Resistance to Temptation: The Interaction of External and Internal Control on Alcohol Use During Residential Treatment for Alcohol Use Disorder

Background: There is evidence that drinking during residential treatment is related to various factors, such as patients’ general control beliefs and self-efficacy, as well as to external control of alcohol use by program’s staff and situations where there is temptation to drink. As alcohol use during treatment has been shown to be associated with the resumption of alcohol use after discharge from residential treatment, we aimed to investigate how these variables are related to alcohol use during abstinenceoriented residential treatment programs for alcohol use disorders (AUD). Methods: In total, 509 patients who entered 1 of 2 residential abstinence-oriented treatment programs for AUD were included in the study. After detoxification, patients completed a standardized diagnostic procedure including interviews and questionnaires. Drinking was assessed by patients’ selfreport of at least 1 standard drink or by positive breathalyzer testing. The 2 residential programs were categorized as high or low control according to the average number of tests per patient. Results: Regression analysis revealed a significant interaction effect between internal and external control suggesting that patients with high internal locus of control and high frequency of control by staff demonstrated the least alcohol use during treatment (16.7%) while patients with low internal locus of control in programs with low external control were more likely to use alcohol during Treatment (45.9%). No effects were found for self-efficacy and temptation. Conclusions: As alcohol use during treatment is most likely associated with poor treatment outcomes, external control may improve treatment outcomes and particularly support patients with low internal locus of control, who show the highest risk for alcohol use during treatment. High external control may complement high internal control to improve alcohol use prevention while in treatment. Key Words: Alcohol Dependence, Alcohol Use, Locus of Control, Alcohol Testing.

Brain activation during craving for alcohol measured by positron emission tomography

OBJECTIVE: Craving for alcohol is probably involved in acquisition and maintenance of alcohol dependence to a substantial degree. However, the brain substrates and mechanisms that underlie alcohol craving await more detailed elucidation. METHOD: Positron emission tomography was used to map regional cerebral blood flow (CBF) in 21 detoxified patients with alcohol dependence during exposure to alcoholic and non-alcoholic beverages. RESULTS: During the alcohol condition compared with the control condition, significantly increased CBF was found in the ventral putamen. Additionally, activated areas included insula, dorsolateral prefrontal cortex and cerebellum. Cerebral blood flow increase in these regions was related to self-reports of craving assessed in the alcoholic patients. CONCLUSIONS: In this investigation, cue-induced alcohol craving was associated with activation of brain regions particularly involved in brain reward mechanisms, memory and attentional processes. These results are consistent with studies on craving for other addictive substances and may offer strategies for more elaborate studies on the neurobiology of addiction.

Alcohol and colorectal cancer: the role of alcohol dehydrogenase 1C polymorphism

BACKGROUND: Chronic alcohol consumption is a risk factor for colorectal cancer. Animal experiments as well as genetic linkage studies in Japanese individuals with inactive acetaldehyde dehydrogenase leading to elevated acetaldehyde concentrations following ethanol ingestion support the hypothesis that acetaldehyde may be responsible for this carcinogenic effect of alcohol. In Caucasians, a polymorphism of alcohol dehydrogenase 1C (ADH1C) exists resulting in different acetaldehyde concentrations following ethanol oxidation. METHODS: To evaluate whether the association between alcohol consumption and colorectal tumor development is modified by ADH1C polymorphism, we recruited 173 individuals with colorectal tumors diagnosed by colonoscopy and 788 control individuals without colorectal tumors. Genotyping was performed using genomic DNA extracted from whole blood followed by polymerase chain reaction. RESULTS: Genotype ADH1C*1/1 was more frequent in patients with alcohol-associated colorectal neoplasia compared to patients without cancers in the multivariate model controlling for age, gender, and alcohol intake (odds ratio = 1.674, 95% confidence interval = 1.110-2.524, 2-sided p from Wald test = 0.0139). In addition, the joint test of the genetic effect and interaction between ADH1C genotype and alcohol intake (2-sided p = 0.0007) indicated that the difference in ADH1C*1 polymorphisms between controls and colorectal neoplasia is strongly influenced by the alcohol consumption and that only individuals drinking more than 30 g ethanol per day with the genotype ADH1C*1/1 had an increased risk for colorectal tumors. CONCLUSIONS: These data identify ADH1C homozygosity as a genetic risk marker for colorectal tumors in individuals consuming more than 30 g alcohol per day and emphasize the role of acetaldehyde as a carcinogenic agent in alcohol-related colorectal carcinogenesis.

Hepatitis C virus drug resistance and immune-driven adaptations: relevance to new antiviral therapy

The efficacy of specifically targeted anti-viral therapy for hepatitis C virus (HCV) (STAT-C), including HCV protease and polymerase inhibitors, is limited by the presence of drug-specific viral resistance mutations within the targeted proteins. Genetic diversity within these viral proteins also evolves under selective pressures provided by host human leukocyte antigen (HLA)-restricted immune responses, which may therefore influence STAT-C treatment response. Here, the prevalence of drug resistance mutations relevant to 27 developmental STAT-C drugs, and the potential for drug and immune selective pressures to intersect at sites along the HCV genome, is explored. HCV nonstructural (NS) 3 protease or NS5B polymerase sequences and HLA assignment were obtained from study populations from Australia, Switzerland, and the United Kingdom. Four hundred five treatment-naïve individuals with chronic HCV infection were considered (259 genotype 1, 146 genotype 3), of which 38.5% were coinfected with human immunodeficiency virus (HIV). We identified preexisting STAT-C drug resistance mutations in sequences from this large cohort. The frequency of the variations varied according to individual STAT-C drug and HCV genotype/subtype. Of individuals infected with subtype 1a, 21.5% exhibited genetic variation at a known drug resistance site. Furthermore, we identified areas in HCV protease and polymerase that are under both potential HLA-driven pressure and therapy selection and identified six HLA-associated polymorphisms (P drug resistance sites. CONCLUSION: Drug and host immune responses are likely to provide powerful selection forces that shape HCV genetic diversity and replication dynamics. Consideration of HCV viral adaptation in terms of drug resistance as well as host "immune resistance" in the STAT-C treatment era could provide important information toward an optimized and individualized therapy for chronic hepatitis C.

Progress in Monitoring alcohol consumption and alcohhol abuse by phosphatidylethanol

For early diagnosis and therapy of alcohol-related disorders, alcohol biomarkers are highly valuable. Concerning specificity, indirect markers can be influenced by nonethanol-related factors, whereas direct markers are only formed after ethanol consumption. Sensitivity of the direct markers depends on cutoffs of analytical methods, material for analysis and plays an important role for their utilization in different fields of application. Until recently, the biomarker phosphatidylethanol has been used to differentiate between social drinking and alcohol abuse. After method optimization, the detection limit could be lowered and phosphatidylethanol became sensitive enough to even detect the consumption of low amounts of alcohol. This perspective gives a summary of most common alcohol biomarkers and summarizes new developments for monitoring alcohol consumption habits.

Linking altered central pain processing and genetic polymorphism to drug efficacy in chronic low back pain.

BACKGROUND Inability to predict the therapeutic effect of a drug in individual pain patients prolongs the process of drug and dose finding until satisfactory pharmacotherapy can be achieved. Many chronic pain conditions are associated with hypersensitivity of the nervous system or impaired endogenous pain modulation. Pharmacotherapy often aims at influencing these disturbed nociceptive processes. Its effect might therefore depend on the extent to which they are altered. Quantitative sensory testing (QST) can evaluate various aspects of pain processing and might therefore be able to predict the analgesic efficacy of a given drug. In the present study three drugs commonly used in the pharmacological management of chronic low back pain are investigated. The primary objective is to examine the ability of QST to predict pain reduction. As a secondary objective, the analgesic effects of these drugs and their effect on QST are evaluated. METHODS/DESIGN In this randomized, double blinded, placebo controlled cross-over study, patients with chronic low back pain are randomly assigned to imipramine, oxycodone or clobazam versus active placebo. QST is assessed at baseline, 1 and 2 h after drug administration. Pain intensity, side effects and patients' global impression of change are assessed in intervals of 30 min up to two hours after drug intake. Baseline QST is used as explanatory variable to predict drug effect. The change in QST over time is analyzed to describe the pharmacodynamic effects of each drug on experimental pain modalities. Genetic polymorphisms are analyzed as co-variables. DISCUSSION Pharmacotherapy is a mainstay in chronic pain treatment. Antidepressants, anticonvulsants and opioids are frequently prescribed in a "trial and error" fashion, without knowledge however, which drug suits best which patient. The present study addresses the important need to translate recent advances in pain research to clinical practice. Assessing the predictive value of central hypersensitivity and endogenous pain modulation could allow for the implementation of a mechanism-based treatment strategy in individual patients. TRIAL REGISTRATION Clinicaltrials.gov, NCT01179828.