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儿童期虐待、行为调节与学龄前儿童细胞衰老的分子标志物:一项队列研究。

Childhood maltreatment, behavioral adjustment, and molecular markers of cellular aging in preschool-aged children: A cohort study.

机构信息

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA; Bradley/Hasbro Children's Research Center, E. P. Bradley Hospital, East Providence, RI, USA.

出版信息

Psychoneuroendocrinology. 2019 Sep;107:261-269. doi: 10.1016/j.psyneuen.2019.05.015. Epub 2019 May 15.

Abstract

OBJECTIVE

Childhood maltreatment is a major risk factor for the development of behavioral problems and poor physical and mental health. Accelerated cellular aging, through reduced telomere length and mitochondrial dysfunction, may be a mechanism underlying these associations.

METHODS

Families with (n = 133) and without (n = 123) child welfare documentation of moderate-severe maltreatment in the past six months participated in this study. Children ranged in age from 3 to 5 years, were racially and ethnically diverse, and 91% qualified for public assistance. Structured record review and interviews were used to assess a history of maltreatment and other adversities. Telomere length and mitochondrial DNA copy number (mtDNAcn) were measured from saliva DNA using real-time PCR. Measures were repeated at a six-month follow-up assessment. Repeated measures general linear models were used to examine the effects of maltreatment and other adversities on telomere length and mtDNAcn over time.

RESULTS

Maltreatment and other adverse experiences were significant positive predictors of both telomere length and mtDNAcn over time. Internalizing and externalizing behavior problems were also both significantly associated with telomere length, but only internalizing symptoms were associated with mtDNAcn.

CONCLUSIONS

This is the first study to show that mtDNAcn is altered in children with stress and trauma, and the findings are consistent with recent studies of adults. Surprisingly, children who experienced moderate-severe levels of maltreatment in the prior six months had longer telomeres, possibly reflecting compensatory changes in response to recent trauma. Telomere length and mtDNAcn were also associated with behavioral problems, suggesting that these measures of cellular aging may be causally implicated in the pathophysiology of stress-related conditions.

摘要

目的

儿童期虐待是行为问题和身心健康不良发展的一个主要危险因素。通过缩短端粒长度和线粒体功能障碍导致的细胞加速老化,可能是这些关联的一种机制。

方法

本研究纳入了过去六个月内有(n=133)和无(n=123)中度至重度虐待儿童福利记录的家庭。儿童年龄在 3 至 5 岁之间,种族和民族多样,91%符合公共援助资格。使用结构化记录审查和访谈来评估虐待和其他逆境的历史。使用实时 PCR 从唾液 DNA 中测量端粒长度和线粒体 DNA 拷贝数(mtDNAcn)。在六个月的随访评估中重复进行这些测量。重复测量的一般线性模型用于检查虐待和其他逆境随时间对端粒长度和 mtDNAcn 的影响。

结果

虐待和其他不良经历是端粒长度和 mtDNAcn 随时间变化的显著正预测因子。内化和外化行为问题也与端粒长度均显著相关,但只有内化症状与 mtDNAcn 相关。

结论

这是第一项表明 mtDNAcn 在应激和创伤儿童中发生改变的研究,其发现与最近的成人研究一致。令人惊讶的是,在过去六个月中经历过中度至重度虐待的儿童的端粒更长,这可能反映了对近期创伤的补偿性变化。端粒长度和 mtDNAcn 也与行为问题相关,这表明这些细胞老化的测量可能与应激相关疾病的病理生理学有关。

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