might yield similar results. This might be of particular relevance in medico-legal cases. To overcome this dilemma, phosphatidylethanol (PEth) might be a promising marker, because blood PEth is only positive following significant alcohol use. The aim of our study was therefore to employ PEth as a marker to differentiate between the different conditions. METHODS: Subjects included were 252 participants in monitoring with the Alabama Physician Health Program. All subjects testing positive for EtG and/or ethyl sulfate (EtS) who denied drinking after routine supportive confrontation were subject to information about PEth testing. If they still denied drinking, PEth testing was performed and the result communicated. EtG, EtS, and PEth testing was performed in a commercial laboratory using liquid chromatography tandem mass spectrometry methods. RESULTS: Of a total of 18 subjects who tested positive for EtG and/or EtS, 10 denied drinking. Of the 7 who denied drinking after PEth explanation, in 5 cases, their claim was supported by a negative PEth result. In 2 cases, a positive PEth result was in contrast to their claim. CONCLUSIONS: PEth results in combination with previous low positive EtG/EtS results allow differentiating between innocent/extraneous exposure and drinking. Negative PEth testing following low positive EtG/EtS results helps to further elucidate the findings and support the claim of the patient of recent alcohol abstinence. Positive PEth testing following positive EtG/EtS results confirms recent drinking.

Characterization of sialic acid index of plasma apolipoprotein J and phosphatidylethanol during alcohol detoxification--a pilot study.

BACKGROUND: Apolipoprotein J (ApoJ) is a component of plasma high-density lipoproteins. Previous studies have shown progressive recovery of ApoJ sialic acid content with increased duration of alcohol abstinence. Therefore, the sialic acid index of plasma apolipoprotein J (SIJ) seems to be a promising alcohol biomarker. Phosphatidylethanol (PEth) is a direct ethanol metabolite and has recently attracted attention as a biomarker of prolonged intake of higher amounts of alcohol. The aim of the pilot study was to explore sensitivity, specificity, and normalization of SIJ and PEth in comparison with traditional and emerging biomarkers. METHODS: Five male alcohol-dependent patients (International Classification of Diseases 10, F 10.25) were included (median: 40 years old; Alcohol Use Disorders Identification Test value, 30; alcohol consumption in the previous 7 days, 1,680 g). SIJ, PEth, urinary ethyl glucuronide (UEtG), urinary ethyl sulfate (UEtS), and gamma glutamyl-transpeptidase (GGT) were determined at days 1, 3, 7, 10, 14, 21, and 28. RESULTS: At study entry, SIJ, PEth, UEtG, and UEtS were positive in all subjects, whereas GGT and mean corpuscular volume were positive in 3 of 5 (60%) of the subjects. Individual SIJ levels increased between day 1 and 28 between 13.7 and 44.3%, respectively. For SIJ and PEth, the ANOVA (p < 0.005) showed a significant trend with the average subject's SIJ and PEth changing 1.22 and 1.02, respectively, per week. CONCLUSIONS: Our preliminary data suggest that SIJ and PEth might hold potential as markers of heavy ethanol intake.

Phosphatidylethanol (PEth) as a biomarker of alcohol consumption in HIV-positive patients in sub-Saharan Africa.

BACKGROUND: Alcohol is heavily consumed in sub-Saharan Africa and affects HIV transmission and treatment and is difficult to measure. Our goal was to examine the test characteristics of a direct metabolite of alcohol consumption, phosphatidylethanol (PEth). METHODS: Persons infected with HIV were recruited from a large HIV clinic in southwestern Uganda. We conducted surveys and breath alcohol concentration (BRAC) testing at 21 daily home or drinking establishment visits, and blood was collected on day 21 (n = 77). PEth in whole blood was compared with prior 7-, 14-, and 21-day alcohol consumption. RESULTS: (i) The receiver operator characteristic area under the curve (ROC-AUC) was highest for PEth versus any consumption over the prior 21 days (0.92; 95% confidence interval [CI]: 0.86 to 0.97). The sensitivity for any detectable PEth was 88.0% (95% CI: 76.0 to 95.6) and the specificity was 88.5% (95% CI: 69.8 to 97.6). (ii) The ROC-AUC of PEth versus any 21-day alcohol consumption did not vary with age, body mass index, CD4 cell count, hepatitis B virus infection, and antiretroviral therapy status, but was higher for men compared with women (p = 0.03). (iii) PEth measurements were correlated with several measures of alcohol consumption, including number of drinking days in the prior 21 days (Spearman r = 0.74, p < 0.001) and BRAC (r = 0.75, p < 0.001). CONCLUSIONS: The data add support to the body of evidence for PEth as a useful marker of alcohol consumption with high ROC-AUC, sensitivity, and specificity. Future studies should further address the period and level of alcohol consumption for which PEth is detectable.

Association between leptin levels and doses of clomethiazole during alcohol withdrawal: a pilot study.

AIMS: The issue of leptin as a putative state marker of alcohol use and its role in craving has been raised in the last few years. Recently, a strong GABA-ergic modulation of leptin was postulated. The aim of the pilot study was to examine leptin levels in correlation with the strongly GABA-mimetic active substance clomethiazole. The main hypothesis was that higher doses of the strong GABA-mimetic clomethiazole are positively correlated with higher leptin levels. METHODS: Twenty-eight alcohol-dependent patients (3 females, median age 36 years) undergoing alcohol withdrawal were included. In 18 patients with and 10 without clomethiazole, serum leptin was analyzed at day 1 and day 7 of alcohol withdrawal. Both groups did not differ by age, BMI, or alcohol use characteristics. RESULTS: In the clomethiazole group, significant correlations were found between leptin levels at day 1 and clomethiazole dose (p = 0.004), clomethiazole and leptin at day 1/BMI (p = 0.009) and leptin at day 1 and clomethiazole/body surface (p = 0.006). Furthermore, patients with higher clomethiazole doses demonstrated significant higher leptin levels at day 1 (p = 0.044) and day 7 (p = 0.046). CONCLUSIONS: Our pilot data show a strong association between leptin levels and clomethiazole doses, thus supporting further research.

Association of ADH4 genetic variants with alcohol dependence risk and related phenotypes: results from a larger multicenter association study.

Genetic variants of the alcohol-metabolizing enzyme ADH4, located on chromosome 4q22-4q23, have been related to alcohol dependence (AD) risk in previous research. The aim of this association study in a large multicenter sample of alcohol-dependent individuals and controls is to confirm ADH4 single nucleotide polymorphism (SNP) and haplotype association with AD and relevant related phenotypes. One thousand, six hundred and twenty-two (1622) inpatient subjects and 1469 control subjects with DSM-IV. AD from four addiction treatment centres were included. Characteristics of AD and related phenotypes including alcohol withdrawal, Cloninger's type I and II and first ages of drinking, regular drinking and AD onset were obtained using standardized structured interviews. After subjects were genotyped for 2 ADH4 polymorphisms, single SNP case-control and haplotype analyses were conducted. Both variants--rs1800759 and rs1042364--and the A-A and C-G haplotypes were significantly related to AD across samples. Furthermore, associations with AD-related phenotypes and subtypes revealed a potential protective influence of this haplotype. This study confirms the significant relationship of ADH4 variants with AD and related phenotypes. While the rs1800759 and rs1042364 A-A haplotype had a potential protective influence on the risk for several AD-related phenotypes, this effect is rather small compared to functional variants of other alcohol or acetaldehyde-metabolizing enzymes like ALDH2*2 or ADH1B*2.

Chronic intake of fermented floral nectar by wild treeshrews.

For humans alcohol consumption often has devastating consequences. Wild mammals may also be behaviorally and physiologically challenged by alcohol in their food. Here, we provide a detailed account of chronic alcohol intake by mammals as part of a coevolved relationship with a plant. We discovered that seven mammalian species in a West Malaysian rainforest consume alcoholic nectar daily from flower buds of the bertam palm (Eugeissona tristis), which they pollinate. The 3.8% maximum alcohol concentration (mean: 0.6%; median: 0.5%) that we recorded is among the highest ever reported in a natural food. Nectar high in alcohol is facilitated by specialized flower buds that harbor a fermenting yeast community, including several species new to science. Pentailed treeshrews (Ptilocercus lowii) frequently consume alcohol doses from the inflorescences that would intoxicate humans. Yet, the flower-visiting mammals showed no signs of intoxication. Analysis of an alcohol metabolite (ethyl glucuronide) in their hair yielded concentrations higher than those in humans with similarly high alcohol intake. The pentailed treeshrew is considered a living model for extinct mammals representing the stock from which all extinct and living treeshrews and primates radiated. Therefore, we hypothesize that moderate to high alcohol intake was present early on in the evolution of these closely related lineages. It is yet unclear to what extent treeshrews benefit from ingested alcohol per se and how they mitigate the risk of continuous high blood alcohol concentrations.

Phosphatidylethanol for Monitoring Alcohol Use in Liver Transplant Candidates: An Observational Study.

Liver transplantation remains an essential procedure for many patients suffering from alcoholic liver disease. Alcohol use monitoring remains paramount all through the stages of this complex process. Direct alcohol biomarkers, with improved specificity and sensibility, should replace traditional indirect markers. Phosphatidylethanol (PEth) has been recently tested in alcoholic liver disease patients, but more evidence is needed, especially in comparison with other direct biomarkers. We conducted an observational study among patients awaiting liver transplantation. We analyzed Peth in blood, ethylglucuronide (EtG) in hair and urine and ethylsulphate (EtS) in urine, using mass spectrometry methods. In addition, transaminases, and self-reports were analyzed. A total of 50 patients were included (84% men, mean age 59 years (SD = 6)). 18 patients (36%) screened positive for any marker. Self-reports were positive in 3 patients. EtS was the biomarker with more positive screens. It also was the most frequently exclusive biomarker, screening positive in 7 patients who were negative for all other biomarkers. PEth was positive in 5 patients, being the only positive biomarker in 2 patients. It showed a false negative in a patient admitting alcohol use the previous week and screening positive for EtG and EtS. Hair EtG was positive in 3 patients who had negative Peth, EtG. EtG did not provide any exclusive positive result.A combination of biomarkers seems to be the best option to fully ascertain abstinence in this population. Our study suggest EtS might also play a significant role.

Deficient Decision Making in Pathological Gamblers Correlates With Gray Matter Volume in Medial Orbitofrontal Cortex.

Individuals suffering from pathological gambling (PG) show impaired decision making, but it is still not clear how this impairment is related to other traits and neuroanatomical characteristics. In this study, we investigated how the influence of PG on decision making (1) is connected to different impulsivity facets and (2) how it is related to gray matter volume (GMV) in various brain regions. Twenty-eight diagnosed PG patients and 23 healthy controls completed the cups task to measure decision making. In this task, participants had to decide between safe and risky options, which varied in expected value (EV) between risk advantageous, equal EV, and risk disadvantageous choices. A delay discounting task and the Barrant Impulsiveness Scale were applied to assess multiple impulsivity facets. In addition, structural magnetic resonance images were acquired. In comparison to the control group PG patients demonstrated more deficits in decision making, indicated by less EV sensitivity, but there was no significant difference in number of overall risky choices. Also, PG patients showed increased impulsivity in nearly every dimension. Results revealed (1) a positive correlation between decision making impairments and non-planning impulsivity but no significant relation to other impulsivity facets. Although we found no GMV differences between PG patients and controls, (2) a regions of interest analysis showed a correlation between medial orbitofrontal GMV and EV sensitivity in PG patients. Our findings showed that (1) the association between decision making and impulsivity can also be found in PG patients, but only for certain impulsivity facets. This suggests that it is essential to consider measuring different dimensions, when investigating impulsivity in a PG sample. Secondly, our findings revealed that (2) dysfunctional decision making-particularly the component of risk evaluation-is related to decreased GMV in the medial orbitofrontal cortex, a brain region concerned with processing of rewards. Interestingly, we did not find more risky choices for PG patients, and thus, we assume that decision making deficits in PG are primarily related to risk evaluation, not risk seeking, which is in line with our GMV findings.

Acute alcohol effects on impulsive choice in adolescents.

BACKGROUND: Neurodevelopmental and alcohol-induced changes in decision-making have been proposed to critically influence impulsive behaviour in adolescents. OBJECTIVE: This study tested the influence of acute alcohol administration on impulsive choice in adolescents. METHODS: Fifty-four males aged 18-19 years were tested in a single-blind placebo-controlled cross-over design. During alcohol administration (infusion resulting in an arterial blood alcohol concentration of 80 mg%) and placebo condition (saline infusion), participants performed a task battery providing estimates of delay discounting, probability discounting for gains, for losses and loss aversion, and also rated subjectively experienced alcohol effects. Additionally, baseline alcohol consumption (Alcohol Use Disorders Identification Test, blood phosphatidylethanol levels), motives (Drinking Motive Questionnaire, Alcohol Expectancy Questionnaire and Obsessive Compulsive Drinking Scale), family history and self-report measures of impulsivity (Barratt Impulsiveness Scale, Substance Use Risk Profile Scale) were provided. RESULTS: No overall effects of treatment on choice behaviour were found. However, individual differences were observed. In the alcohol condition, more impulsive choice tendencies for delay discounting were associated with higher subjectively experienced alcohol effects. Further, higher risk aversion for probabilistic gains and higher loss aversion during alcohol condition were related to higher levels of real-life alcohol consumption and a family history of alcohol problems, respectively. Finally, the time to make a decision was substantially shortened for choices involving negative prospects. CONCLUSIONS: Contrary to common beliefs, acute alcohol intoxication did not generally incite impulsive decision-making. It rather appears that alcohol-induced behavioural changes in adolescents vary considerably depending on prior experiences and subjective effects of alcohol.