Dataset Information

Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis.

ABSTRACT: The genetic component of alcohol use disorder is substantial, but monozygotic twin discordance indicates a role for nonheritable differences that could be mediated by epigenetics. Despite growing evidence associating epigenetics and psychiatric disorders, it is unclear how epigenetics, particularly DNA methylation, relate to brain function and behavior, including drinking behavior.The authors carried out a genome-wide analysis of DNA methylation of 18 monozygotic twin pairs discordant for alcohol use disorder and validated differentially methylated regions. After validation, the authors characterized these differentially methylated regions using personality trait assessment and functional MRI in a sample of 499 adolescents.Hypermethylation in the 3'-protein-phosphatase-1G (PPM1G) gene locus was associated with alcohol use disorder. The authors found association of PPM1G hypermethylation with early escalation of alcohol use and increased impulsiveness. They also observed association of PPM1G hypermethylation with increased blood-oxygen-level-dependent response in the right subthalamic nucleus during an impulsiveness task.Overall, the authors provide first evidence for an epigenetic marker associated with alcohol consumption and its underlying neurobehavioral phenotype.

SUBMITTER: Ruggeri B

PROVIDER: S-EPMC4827248 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis.

Ruggeri Barbara B Nymberg Charlotte C Vuoksimaa Eero E Lourdusamy Anbarasu A Wong Cybele P CP Carvalho Fabiana M FM Jia Tianye T Cattrell Anna A Macare Christine C Banaschewski Tobias T Barker Gareth J GJ Bokde Arun L W AL Bromberg Uli U Büchel Christian C Conrod Patricia J PJ Fauth-Bühler Mira M Flor Herta H Frouin Vincent V Gallinat Jürgen J Garavan Hugh H Gowland Penny P Heinz Andreas A Ittermann Bernd B Martinot Jean-Luc JL Nees Frauke F Pausova Zdenka Z Paus Tomáš T Rietschel Marcella M Robbins Trevor T Smolka Michael N MN Spanagel Rainer R Bakalkin Georgy G Mill Jonathan J Sommer Wolfgang H WH Rose Richard J RJ Yan Jia J Aliev Fazil F Dick Danielle D Kaprio Jaakko J Desrivières Sylvane S Schumann Gunter G

The American journal of psychiatry 20150518 6

<h4>Objective</h4>The genetic component of alcohol use disorder is substantial, but monozygotic twin discordance indicates a role for nonheritable differences that could be mediated by epigenetics. Despite growing evidence associating epigenetics and psychiatric disorders, it is unclear how epigenetics, particularly DNA methylation, relate to brain function and behavior, including drinking behavior.<h4>Method</h4>The authors carried out a genome-wide analysis of DNA methylation of 18 monozygotic ...[more]

PMID: 25982659

Similar Datasets

Project description:RATIONALE:Compared to the general population, adult Attention-Deficit / Hyperactivity Disorder (ADHD) is more prevalent in patients with Alcohol Use Disorder (AUD). Impaired behavioral inhibition is a common characteristic in both ADHD and AUD. Relapse risk is increased in patients with AUD and comorbid, untreated ADHD and in AUD patients with increased neural cue-reactivity. OBJECTIVES:In this study, we examined the interaction between neural correlates of behavioral inhibition and alcohol cue-reactivity with a hybrid imaging task. METHODS:Out of 69 adult study participants, we included n?=?49 in our final analyses: Individuals had a diagnosis of either AUD (n?=?13), ADHD (n?=?14) or both (n?=?5), or were healthy controls (HC; n?=?17). The functional magnetic resonance imaging paradigm aimed to examine the combined effects of both an interference-inhibition task ("Simon-task") and an alcohol cue-reactivity task. Instead of segregating by diagnostic group, we pursued a dimensional approach in which we compared measures of AUD and ADHD severity, as well as the interaction of both, using multiple regression analyses. RESULTS:The four groups did not differ on the behavioral level on either the inhibition task or the alcohol cue-reactivity task. However, brain activation in frontal control and reward-related regions during completion of the combined tasks were related to ADHD and AUD severity (symptom load). During presentation of both alcohol cues and the inhibition task, participants with higher AUD and ADHD symptom load exhibited greater BOLD (blood oxygen level dependent) responses in subcortical reward-related regions. CONCLUSIONS:Our findings support the hypothesis that ADHD additionally diminishes inhibition ability in individuals with AUD. This may increase relapse risk when confronted with alcohol cues. Further, it is crucial for patients with comorbid AUD and ADHD to take into account not only reduced cognitive control over behavioral inhibition but also simultaneously heightened alcohol cue-reactivity.

Dataset Information

Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis.

Publications

Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets