Phileas J. Proskynitopoulos, Alissa F. Haarmeyer, Stefan Bleich, Helge Frieling, Thomas Hillemacher, Alexander Glahn, Mathias Rhein
{"title":"The Role of Oxytocin and Oxytocin Gene Receptor Methylation During Withdrawal Therapy in Males With Alcohol Use Disorder","authors":"Phileas J. Proskynitopoulos, Alissa F. Haarmeyer, Stefan Bleich, Helge Frieling, Thomas Hillemacher, Alexander Glahn, Mathias Rhein","doi":"10.1111/adb.70060","DOIUrl":null,"url":null,"abstract":"<p>Oxytocin is a promising therapeutic target in the treatment of alcohol use disorder (AUD). However, many studies report contradicting evidence regarding its effect on drug craving, relapse risk and withdrawal symptoms. Epigenetic regulation of the oxytocin and oxytocin receptor (OXTR) gene is altered in several mental disorders and influences social behaviour, often depending on the underlying sex. Evidence suggests that altered promoter methylation could result in oxytocin and OXTR expression differences, thereby possibly influencing drug craving and relapse risk. It is unclear whether promoter methylation changes throughout alcohol withdrawal and is linked to craving and withdrawal symptoms. In this exploratory study, we investigated the effect of 2-week alcohol withdrawal therapy in 99 males on methylation levels (oxytocin and OXTR) compared with 31 healthy controls. We found significantly higher mean methylation values of the OXTR gene in controls than patients across withdrawal (<i>p</i> < 0.001). Regarding oxytocin, we found no differences in mean methylation in healthy controls compared with patients. Across withdrawal, mean methylation decreased in both genes. Fitting a mixed linear model, craving and withdrawal symptoms were associated with changes in methylation levels of the oxytocin gene (<i>p</i> < 0.001), which was also true for the OXTR gene when considering age and smoking as additional covariates. Our study is the first to report an association between AUD, oxytocin and OXTR gene methylation. Methylation of the OXTR gene is reduced in AUD compared with healthy controls, with OT gene methylation linked to craving and withdrawal severity. Our results suggest that investigations of oxytocin as a therapeutic agent need to consider epigenetic regulation of its receptor and gene as a mechanism that could influence oxytocin's effect on craving and withdrawal symptoms.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 7","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70060","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Addiction Biology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/adb.70060","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Oxytocin is a promising therapeutic target in the treatment of alcohol use disorder (AUD). However, many studies report contradicting evidence regarding its effect on drug craving, relapse risk and withdrawal symptoms. Epigenetic regulation of the oxytocin and oxytocin receptor (OXTR) gene is altered in several mental disorders and influences social behaviour, often depending on the underlying sex. Evidence suggests that altered promoter methylation could result in oxytocin and OXTR expression differences, thereby possibly influencing drug craving and relapse risk. It is unclear whether promoter methylation changes throughout alcohol withdrawal and is linked to craving and withdrawal symptoms. In this exploratory study, we investigated the effect of 2-week alcohol withdrawal therapy in 99 males on methylation levels (oxytocin and OXTR) compared with 31 healthy controls. We found significantly higher mean methylation values of the OXTR gene in controls than patients across withdrawal (p < 0.001). Regarding oxytocin, we found no differences in mean methylation in healthy controls compared with patients. Across withdrawal, mean methylation decreased in both genes. Fitting a mixed linear model, craving and withdrawal symptoms were associated with changes in methylation levels of the oxytocin gene (p < 0.001), which was also true for the OXTR gene when considering age and smoking as additional covariates. Our study is the first to report an association between AUD, oxytocin and OXTR gene methylation. Methylation of the OXTR gene is reduced in AUD compared with healthy controls, with OT gene methylation linked to craving and withdrawal severity. Our results suggest that investigations of oxytocin as a therapeutic agent need to consider epigenetic regulation of its receptor and gene as a mechanism that could influence oxytocin's effect on craving and withdrawal symptoms.
期刊介绍:
Addiction Biology is focused on neuroscience contributions and it aims to advance our understanding of the action of drugs of abuse and addictive processes. Papers are accepted in both animal experimentation or clinical research. The content is geared towards behavioral, molecular, genetic, biochemical, neuro-biological and pharmacology aspects of these fields.
Addiction Biology includes peer-reviewed original research reports and reviews.
Addiction Biology is published on behalf of the Society for the Study of Addiction to Alcohol and other Drugs (SSA). Members of the Society for the Study of Addiction receive the Journal as part of their annual membership subscription.