Early life adversity and telomere length: a meta-analysis

Abstract

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.

Figure 1. PRISMA flow diagram of included studies

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram for identification and inclusion of studies in the meta-analysis.

Figure 2. Forest plot of early life adversity and telomere length

Forest plot of effect sizes reported as Cohen’s d (x-axis) evaluating early life adversity and telomere length using the random effects model. Points represent effect size; lines represent 95% confidence intervals (CI). Diamond indicates overall effect size and 95% CI.

Figure 3. Subgroup moderator analyses

Subgroup analyses. Sub-group analyses were conducted using a continuous random effects model. Black squares represent the Cohen’s d effect size and lines represent 95% confidence interval (CI). A. Subgroup analysis by type of adversity exposure. B. Subgroup analysis by medical conditions, psychiatric disorders, and medication use. C. Subgroup analysis by study techniques. k = number of studies per group, N = total number of subjects from all studies; SES = socioeconomic status; qPCR = quantitative polymerase chain reaction.

Figure 4. Meta-regression analyses

Meta-regression of early life adversity timing and telomere length. Each circle represents a study with size proportional to that study’s weight in the analysis. A. Developmental stage at age of adversity exposure versus Cohen’s d. Studies were grouped according to the reported age of adversity assessment. k = 7 studies assessed adversity during early development (prenatal-4 years), k = 10 during childhood (up to 12 years), and k = 23 during adolescence (up to 18 years). No studies are represented in more than one category. B. Years since adversity exposure versus Cohen’s d. X-axis values represent mean study population age minus the oldest age of reported adversity exposure.