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脑源性神经营养因子(BDNF)启动子甲基化的变化是否表明酒精复发的风险?

Do changes in the BDNF promoter methylation indicate the risk of alcohol relapse?

作者信息

Heberlein Annemarie, Büscher Patricia, Schuster Rilana, Kleimann Alexandra, Lichtinghagen Ralf, Rhein Mathias, Kornhuber Johannes, Bleich Stefan, Frieling Helge, Hillemacher Thomas

机构信息

Center for Addiction Research (CARe), Department of Psychiatry, Social Psychiatry and Psychotherapy, Medical School Hanover, Germany.

Center for Addiction Research (CARe), Department of Psychiatry, Social Psychiatry and Psychotherapy, Medical School Hanover, Germany.

出版信息

Eur Neuropsychopharmacol. 2015 Nov;25(11):1892-7. doi: 10.1016/j.euroneuro.2015.08.018. Epub 2015 Sep 5.

Abstract

The neurotrophic growth factor brain derived neurotrophic factor (BDNF) was linked to the risk of alcohol relapse in clinical studies. In this study we investigated alterations in the methylation of the BDNF gene during alcohol withdrawal (day 1, 7 and 14) in 99 male alcohol-dependent patients compared to age matched healthy males (n=33). In particular, we aimed to investigate a possible association between the BDNF promoter methylation and the self-reported duration of alcohol abstinence before relapse. Mean methylation of the BDNF promoter was significantly increased in alcohol-dependent patients compared to the healthy controls (F=10.014, p<0.001) and decreased significantly during alcohol-withdrawal (F=10.014, p<0.001). Moreover, mean methylation was associated with depressive (F=2.014, p<0.001) and anxious symptoms in the alcohol-dependent patients (F=2.228, p<0.001). On day 14 of alcohol-withdrawal we found significantly higher methylation rates in those patients who abstained longer before relapse compared to those patients who abstained shorter (F=9.938, p<0.001). Our results suggest an association between BDNF expression and the symptomatology of alcohol withdrawal and imply that changes in the methylation of the BDNF IV gene may contribute to alcohol consumption.

摘要

神经营养生长因子脑源性神经营养因子(BDNF)在临床研究中与酒精复吸风险相关。在本研究中,我们调查了99名男性酒精依赖患者在酒精戒断期间(第1天、第7天和第14天)BDNF基因甲基化的变化,并与年龄匹配的健康男性(n = 33)进行比较。具体而言,我们旨在研究BDNF启动子甲基化与复吸前自我报告的戒酒持续时间之间可能存在的关联。与健康对照组相比,酒精依赖患者中BDNF启动子的平均甲基化显著增加(F = 10.014,p < 0.001),且在酒精戒断期间显著降低(F = 10.014,p < 0.001)。此外,酒精依赖患者的平均甲基化与抑郁症状(F = 2.014, p < 0.001)和焦虑症状(F = 2.228, p < 0.001)相关。在酒精戒断第14天,我们发现与戒酒时间较短的患者相比,复吸前戒酒时间较长的患者甲基化率显著更高(F = 9.938, p < 0.001)。我们的结果表明BDNF表达与酒精戒断症状之间存在关联,并暗示BDNF IV基因甲基化的变化可能与饮酒行为有关。

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