Department of Psychiatry, Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA.
Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.
Mol Psychiatry. 2018 Apr;23(4):858-871. doi: 10.1038/mp.2017.26. Epub 2017 Mar 21.
Early adversity, in the form of abuse, neglect, socioeconomic status and other adverse experiences, is associated with poor physical and mental health outcomes. To understand the biologic mechanisms underlying these associations, studies have evaluated the relationship between early adversity and telomere length, a marker of cellular senescence. Such results have varied in regard to the size and significance of this relationship. Using meta-analytic techniques, we aimed to clarify the relationship between early adversity and telomere length while exploring factors affecting the association, including adversity type, timing and study design. A comprehensive search in July 2016 of PubMed/MEDLINE, PsycINFO and Web of Science identified 2462 studies. Multiple reviewers appraised studies for inclusion or exclusion using a priori criteria; 3.9% met inclusion criteria. Data were extracted into a structured form; the Newcastle-Ottawa Scale assessed study quality, validity and bias. Forty-one studies (N=30 773) met inclusion criteria. Early adversity and telomere length were significantly associated (Cohen's d effect size=-0.35; 95% CI, -0.46 to -0.24; P<0.0001). Sensitivity analyses revealed no outlier effects. Adversity type and timing significantly impacted the association with telomere length (P<0.0001 and P=0.0025, respectively). Subgroup and meta-regression analyses revealed that medication use, medical or psychiatric conditions, case-control vs longitudinal study design, methodological factors, age and smoking significantly affected the relationship. Comprehensive evaluations of adversity demonstrated more extensive telomere length changes. These results suggest that early adversity may have long-lasting physiological consequences contributing to disease risk and biological aging.
早期逆境,如虐待、忽视、社会经济地位和其他不良经历,与身心健康不良结果有关。为了了解这些关联的生物学机制,研究评估了早期逆境与端粒长度之间的关系,端粒长度是细胞衰老的标志物。关于这种关系的大小和意义,研究结果存在差异。使用荟萃分析技术,我们旨在澄清早期逆境与端粒长度之间的关系,同时探索影响这种关联的因素,包括逆境类型、时间和研究设计。2016 年 7 月,我们通过全面检索 PubMed/MEDLINE、PsycINFO 和 Web of Science,确定了 2462 项研究。多名评审员使用预先设定的标准评估研究的纳入或排除;3.9%的研究符合纳入标准。数据以结构化形式提取;纽卡斯尔-渥太华量表评估研究的质量、有效性和偏倚。41 项研究(N=30773)符合纳入标准。早期逆境与端粒长度呈显著相关(Cohen 的 d 效应大小=-0.35;95%CI,-0.46 至-0.24;P<0.0001)。敏感性分析显示没有异常值效应。逆境类型和时间对与端粒长度的关联有显著影响(P<0.0001 和 P=0.0025)。亚组和荟萃回归分析表明,药物使用、医疗或精神疾病、病例对照与纵向研究设计、方法学因素、年龄和吸烟显著影响这种关系。对逆境的综合评估显示出更广泛的端粒长度变化。这些结果表明,早期逆境可能对疾病风险和生物老化产生持久的生理后果。