Diagnosis and Pharmacotherapy of Alcohol Use Disorder

Kranzler, Henry R.; Soyka, Michael

doi:10.1001/jama.2018.11406

Cited by 477 publications

(423 citation statements)

References 69 publications

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“…Compulsive drinking, defined as the pathological motivation to consume alcohol, manifests as drinking despite negative consequences, such as job loss, legal problems, and damage to interpersonal relationships. This type of risky drinking is not addressed by currently approved AUD pharmacotherapies (2). The identification of the underlying brain mechanisms that promote compulsive drinking is critical for effective development of new interventions to treat AUD.…”

Section: Introductionmentioning

confidence: 99%

Perineuronal Nets in the Insula Regulate Aversion-Resistant Alcohol Drinking

Chen

Lasek

2018

Preprint

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One of the most pernicious characteristics of alcohol use disorder is the compulsion to drink despite negative consequences. The insular cortex (insula) controls decision-making under conditions of risk or conflict and regulates maladaptive behaviors in the context of addiction.Cortical activity is tightly controlled by fast-spiking inhibitory interneurons that are often enclosed by specialized extracellular matrix structures known as perineuronal nets, which regulate neuronal excitability and plasticity. Using a mouse model of compulsive drinking in which alcohol was adulterated with the bitter tastant quinine, we demonstrate that disrupting perineuronal nets in the insula rendered mice more sensitive to quinine-adulterated alcohol.Activation of the insula, as measured by c-fos expression, occurred during aversion-resistant drinking and was further enhanced by elimination of perineuronal nets. These results provide fundamental insight into neuroanatomical and cellular mechanisms that control compulsive drinking.

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Section: Introductionmentioning

confidence: 99%

Perineuronal Nets in the Insula Regulate Aversion-Resistant Alcohol Drinking

Chen

Lasek

2018

Preprint

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“…Among these, 437 SNPs in 61 genes had at least one heterozygote in either the AUD or control group (Supplementary Table 3). We adapted a high-throughput reporter assay, PASSPORT-seq [9], to identify 3'UTR variants that affect gene expression (RNA levels) in two neuroblastoma cell lines, SH-SY5Y and SK-N-BE (2). A schematic of the overall procedure is shown in Figure 2.…”

Section: Experimental Screening For Functional Snps In 3'utr Regionsmentioning

confidence: 99%

“…Alcohol use disorders (AUDs) are major public health problems [1][2][3]. Alcohol is a central nervous system depressant, and high levels of consumption over a long period may alter brain function to promote AUDs and damage the brain, in part by altering gene expression levels [4,5].…”

Section: Introductionmentioning

confidence: 99%

Allele-Specific Expression and High-Throughput Reporter Assay Reveal Functional Variants in Human Brains with Alcohol Use Disorders

Rao

et al. 2019

Preprint

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Transcriptome studies can identify genes whose expression differs between alcoholics and controls. To test which variants associated with alcohol use disorder (AUDs) may cause expression differences, we integrated deep RNA-seq and genome-wide association studies (GWAS) data from four postmortem brain regions of 30 AUDs subjects and 30 controls (social/non-drinkers) and analyzed allele-specific expression (ASE). We identified 90 genes with differential ASE in subjects with AUDs compared to controls. Of these, 61 genes contained 437 single nucleotide polymorphisms (SNPs) in the 3' untranslated regions (3'UTR) with at least one heterozygote among the subjects studied. Using a modified PASSPORT-seq (parallel assessment of polymorphisms in miRNA target-sites by sequencing) assay, we identified 25SNPs that showed affected RNA levels in a consistent manner in two neuroblastoma cell lines, SH-SY5Y and SK-N-BE(2). Many of these are in binding sites of miRNAs and RNA binding proteins, indicating that these SNPs are likely causal variants of AUD-associated differential ASE.

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“…Therefore, high-severity AUD patients should be engaged in abstention oriented treatment programs, starting by a detoxification treatment and following with relapse prevention treatment afterwards, with effective medications such as naltrexone, acamprosate or disulfiram, in addition to psycho-social treatment (Kranzler & Soyka, 2018).…”

Section: Science Publishing Groupmentioning

confidence: 99%

A clinical remission study of low-severity alcohol use disorder, treated with nalmefene

Guardia-Serecigni¹

2019

BIOMEDJ

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Background:When someone develops an alcohol use disorder (AUD), their addiction conditioning does not go away simply by refraining from drinking for some weeks or months. On the contrary, due to the deprivation effect, if one day they try to have just one alcoholic drink they will feel a strong and imperative biological necessity to keep drinking very fast, not being able to stop, which will lead to immediate negative consequences.The good news is that opiod receptor antagonists, such as naltrexone and nalmefene, have shown efficacy for reducing the deprivation effect, and for reducing alcohol consumption, in people who suffer from low-severity alcohol use disorders.

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Diagnosis and Pharmacotherapy of Alcohol Use Disorder

Cited by 477 publications

References 69 publications

Perineuronal Nets in the Insula Regulate Aversion-Resistant Alcohol Drinking

Perineuronal Nets in the Insula Regulate Aversion-Resistant Alcohol Drinking

Allele-Specific Expression and High-Throughput Reporter Assay Reveal Functional Variants in Human Brains with Alcohol Use Disorders

A clinical remission study of low-severity alcohol use disorder, treated with nalmefene

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