OXTR DNA methylation moderates the developmental calibration of neural reward sensitivity.
OXTR DNA methylation moderates the developmental calibration of neural reward sensitivity.
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DOI：
10.1002/dev.22026
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发表时间：
2021-01
影响因子：
2.2
通讯作者：
Connelly JJ
中科院分区：
文献类型：
--
作者：
Gonzalez MZ;Wroblewski KL;Allen JP;Coan JA;Connelly JJ
应激反应的自适应校准模型（ACM）表明，发育经历可预测地调整生物系统以满足环境的需求。尤其重要的是奖励制度的校准。这项研究使用从青春期开始追踪的纵向样本（N = 184），模拟了早期生活压力的维度及其对催产素受体基因（OXTR）表观遗传修饰的影响以及对奖励预期的神经反应的个体差异。我们首先使用参与者 13 岁时收集的测量数据创建了一个发展背景的潜变量模型。成年后，两组参与者完成了奖励预期功能磁共振成像范式 (N = 82)，并同意对血液中两个 CpG 位点的 (OXTR) DNA 甲基化进行检测 (N = 112)。发展背景的三个潜在结构出现了：邻居的严酷、家庭的严酷、以及虐待和混乱。 CpG 位点 -924 和 -934 处的 OXTR DNA 甲基化程度较高，削弱了邻里严酷程度较高与尾状核预期奖励时神经激活增加之间的关联。在所有三个潜在结构的奖励相关区域之外也发现了交互效应。结果表明，表观遗传衍生的差异易感性模型中，高甲基化与发育环境和神经奖励预期之间的关联性降低相一致。
The Adaptive Calibration Model of Stress Responsivity (ACM) suggests that developmental experiences predictably tune biological systems to meet the demands of the environment. Particularly important is the calibration of reward systems. Using a longitudinal sample (N = 184) followed since adolescence, this study models the dimensions of early life stress and their effects on epigenetic modification of the oxytocin receptor gene (OXTR) and individual differences in neural response to reward anticipation. We first created a latent variable model of developmental context using measures collected when participants were 13 years old. As adults, two subsets of participants completed a reward anticipation fMRI paradigm (N = 82) and agreed to have their blood assayed for (OXTR) DNA methylation (N = 112) at two CpG sites. Three latent constructs of developmental context emerged: Neighborhood Harshness, Family Harshness, and Abuse and Disorder. Greater OXTR DNA methylation at CpG sites −924 and −934 blunted the association between greater Neighborhood Harshness and increased neural activation in caudate in anticipation of rewards. Interaction effects were also found outside of reward-related areas for all three latent constructs. Results indicate an epigenetically derived differential susceptibility model whereby high methylation coincides with decreased association between developmental environment and neural reward anticipation.
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影响因子：
11
作者：
Heim, C.;Young, L. J.;Nemeroff, C. B.
通讯作者：
Nemeroff, C. B.
影响因子：
4.7
作者：
Casey BJ;Cannonier T;Conley MI;Cohen AO;Barch DM;Heitzeg MM;Soules ME;Teslovich T;Dellarco DV;Garavan H;Orr CA;Wager TD;Banich MT;Speer NK;Sutherland MT;Riedel MC;Dick AS;Bjork JM;Thomas KM;Chaarani B;Mejia MH;Hagler DJ Jr;Daniela Cornejo M;Sicat CS;Harms MP;Dosenbach NUF;Rosenberg M;Earl E;Bartsch H;Watts R;Polimeni JR;Kuperman JM;Fair DA;Dale AM;ABCD Imaging Acquisition Workgroup
通讯作者：
ABCD Imaging Acquisition Workgroup
影响因子：
4.6
作者：
Gouin JP;Zhou QQ;Booij L;Boivin M;Côté SM;Hébert M;Ouellet-Morin I;Szyf M;Tremblay RE;Turecki G;Vitaro F
通讯作者：
Vitaro F
影响因子：
2
作者：
Gonzalez, Marlen Z.;Puglia, Meghan H.;Connelly, Jessica J.
通讯作者：
Connelly, Jessica J.
影响因子：
2.9
作者：
Carter, CS
通讯作者：
Carter, CS