DRD2 methylation is associated with executive control network connectivity and severity of alcohol problems among a sample of polysubstance users.
DRD2 methylation is associated with executive control network connectivity and severity of alcohol problems among a sample of polysubstance users.
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DOI：
10.1111/adb.12684
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发表时间：
2020-01
影响因子：
3.4
通讯作者：
Hutchison KE
中科院分区：
文献类型：
--
作者：
Hagerty SL;YorkWilliams SL;Bidwell LC;Weiland BJ;Sabbineni A;Blaine SK;Bryan AD;Hutchison KE
长期接触酒精和其他滥用药物与有害后果有关，包括与执行控制相关的神经网络内的功能连接缺陷。随着物质使用障碍的进展，执行控制网络(ECN)内的功能连接改变可能是逐渐无法控制酒精和其他药物消费的基础。遗传和表观遗传因素与物质使用障碍(SODS)有关。例如，多巴胺受体2(DRD2)的功能与酒精使用障碍(AUD)和相关表型有关，包括执行功能的相关因素。本研究旨在探索酒精相关问题的持续测量、DRD2基因内的表观遗传标记(甲基化)和多物质使用者样本中ECN内的功能连接性之间的关系。通过之前对多物质使用人群的研究，获得了658名受试者的社区样本，他们对酒精、尼古丁和大麻的消费跨越了使用数量和频率的范围。对静息状态的功能磁共振成像进行分析，以使用感兴趣的先验区域来识别内在连接网络。通过焦磷酸测序实现DRD2基因内功能相关位点的甲基化测量。基于回归的模型，包括中介和调节模型，测试了DRD2甲基化、内在神经网络(包括ECN)内的功能连接和酒精问题严重程度之间的关联。结果表明，DRD2平均甲基化与右侧ECN(RECN)和左侧ECN(LECN)连接性呈负相关，但与其他被测网络无关，DRD2甲基化与酒精问题的严重程度显著相关。不支持中介模型，尽管缓和模型表明RECN内边缘之间的连通性调节了DRD2甲基化和AUD严重程度之间的关系。结果支持一个理论模型，在该模型中，表观遗传因素与多物质使用者样本中酒精消费的神经生物学相关。
Chronic exposure to alcohol and other drugs of abuse has been associated with deleterious consequences, including functional connectivity deficits within neural networks associated with executive control. Altered functional connectivity within the executive control network (ECN) might underlie the progressive inability to control consumption of alcohol and other drugs as substance use disorders progress. Genetic and epigenetic factors have been associated with substance use disorders (SUDs). For example, dopamine receptor 2 (DRD2) functioning has been associated with alcohol use disorder (AUD) and related phenotypes, including correlates of executive functioning. The present study aims to explore the relationship between a continuous measure of alcohol-related problems, epigenetic markers (methylation) within the DRD2 gene, and functional connectivity within the ECN among a sample of polysubstance users. A community sample of 658 subjects, whose consumption of alcohol, nicotine, and cannabis span across a spectrum of quantity and frequency of use, were obtained across previous studies in polysubstance using populations. Resting state functional magnetic resonance imaging was analyzed to identify intrinsic connectivity networks using a priori regions of interest. Methylation measurement of functionally relevant sites within the DRD2 gene was achieved via pyrosequencing. Regression-based models, including mediation and moderation models, tested the association between DRD2 methylation, functional connectivity within intrinsic neural networks (including the ECN), and severity of alcohol problems. Results suggest that average DRD2 methylation was negatively associated with right ECN (RECN) and left ECN (LECN) connectivity, but not associated with other networks tested, and DRD2 methylation was significantly associated with alcohol problems severity. Mediation models were not supported, although moderation models suggested that connectivity between edges within the RECN moderated the relationship between DRD2 methylation and AUD severity. Results support a theoretical model in which epigenetic factors are associated with neurobiological correlates of alcohol consumption among a sample of polysubstance users.
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影响因子：
64.5
作者：
Goldberg, Aaron D.;Allis, C. David;Bernstein, Emily
通讯作者：
Bernstein, Emily
影响因子：
2.5
作者：
Gonzalez-Burgos, G;Kroener, S;Barrionuevo, G
通讯作者：
Barrionuevo, G
DOI：
10.1177/1073858414525995
发表时间：
2014-12
期刊：
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子：
--
作者：
Cole MW;Repovš G;Anticevic A
通讯作者：
Anticevic A
影响因子：
1.2
作者：
Heisler, Jillian M.;Morales, Juan;O'Connor, Jason C.
通讯作者：
O'Connor, Jason C.
影响因子：
3.4
作者：
Courtney KE;Ghahremani DG;Ray LA
通讯作者：
Ray LA