Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder

Background: The efficacy of naltrexone in the treatment of alcohol use disorder (AUD) has been associated with a set of variables not directly related with the expression of opioid receptors. All the variables have been found to be highly associated with AUD itself or more severe clinical levels of AUD. Objectives: Given the high association between alcohol metabolizing enzymes (AME) and the outcome of AUD, the present study aims to investigate the role of AME genotype variants in the treatment of AUD with naltrexone. Methods: We carried out a 12-week longitudinal clinical trial based on the treatment of AUD patients with naltrexone (N = 101), stratified by different alcohol metabolization genotypes. Genotyping was performed after the inclusion of the patients in the study, based on the individual presence of single nucleotide polymorphisms (SNPs) in the ADH (alcohol dehydrogenase)1B (ADH1B*2 and ADH1B*3), ADH1C (ADHC*1) and ALDH (aldehyde dehydrogenase) 2 (ALDH2*2) genes. The outcome of alcohol use has been monitored employing the timeline follow-back during the treatment. Results: The ADH1C*1 (Ile350Val, rs698) and ALDH2*2 (Glu504Lys, rs671) polymorphisms were associated with a better response to naltrexone treatment, whereas the ADH1B*3 (Arg370Cys, rs2066702) allelic variant showed a negative outcome. Conclusions: The present study explores a genomic setting for the treatment of AUD with naltrexone. According to our findings, the association between ADH1C*1 and ALDH2*2 variants and better outcomes suggests a successful treatment, whereas the ADH1B*3 mutated allele might lead to an unsuccessful treatment. Further studies should be performed to investigate the relationship between alcohol metabolizing genotypes, the family history of alcohol use disorders and the effect of naltrexone on the outcomes. Genotyping may be a valuable tool for precision-medicine and individualized approach, especially in the context of alcohol use disorders. The small number of subjects was the main limitation of the present study.

Download Full-text

mTORC and PKCε in Regulation of Alcohol Use Disorder

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200624122325 ◽

2020 ◽

Vol 20 (17) ◽

pp. 1696-1708 ◽

Cited By ~ 1

Author(s):

Athirah Hanim ◽

Isa Naina Mohamed ◽

Rashidi M. Pakri Mohamed ◽

Srijit Das ◽

Norefrina Shafinaz Md Nor ◽

...

Keyword(s):

Alcohol Use ◽

Alcohol Use Disorder ◽

Alcohol Intake ◽

Potential Role ◽

Synaptic Proteins ◽

Cellular Mechanisms ◽

Kinase C ◽

Protein Kinase C Epsilon ◽

Seeking Behavior

Alcohol use disorder (AUD) is characterized by compulsive binge alcohol intake, leading to various health and social harms. Protein Kinase C epsilon (PKCε), a specific family of PKC isoenzyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinases like the mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCε or vice versa in AUD. mTORC2 phosphorylates PKCε at hydrophobic and turn motif, and was recently reported to be associated with alcohol-seeking behavior, suggesting the potential role of mTORC2-PKCε interactions in the pathophysiology of AUD. mTORC1 regulates translation of synaptic proteins involved in alcohol-induced plasticity. Hence, in this article, we aimed to review the molecular composition of mTORC1 and mTORC2, drugs targeting PKCε, mTORC1, and mTORC2 in AUD, upstream regulation of mTORC1 and mTORC2 in AUD and downstream cellular mechanisms of mTORCs in the pathogenesis of AUD.

Download Full-text

Personality Processes Related to the Development and Resolution of Alcohol Use Disorders

10.1093/oso/9780190676001.003.0017 ◽

2018 ◽

Author(s):

Kenneth J. Sher ◽

Andrew Littlefield ◽

Matthew Lee

Keyword(s):

Alcohol Use ◽

Personality Traits ◽

Alcohol Use Disorder ◽

Alcohol Use Disorders ◽

Past Research ◽

Life Transitions ◽

Is Research ◽

Personality Research ◽

Adult Role ◽

Static View

This chapter discusses relations between personality and alcohol use disorder (AUD). After reviewing basic terms and concepts in personality research, two major areas of contemporary research are discussed. The first area concerns how personality traits are implicated in etiologic pathways to AUD. This highlights the centrality of personality to conceptualizing AUD and related psychopathology. The second area is research emphasizing movement beyond a static view of personality, recognizing that personality traits are dynamic and change as a function of human development and life transitions. In particular, whereas past research on “maturing out” of AUD emphasized salutary effects of young adult role transitions, recent evidence reveals normative patterns of developmental personality maturation and supports these as additional influences on maturing out. The chapter discusses ways that contextual role effects and personality maturation can perhaps be integrated into a broader model of maturing out of AUD. Implications for future investigation are presented.

Download Full-text

Alcohol Use Disorder

10.1093/oso/9780190676001.003.0005 ◽

2018 ◽

Author(s):

Igor Ponomarev

Keyword(s):

Alcohol Use ◽

Alcohol Use Disorder ◽

Critical Discussion ◽

Epigenetic Mechanisms ◽

Future Directions ◽

Clinically Significant ◽

Early Life Exposures ◽

The Brain ◽

Epigenetic Research

Alcohol use disorder (AUD) is characterized by clinically significant impairments in health and social function. Epigenetic mechanisms of gene regulation may provide an attractive explanation for how early life exposures to alcohol contribute to the development of AUD and exert lifelong effects on the brain. This chapter provides a critical discussion of the role of epigenetic mechanisms in AUD etiology and the potential of epigenetic research to improve diagnosis, evaluate risks for alcohol-induced pathologies, and promote development of novel therapies for the prevention and treatment of AUD. Challenges of the current epigenetic approaches and future directions are also discussed.

Download Full-text

A Developmental Perspective on the Genetic Basis of Alcohol Use Disorder

10.1093/oso/9780190676001.003.0004 ◽

2018 ◽

Author(s):

Elisa M. Trucco ◽

Gabriel L. Schlomer ◽

Brian M. Hicks

Keyword(s):

Alcohol Use ◽

Alcohol Use Disorder ◽

Developmental Perspective ◽

Relative Contribution ◽

Intermediate Phenotypes ◽

Problematic Alcohol ◽

Age Related ◽

Genetic And Environmental Factors ◽

Problematic Alcohol Use

Approximately 48–66% of the variation in alcohol use disorders is heritable. This chapter provides an overview of the genetic influences that contribute to alcohol use disorder within a developmental perspective. Namely, risk for problematic alcohol use is framed as a function of age-related changes in the relative contribution of genetic and environmental factors and an end state of developmental processes. This chapter discusses the role of development in the association between genes and the environment on risk for alcohol use disorder. Designs used to identify genetic factors relevant to problematic alcohol use are discussed. Studies examining developmental pathways to alcohol use disorder with a focus on endophenotypes and intermediate phenotypes are reviewed. Finally, areas for further investigation are offered.

Download Full-text

Implications of Heterogeneity in Alcohol Use Disorders for Understanding Developmental Pathways and Prevention Programming

10.1093/oso/9780190676001.003.0003 ◽

2018 ◽

Cited By ~ 1

Author(s):

Andrea M. Hussong ◽

W. Andrew Rothenberg ◽

Ruth K Smith ◽

Maleeha Haroon

Keyword(s):

Alcohol Use ◽

Alcohol Use Disorder ◽

Behavioral Control ◽

Alcohol Use Disorders ◽

Developmental Pathways ◽

Prevention Programming ◽

Preventive Program ◽

Innovative Methods ◽

Core Deficit ◽

Internalizing And Externalizing

This chapter discusses current conceptualizations of heterogeneity in alcohol use disorder (AUD), characterizes developmental pathways that lead to different subtypes of AUDs, and discusses how such pathways can inform preventive program design. Specifically, it reviews the “internalizing” and “externalizing” developmental pathways to AUDs. The externalizing pathway is characterized by a core deficit in behavioral control, whereas the internalizing pathway is characterized by a core deficit in emotion regulation. Both pathways predict drinking onset and escalation to AUD for some individuals. The chapter calls for the development of interventions to treat early childhood precursors to AUDs, innovative methods to identify individuals at risk for early emerging AUDs, additional investigation of how core pathway deficits operate across development, and greater consideration of how externalizing and internalizing pathways may interact within and across individuals.

Download Full-text

The role of pubertal timing in the link between family history of alcohol use disorder and late adolescent substance use

Drug and Alcohol Dependence ◽

10.1016/j.drugalcdep.2020.107955 ◽

2020 ◽

Vol 210 ◽

pp. 107955

Author(s):

Alexander S. Weigard ◽

Jillian E. Hardee ◽

Robert A. Zucker ◽

Mary M. Heitzeg ◽

Adriene M. Beltz

Keyword(s):

Substance Use ◽

Family History ◽

Alcohol Use ◽

Alcohol Use Disorder ◽

Pubertal Timing ◽

Adolescent Substance Use ◽

Late Adolescent ◽

Adolescent Substance ◽

History Of

Download Full-text

Assessment of alcohol use disorder and its associated factors among alcohol users of medical and surgical outpatients attending a specialized hospital in Gondar, Ethiopia: a cross-sectional study

International Journal of Mental Health Systems ◽

10.1186/s13033-021-00454-2 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Demeke Demilew ◽

Berhanu Boru ◽

Getachew Tesfaw ◽

Habtamu Kerebih ◽

Endalamaw Salelew

Keyword(s):

Alcohol Use ◽

Associated Factors ◽

Alcohol Use Disorder ◽

Alcohol Use Disorders ◽

Cross Sectional Study ◽

Sectional Study ◽

Multivariate Logistic Regression ◽

Cross Sectional ◽

History Of ◽

Male Sex

Abstract Background Alcohol use disorder increase the risk of physical harm, mental or social consequences for patients and others in the community. Studies on alcohol use disorder and associated factors among medical and surgical outpatients in Ethiopia are limited. Therefore, this study is meant to provide essential data on alcohol use disorder and associated factors among alcohol user medical and surgical outpatients to intervene in the future. Methods An institution-based cross-sectional study was conducted by using the systematic random sampling technique. Alcohol use disorders were assessed using the World Health Organization’s 10-item Alcohol Use Disorder Identification Test (AUDIT) questionnaire. Bivariate and multivariate logistic regression analyses were performed, a P-value less than 0.05 were considered statistically significant in the multivariate analysis and the strength of association was measured at a 95% confidence interval. Results The prevalence of alcohol use disorder was 34.5% with a 95% CI (29.20, 39.80) among study participants. In the multivariate logistic regression analysis, male sex (AOR = 3.33, 95%CI: 1.40, 7.93), history of mental illness (AOR = 2.68, 95%CI: 1.12, 6.38), drinking for relaxation (AOR = 1.88, 95%CI: 1.02, 3.48) and history of lifetime tobacco use (AOR = 5.64, 95%CI: 1.95, 16.29) were factors significantly associated with alcohol use disorder. Conclusion The prevalence of alcohol use disorders among medical and surgical outpatients was found to be high. Male sex, history of mental illness, alcohol use for relaxation and lifetime cigarette smoking need more attention during the assessment of patients in the medical and surgical outpatient departments.

Download Full-text

Emotional difficulties among individuals with alcohol use disorder: the mediating role of psychological mechanisms linked to mindfulness

Journal of Substance Use ◽

10.1080/14659891.2020.1745310 ◽

2020 ◽

Vol 25 (5) ◽

pp. 561-568

Author(s):

Marco Cavicchioli ◽

Pietro Ramella ◽

Giulia Simone ◽

Giulia Vassena ◽

Mariagrazia Movalli ◽

...

Keyword(s):

Alcohol Use ◽

Alcohol Use Disorder ◽

Emotional Difficulties ◽

Mediating Role ◽

Psychological Mechanisms

Download Full-text

An observational study to determine the prevalence of alcohol use disorders in advanced cancer patients

Palliative Medicine ◽

10.1177/0269216311409474 ◽

2011 ◽

Vol 26 (4) ◽

pp. 360-367 ◽

Cited By ~ 5

Author(s):

Katherine Webber ◽

Andrew N Davies

Keyword(s):

Alcohol Use ◽

Cancer Patients ◽

Advanced Cancer ◽

Alcohol Use Disorder ◽

Smoking Status ◽

Alcohol Use Disorders ◽

Symptom Burden ◽

Advanced Cancer Patients ◽

Current Smoking Status ◽

Current Smoking

Context: observational studies in North America suggest alcohol dependence is a common problem in advanced cancer patients and is associated with a high burden of physical and psychological symptoms. The prevalence of all types of alcohol use disorders, and the relationship between alcohol use disorders and symptoms, has not been studied. Objectives: this observational, cross-sectional study was designed to determine the prevalence of alcohol use disorders in patients with advanced cancer and establish if such patients have a higher symptom burden. Methods: sequential patients referred to the palliative medicine team at a United Kingdom cancer centre completed the Alcohol Use Disorders Identification Test, Hospital Anxiety and Depression Scale (HADS) and Memorial Symptom Assessment Scale-Short Form (MSAS-SF). Results: 120 patients participated in the study. Twenty-two (18%) patients screened positively for the presence of an alcohol use disorder. This study found no significant association between alcohol use disorders and the presence of anxiety ( P = 0.38) or depression ( P = 0.81) on the HADS or the global distress index subscale ( P = 0.142), physical symptom distress index subscale ( P = 0.734), or the psychological distress index subscale ( P = 0.154) on the MSAS-SF. Current smoking status was the only independent predictor for the presence of an alcohol use disorder ( P < 0.001). Seven (6%) patients screened positively for high-risk alcohol use disorders. Current smoking status ( P < 0.001) and male gender ( p < 0.001) were independent predictors of this problem. Conclusions: alcohol use disorders in this cohort of patients were not associated with a higher symptom burden, and the prevalence was lower than the general United Kingdom population.

Download Full-text