催产素和催产素基因受体甲基化在男性酒精使用障碍戒断治疗中的作用

IF 2.6 3区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Phileas J. Proskynitopoulos, Alissa F. Haarmeyer, Stefan Bleich, Helge Frieling, Thomas Hillemacher, Alexander Glahn, Mathias Rhein
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引用次数: 0

摘要

催产素是治疗酒精使用障碍(AUD)的一个有希望的治疗靶点。然而,许多研究报告了关于它对药物渴望、复发风险和戒断症状的影响的矛盾证据。催产素和催产素受体(OXTR)基因的表观遗传调控在一些精神障碍中发生改变,并影响社会行为,通常取决于潜在的性别。有证据表明,启动子甲基化的改变可能导致催产素和OXTR表达差异,从而可能影响药物渴望和复发风险。目前尚不清楚启动子甲基化是否在酒精戒断过程中发生变化,是否与渴望和戒断症状有关。在这项探索性研究中,我们调查了99名男性2周酒精戒断治疗对甲基化水平(催产素和OXTR)的影响,并与31名健康对照进行了比较。我们发现,在停药期间,对照组中OXTR基因的平均甲基化值明显高于患者(p < 0.001)。关于催产素,我们发现健康对照与患者的平均甲基化没有差异。在戒断期间,两种基因的平均甲基化水平均下降。拟合混合线性模型,渴望和戒断症状与催产素基因甲基化水平的变化相关(p < 0.001),当考虑年龄和吸烟作为附加协变量时,OXTR基因也是如此。我们的研究首次报道了AUD、催产素和OXTR基因甲基化之间的关联。与健康对照组相比,AUD患者的OXTR基因甲基化降低,而OT基因甲基化与渴望和戒断严重程度有关。我们的研究结果表明,研究催产素作为一种治疗药物需要考虑其受体和基因的表观遗传调控作为一种机制,可能影响催产素对渴望和戒断症状的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The Role of Oxytocin and Oxytocin Gene Receptor Methylation During Withdrawal Therapy in Males With Alcohol Use Disorder

The Role of Oxytocin and Oxytocin Gene Receptor Methylation During Withdrawal Therapy in Males With Alcohol Use Disorder

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.

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来源期刊
Addiction Biology
Addiction Biology 生物-生化与分子生物学
CiteScore
8.10
自引率
2.90%
发文量
118
审稿时长
6-12 weeks
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.
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