Genetics and pharmacogenetics of substance use disorders.
Ontology highlight
ABSTRACT:
SUBMITTER: Tao PL
PROVIDER: S-EPMC4176940 | biostudies-literature | 2013 Dec
REPOSITORIES: biostudies-literature
Publications
Genetics and pharmacogenetics of substance use disorders.
Tao Pao-Luh PL Chen Li-Shiun LS Chen Chih-Ken CK Liu Yu-Li YL
Journal of food and drug analysis 20131201 4
The "Genetics and Pharmacogenetics of Substance Use Disorder" session was chaired by Dr. Pao-Luh Tao and had three speakers. The speakers and their topics were: Dr. Li-Shiun Chen presented on Genomics and Personalized Medicine for Smoking Cessation Treatments, Dr. Chih-Ken Chen presented on the Genetics of Methamphetamine Abuse and Methamphetamine Psychosis, and Dr. Yu-Li Liu presented on a Pharmacogenomics Study in a Taiwan Methadone Maintenance Cohort. ...[more]
Similar Datasets
Project description:Substance use disorders (SUDs) are prevalent and result in an array of negative consequences. They are influenced by genetic factors (h2 = ~50%). Recent years have brought substantial progress in our understanding of the genetic etiology of SUDs and related traits. The present review covers the current state of the field for SUD genetics, including the epidemiology and genetic epidemiology of SUDs, findings from the first-generation of SUD genome-wide association studies (GWAS), cautions about translating GWAS findings to clinical settings, and suggested prioritizations for the next wave of SUD genetics efforts. Recent advances in SUD genetics have been facilitated by the assembly of large GWAS samples, and the development of state-of-the-art methods modeling the aggregate effect of genome-wide variation. These advances have confirmed that SUDs are highly polygenic with many variants across the genome conferring risk, the vast majority of which are of small effect. Downstream analyses have enabled finer resolution of the genetic architecture of SUDs and revealed insights into their genetic relationship with other psychiatric disorders. Recent efforts have also prioritized a closer examination of GWAS findings that have suggested non-uniform genetic influences across measures of substance use (e.g. consumption) and problematic use (e.g. SUD). Additional highlights from recent SUD GWAS include the robust confirmation of loci in alcohol metabolizing genes (e.g. ADH1B and ALDH2) affecting alcohol-related traits, and loci within the CHRNA5-CHRNA3-CHRNB4 gene cluster influencing nicotine-related traits. Similar successes are expected for cannabis, opioid, and cocaine use disorders as sample sizes approach those assembled for alcohol and nicotine.
| S-EPMC8477224 | biostudies-literature
Project description:Increased physician prescribing of opioids to treat chronic nonprogressive pain has been accompanied by an increase in opioid addiction. Twin studies of opioid addiction are consistent with an inherited component of risk, approximately 50%. Several genome-wide association study (GWAS) reports indicate that genetic risk for opioid addiction is conveyed by many alleles of small effect (odds ratios <1.5). These reports have detected alleles in potassium-ion-channel genes (KCNC1 and KCNG2) and in a glutamate receptor auxiliary protein (CNIH3). Additionally, a variant at the µ-opioid receptor gene (OPRM1), which regulates OPRM1 expression appears promising. In pharmacogenetics of opioid addictions, methadone dose may be regulated by variants in cytochrome P450 2B6 (CYP2B6), a methadone-metabolizing enzyme, and by a locus 300 kb 5' to OPRM1. A ?-opioid-receptor gene single-nucleotide polymorphism may predict treatment response to methadone versus buprenorphine. To achieve better progress, larger sample sizes are needed for GWAS research, including controls with chronic opioid exposure, but no addiction. Large clinical trials comparing effective pharmacotherapies for opioid addiction (naltrexone, methadone, and buprenorphine) are needed for pharmacogenetic progress.
| S-EPMC5741106 | biostudies-literature
Project description:Eating disorders (EDs) and substance use disorders (SUDs) frequently co-occur; however, the reasons for this are unclear. We review the current literature on genetic risk for EDs and SUDs, as well as preliminary findings exploring whether these classes of disorders have overlapping genetic risk. Overall, genetic factors contribute to individual differences in liability to multiple EDs and SUDs. Although initial family studies concluded that no shared familial (which includes genetic) risk between EDs and SUDs exists, twin studies suggest a moderate proportion of shared variance is attributable to overlapping genetic factors, particularly for those EDs characterized by binge eating and/or inappropriate compensatory behaviours. No adoption or molecular genetic studies have examined shared genetic risk between these classes of disorders. Research investigating binge eating and inappropriate compensatory behaviours using emerging statistical genetic methods, as well as examining gene-environment interplay, will provide important clues into the aetiology of comorbid EDs and SUDs.
| S-EPMC4738088 | biostudies-literature
Project description:This article reviews current advances in the genetics of substance use disorders (SUDs). Both genetic and environmental sources of risk are required to develop a complete picture of SUD etiology. Genetic sources of risk for SUDs are not highly substance specific in their effects. Genetic and environmental risks for SUDs typically do not only add together but also interact with each other over development. Risk gene identification for SUDs has been difficult, with one recent success in identifying nicotinic receptor variants that affect risk for nicotine dependence. The impact of genetic variants on SUD risk will individually be small. Although genetic epidemiologic methods are giving us an increasingly accurate map of broad causal pathways to SUDs, gene discovery will be needed to identify the specific biological systems. Identifying these risk genes and understanding their action will require large clinical samples, and interaction between these studies and work in model organisms.
| S-EPMC3297622 | biostudies-literature
Project description:Addictions are common psychiatric disorders that exert high cost to the individual and to society. Addictions are a result of the interplay of multiple genetic and environmental factors. They are characterized by phenotypic and genetic heterogeneity as well as polygenicity, implying a contribution of different neurobiological mechanisms to the clinical diagnosis. Therefore, treatments for most substance use disorders are often only partially effective, with a substantial proportion of patients failing to respond. To address heterogeneity and polygenicity, strategies have been developed to identify more homogeneous subgroups of patients and to characterize genes contributing to their phenotype. These include genetic linkage and association studies as well as functional genetic analysis using endophenotypes and animal behavioural experimentation. Applying these strategies in a translational context aims at improving therapeutic response by the identification of subgroups of addiction patients for individualized, targeted treatment strategies. This article aims to discuss strategies addressing heterogeneity and polygenicity of substance use disorders by presenting results of recent research on genetic and environmental components of addiction. It will also introduce the European IMAGEN study that aims to integrate methodical approaches discussed in order to identify the genetic and neurobiological basis of behavioural traits relevant to the development of addictions.
| S-EPMC2607332 | biostudies-literature
Project description:Addiction is a devastating disorder that produces persistent maladaptive changes to the central nervous system, including glial cells. Although there is an extensive body of literature examining the neuronal mechanisms of substance use disorders, effective therapies remain elusive. Glia, particularly microglia and astrocytes, have an emerging and meaningful role in a variety of processes beyond inflammation and immune surveillance, and may represent a promising therapeutic target. Indeed, glia actively modulate neurotransmission, synaptic connectivity and neural circuit function, and are critically poised to contribute to addictive-like brain states and behaviors. In this review, we argue that glia influence the cellular, molecular, and synaptic changes that occur in neurons following drug exposure, and that this cellular relationship is critically modified following drug exposure. We discuss direct actions of abused drugs on glial function through immune receptors, such as Toll-like receptor 4, as well as other mechanisms. We highlight how drugs of abuse affect glia-neural communication, and the profound effects that glial-derived factors have on neuronal excitability, structure, and function. Recent research demonstrates that glia have brain region-specific functions, and glia in different brain regions have distinct contributions to drug-associated behaviors. We will also evaluate the evidence demonstrating that glial activation is essential for drug reward and drug-induced dopamine release, and highlight clinical evidence showing that glial mechanisms contribute to drug abuse liability. In this review, we synthesize the extensive evidence that glia have a unique, pivotal, and underappreciated role in the development and maintenance of addiction.
| S-EPMC6428630 | biostudies-literature
Project description:BACKGROUND:Changes in the use of psychoactive substances and medications and in the occurrence of substance-related disorders enable assessment of the magni- tude of the anticipated negative consequences for the population. METHODS:Trends were analyzed in the consumption of tobacco, alcohol, cannabis and other illegal drugs, analgesics, and hypnotics/sedatives, as well as trends in substance-related disorders, as coded according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The data were derived from nine waves of the German Epidemiological Survey of Substance Abuse (Epidemiologischer Sucht- survey, ESA) from 1995 to 2018. The data were collected in written form or by means of a combination of paper and internet-based questionnaires or telephone interviews. RESULTS:The estimated prevalence rates of tobacco and alcohol consumption and the use of hypnotics/sedatives decreased over time. On the other hand, increasing prevalence rates were observed for the consumption of cannabis and other illegal drugs and the use of analgesics. The trends in substance-related disorders showed no statistically significant changes compared to the reference values for the year 2018, except for higher prevalence rates of nicotine dependence, alcohol abuse and dependence, analgesic dependence, and hypnotic/sedative dependence in the year 2012 only. CONCLUSION:Trends in tobacco and alcohol consumption imply a future decline in the burden to society from the morbidity, mortality, and economic costs related to these substances. An opposite development in cannabis use cannot be excluded. No increase over time was seen in the prevalence of analgesic dependence, but the observed increase in the use of analgesics demands critical attention.
| S-EPMC6804271 | biostudies-literature
Project description:In contrast to traditional pharmacodynamic approaches to treat substance-use disorders (SUDs), the use of biologics (vaccines, monoclonal antibodies, and genetically modified enzymes) is based on a pharmacokinetic principle: reduce the amount of (and, ideally, eliminate) abused drug entering the central nervous system (CNS). Preclinical studies indicate that biologics are effective in both facilitating abstinence and preventing relapse to abused substances ranging from nicotine to heroin. While data are still emerging, the results from multiple clinical trials can best be described as mixed. Nonetheless, these clinical studies have already provided important insights using 'first-generation' tools that may inform the development of effective and commercially viable biologics to treat tobacco-, cocaine-, and methamphetamine-use disorders.
| S-EPMC4593975 | biostudies-literature
Project description:While the majority of youth who experiment with alcohol and drugs do not develop problematic levels of use, 5% of adolescents and 15% of young adults meet criteria for a substance use disorder (SUD). Pharmacotherapy, in combination with behavioral interventions, has the potential to increase the likelihood of successful treatment for youth struggling with SUD; however, the literature in this area is limited. To date, there are no Food and Drug Administration (FDA)-approved medications for adolescent SUD, other than buprenorphine, which has been approved down to 16 years of age for opioid use disorder. Despite alcohol and cannabis being the most commonly used substances during adolescence, only three medications have been tested among this demographic, and only two have warranted further study (i.e., naltrexone for alcohol and N-acetylcysteine for cannabis use disorder). Although less common in adolescents and young adults, the most promising pharmacological findings for this age group are for opioid (buprenorphine) and tobacco (bupropion and varenicline) use disorders. In addition, despite the recent marked increases in electronic nicotine delivery systems (i.e., vaping) among youth, treatment strategies are still in their infancy and no recommendation exists for how to promote cessation for youth vaping. Current findings are limited by: small, demographically homogeneous samples; few trials, including a substantial number of youth younger than 18; low retention; medication adherence rates; and minimal information on effective dosing levels and long-term outcomes. Overall, pharmacotherapy may be a potentially effective strategy to increase treatment effects; however, more rigorous research trials are warranted before FDA approval would be granted for any of the potential adjunctive medications in this age group.
| S-EPMC6727439 | biostudies-literature
Project description:Substance use disorders represent a serious public health and social issue worldwide. Recent advances in our understanding of the neurobiological basis of the addictive processes have led to the development of a growing number of pharmacological agents to treat addictions. Despite this progress, there are no approved pharmacological treatments for cocaine, methamphetamine and cannabis addiction. Moving treatment development to the next stage will require novel ways of approaching substance use disorders. One such novel approach is to target individual vulnerabilities, such as cognitive function, sex differences and psychiatric comorbidities. This review provides a summary of promising pharmacotherapies for alcohol, opiate, stimulant and nicotine addictions. Many medications that target positive and negative reinforcement of drugs, as well as individual vulnerabilities to addiction, are in different phases of development. Clinical trials testing the efficacy of these medications for substance use disorder are warranted.
| S-EPMC4014020 | biostudies-literature