Developmental Cognitive Neuroscience Lab, School of Medicine, Brain Institute of Rio Grande do Sul (InsCer), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
Laboratory of Individual Differences and Psychopathology, Pontifical Catholic University of Rio de Janeiro (PUC-Rio), Rio de Janeiro, Brazil.
Neurosci Lett. 2023 Nov 1;816:137506. doi: 10.1016/j.neulet.2023.137506. Epub 2023 Sep 29.
Substance use disorders have been associated with alterations in the oxytocinergic system, but few studies have investigated both the peptide and epigenetic mechanisms potentially implicated in the regulation of oxytocin receptor. In this study, we compared plasma oxytocin and blood DNA methylation in the OXTR gene between people with and without cocaine use disorder (CUD). We measured the oxytocin levels of 51 people with CUD during acute abstinence and of 30 healthy controls using an enzyme immunoassay. The levels of DNA methylation in four CpG sites at exon III of the OXTR gene were evaluated in a subsample using pyrosequencing. The Addiction Severity Index was used to assess clinical characteristics. We found higher oxytocin levels in men with CUD (56.5 pg/mL; 95% CI: 48.2-64.7) than in control men (33.6 pg/mL; 95% CI: 20.7-46.5), while no differences between women with and without CUD were detected. With a moderate effect size, the interaction effect between group and sex remained significant when controlling for height, weight and age data. A positive correlation in the CUD sample was found between oxytocin levels and days of psychological suffering prior to treatment enrollment. No group differences were observed regarding DNA methylation data. This suggests that CUD is associated with higher peripheral oxytocin levels in men during acute abstinence. This finding may be considered in future studies that aim at using exogenous oxytocin as a potential treatment for cocaine addiction.
物质使用障碍与催产素系统的改变有关，但很少有研究调查潜在调节催产素受体的肽和表观遗传机制。在这项研究中，我们比较了有和没有可卡因使用障碍（CUD）的人之间的血浆催产素和 OXTR 基因中的血液 DNA 甲基化。我们使用酶联免疫吸附试验测量了 51 名急性戒断期间 CUD 患者和 30 名健康对照者的催产素水平。使用焦磷酸测序评估了 OXTR 基因外显子 III 中四个 CpG 位点的 DNA 甲基化水平。使用成瘾严重程度指数评估临床特征。我们发现 CUD 男性的催产素水平较高（56.5pg/mL；95%CI：48.2-64.7），而 CUD 男性的催产素水平较高（33.6pg/mL；95%CI：20.7-46.5），而 CUD 女性之间没有差异。控制身高、体重和年龄数据后，组间和性别间的交互作用仍具有统计学意义，具有中等效应大小。在 CUD 样本中，催产素水平与治疗前心理痛苦天数之间存在正相关。关于 DNA 甲基化数据，没有观察到组间差异。这表明，在急性戒断期间，CUD 与男性外周催产素水平升高有关。这一发现可以在未来旨在使用外源性催产素作为可卡因成瘾潜在治疗方法的研究中加以考虑。
