Methylation of the Oxytocin, Oxytocin Receptor, and Vasopressin Gene Promoters in Tobacco Use Disorder during Cessation.

IF 2.3 4区心理学 Q3 NEUROSCIENCES

Neuropsychobiology Pub Date : 2024-01-01 Epub Date: 2024-01-05 DOI:10.1159/000535663

Phileas Johannes Proskynitopoulos, Stefan Bleich, Marc Andre Nicolas Muschler, Vanessa Buchholz, Helge Frieling, Alexander Glahn, Mathias Rhein

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引用次数: 0

Abstract

Introduction: Vasopressin (AVP) and oxytocin (OT) exert sex-specific effects on social pair bonding and stress reactions while also influencing craving in substance use disorders. In this regard, intranasal oxytocin (OT) and AVP antagonists present potential treatments for tobacco use disorder (TUD). Since transcription of both hormones is also regulated by gene methylation, we hypothesized sex-specific changes in methylation levels of the AVP, OT, and OT receptor (OXTR) gene during nicotine withdrawal.

Methods: The study population consisted of 49 smokers (29 males, 20 females) and 51 healthy non-smokers (25 males, 26 females). Blood was drawn at day 1, day 7, and day 14 of smoking cessation. Craving was assessed with the questionnaire on smoking urges (QSU).

Results: Throughout cessation, mean methylation of the OT promoter gene increased in males and decreased in females. OXTR receptor methylation decreased in females, while in males it was significantly lower at day 7. Regarding the AVP promoter, mean methylation increased in males while there were no changes in females. Using mixed linear modeling, CpG position, time point, sex, and the interaction of time point and sex as well as time point, sex, and QSU had a significant fixed effect on OT and AVP gene methylation. The interaction effect suggests that sex, time point, and QSU are interrelated, meaning that, depending on the sex, methylation could be different at different time points and vice versa. There was no significant effect of QSU on mean OXTR methylation.

Discussion: We identified differences at specific CpGs between controls and smokers in OT and AVP and in overall methylation of the AVP gene. Furthermore, we found sex-specific changes in mean methylation levels of the mentioned genes throughout smoking cessation, underlining the relevance of sex in the OT and vasopressin system. This is the first study on epigenetic regulation of the OT promoter in TUD. Our results have implications for research on the utility of the AVP and OT system for treating substance craving. Future studies on both targets need to analyze their effect in the context of sex, social factors, and gene regulation.

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戒烟过程中催产素、催产素受体和血管加压素基因启动子的甲基化。

简介：血管加压素（AVP）和催产素（OT）对社会配对结合和应激反应具有性别特异性影响，同时也影响药物使用障碍患者的渴求。因此，鼻内催产素（OT）和 AVP 拮抗剂是治疗烟草使用障碍（TUD）的潜在疗法。由于这两种激素的转录也受基因甲基化的调控，我们假设在尼古丁戒断期间，AVP、OT和OT受体（OXTR）基因的甲基化水平会发生性别特异性变化：研究对象包括 49 名吸烟者（29 名男性，20 名女性）和 51 名健康非吸烟者（25 名男性，26 名女性）。分别在戒烟第 1 天、第 7 天和第 14 天抽血。结果显示，在整个戒烟过程中，甲基化的平均值都在下降：结果：在整个戒烟过程中，男性 OT 启动子基因的平均甲基化程度升高，而女性则降低。女性的 OXTR 受体甲基化程度降低，而男性在第 7 天显著降低。至于 AVP 启动子，男性的平均甲基化程度升高，而女性则没有变化。通过混合线性建模，CpG位置、时间点、性别、时间点与性别的交互作用以及时间点、性别和QSU对OT和AVP基因甲基化有显著的固定影响。交互作用效应表明，性别、时间点和 QSU 是相互关联的，也就是说，根据性别的不同，甲基化在不同的时间点可能不同，反之亦然。QSU对OXTR平均甲基化没有明显影响：讨论：我们发现对照组和吸烟者在 OT 和 AVP 的特定 CpGs 以及 AVP 基因的整体甲基化方面存在差异。此外，我们还发现在整个戒烟过程中，上述基因的平均甲基化水平存在性别特异性变化，这凸显了性别在 OT 和血管加压素系统中的相关性。这是首次对TUD中OT启动子的表观遗传调控进行研究。我们的研究结果对研究 AVP 和 OT 系统治疗药物渴求的效用具有重要意义。未来对这两个靶点的研究需要结合性别、社会因素和基因调控来分析它们的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropsychobiology 医学-精神病学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： The biological approach to mental disorders continues to yield innovative findings of clinical importance, particularly if methodologies are combined. This journal collects high quality empirical studies from various experimental and clinical approaches in the fields of Biological Psychiatry, Biological Psychology and Neuropsychology. It features original, clinical and basic research in the fields of neurophysiology and functional imaging, neuropharmacology and neurochemistry, neuroendocrinology and neuroimmunology, genetics and their relationships with normal psychology and psychopathology. In addition, the reader will find studies on animal models of mental disorders and therapeutic interventions, and pharmacoelectroencephalographic studies. Regular reviews report new methodologic approaches, and selected case reports provide hints for future research. ''Neuropsychobiology'' is a complete record of strategies and methodologies employed to study the biological basis of mental functions including their interactions with psychological and social factors.