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Translational Molecular Approaches in Substance Abuse Research.

ABSTRACT: Excessive abuse of psychoactive substances is one of the leading contributors to morbidity and mortality worldwide. In this book chapter, we review translational research strategies that are applied in the pursuit of new and more effective therapeutics for substance use disorder (SUD). The complex, multidimensional nature of psychiatric disorders like SUD presents difficult challenges to investigators. While animal models are critical for outlining the mechanistic relationships between defined behaviors and genetic and/or molecular changes, the heterogeneous pathophysiology of brain diseases is uniquely human, necessitating the use of human studies and translational research schemes. Translational research describes a cross-species approach in which findings from human patient-based data can be used to guide molecular genetic investigations in preclinical animal models in order to delineate the mechanisms of reward circuitry changes in the addicted state. Results from animal studies can then inform clinical investigations toward the development of novel treatments for SUD. Here we describe the strategies that are used to identify and functionally validate genetic variants in the human genome which may contribute to increased risk for SUD, starting from early candidate gene approaches to more recent genome-wide association studies. We will next examine studies aimed at understanding how transcriptional and epigenetic dysregulation in SUD can persistently alter cellular function in the disease state. In our discussion, we then focus on examples from the literature illustrating molecular genetic methodologies that have been applied to studies of different substances of abuse - from alcohol and nicotine to stimulants and opioids - in order to exemplify how these approaches can both delineate the underlying molecular systems driving drug addiction and provide insights into the genetic basis of SUD.

SUBMITTER: Fulton SL

PROVIDER: S-EPMC7166137 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Translational Molecular Approaches in Substance Abuse Research.

Fulton Sasha L SL Maze Ian I

Handbook of experimental pharmacology 20200101

Excessive abuse of psychoactive substances is one of the leading contributors to morbidity and mortality worldwide. In this book chapter, we review translational research strategies that are applied in the pursuit of new and more effective therapeutics for substance use disorder (SUD). The complex, multidimensional nature of psychiatric disorders like SUD presents difficult challenges to investigators. While animal models are critical for outlining the mechanistic relationships between defined b ...[more]

PMID: 31628598

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Project description:BackgroundWeb-based resources and social media platforms play an increasingly important role in health-related knowledge and experience sharing. There is a growing interest in the use of these novel data sources for epidemiological surveillance of substance use behaviors and trends.ObjectiveThe key aims were to describe the development and application of the drug abuse ontology (DAO) as a framework for analyzing web-based and social media data to inform public health and substance use research in the following areas: determining user knowledge, attitudes, and behaviors related to nonmedical use of buprenorphine and illicitly manufactured opioids through the analysis of web forum data Prescription Drug Abuse Online Surveillance; analyzing patterns and trends of cannabis product use in the context of evolving cannabis legalization policies in the United States through analysis of Twitter and web forum data (eDrugTrends); assessing trends in the availability of novel synthetic opioids through the analysis of cryptomarket data (eDarkTrends); and analyzing COVID-19 pandemic trends in social media data related to 13 states in the United States as per Mental Health America reports.MethodsThe domain and scope of the DAO were defined using competency questions from popular ontology methodology (101 ontology development). The 101 method includes determining the domain and scope of ontology, reusing existing knowledge, enumerating important terms in ontology, defining the classes, their properties and creating instances of the classes. The quality of the ontology was evaluated using a set of tools and best practices recognized by the semantic web community and the artificial intelligence community that engage in natural language processing.ResultsThe current version of the DAO comprises 315 classes, 31 relationships, and 814 instances among the classes. The ontology is flexible and can easily accommodate new concepts. The integration of the ontology with machine learning algorithms dramatically decreased the false alarm rate by adding external knowledge to the machine learning process. The ontology is recurrently updated to capture evolving concepts in different contexts and applied to analyze data related to social media and dark web marketplaces.ConclusionsThe DAO provides a powerful framework and a useful resource that can be expanded and adapted to a wide range of substance use and mental health domains to help advance big data analytics of web-based data for substance use epidemiology research.

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Translational Molecular Approaches in Substance Abuse Research.

Publications

Translational Molecular Approaches in Substance Abuse Research.

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