Understanding the relationship between pathological gambling and gambling-related cognition scores: the role of alcohol use disorder and delusion proneness

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.

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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.

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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.

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