A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents.
A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents.
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DOI：
10.1038/s41398-021-01714-y
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发表时间：
2021-11-18
影响因子：
6.8
通讯作者：
Tomoda A
中科院分区：
文献类型：
--
作者：
Nishitani S;Fujisawa TX;Hiraoka D;Makita K;Takiguchi S;Hamamura S;Yao A;Shimada K;Smith AK;Tomoda A
虐待儿童会使大脑的催产素系统失调，导致依恋模式失调。然而，如何催产素能系统在儿童谁是虐待（CM）的表观遗传影响仍然未知。我们评估了CM（n = 24）和非CM（n = 31）之间编码催产素（OXT）的基因的唾液DNA甲基化的差异，以及其对大脑结构和功能的影响，使用多模态脑成像（基于体素的形态测量，扩散张量成像，任务和静息状态功能磁共振成像）。我们发现，CM表现出更高的启动子甲基化比非CM，和9个CpG位点被观察到彼此相关，并分组为一个指数（OXTmi）。OXTmi与左侧上级顶叶（SPL）的灰质体积（GMV）呈显著负相关，与奖励任务期间的右侧壳核激活呈显著负相关，但与白色物质结构无关。使用随机森林回归模型，我们调查的敏感期和类型的虐待，贡献最大的OXTmi在CM，揭示他们是5-8岁和身体虐待（PA），分别。然而，PA（PA+）的存在是为了反映更严重的情况下，如长期暴露于多种类型的滥用，比没有PA。PA+与作为种子的右侧壳核集与左侧SPL和左侧小脑外部之间的显著更大的功能连接相关。结果表明，OXT启动子高甲基化可能导致奖励和视觉关联结构和功能的非典型发展，从而可能恶化创伤经历引起的临床方面。
Child maltreatment dysregulates the brain’s oxytocinergic system, resulting in dysfunctional attachment patterns. However, how the oxytocinergic system in children who are maltreated (CM) is epigenetically affected remains unknown. We assessed differences in salivary DNA methylation of the gene encoding oxytocin (OXT) between CM (n = 24) and non-CM (n = 31), alongside its impact on brain structures and functions using multi-modal brain imaging (voxel-based morphometry, diffusion tensor imaging, and task and resting-state functional magnetic resonance imaging). We found that CM showed higher promoter methylation than non-CM, and nine CpG sites were observed to be correlated with each other and grouped into one index (OXTmi). OXTmi was significantly negatively correlated with gray matter volume (GMV) in the left superior parietal lobule (SPL), and with right putamen activation during a rewarding task, but not with white matter structures. Using a random forest regression model, we investigated the sensitive period and type of maltreatment that contributed the most to OXTmi in CM, revealing that they were 5–8 years of age and physical abuse (PA), respectively. However, the presence of PA (PA+) was meant to reflect more severe cases, such as prolonged exposure to multiple types of abuse, than the absence of PA. PA+ was associated with significantly greater functional connectivity between the right putamen set as the seed and the left SPL and the left cerebellum exterior. The results suggest that OXT promoter hypermethylation may lead to the atypical development of reward and visual association structures and functions, thereby potentially worsening clinical aspects raised by traumatic experiences.
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DOI：
10.1073/pnas.1602809113
发表时间：
2016-07-05
影响因子：
11.1
作者：
Haas，Brian W.;Filkowski，Megan M.;Smith，Alicia K.
通讯作者：
Smith，Alicia K.
影响因子：
14.9
作者：
Coolen, Marcel W;Statham, Aaron L;Gardiner-Garden, Margaret;Clark, Susan J
通讯作者：
Clark, Susan J
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：
4.7
作者：
Mizushima SG;Fujisawa TX;Takiguchi S;Kumazaki H;Tanaka S;Tomoda A
通讯作者：
Tomoda A
影响因子：
7.6
作者：
HAZAN, C;SHAVER, P
通讯作者：
SHAVER, P