Psychological Stress During Childhood and Adolescence and Its Association With Inflammation Across the Lifespan: A Critical Review and Meta-Analysis

Psychological stress during childhood and adolescence increases risk of health problems across the lifecourse, and inflammation is implicated as an underlying mechanism. To evaluate the viability of this hypothesis, we used meta-analysis to quantify the association between childhood/adolescent stress and inflammation over the lifecourse. Furthermore, we addressed three unresolved conceptual questions: (a) Does the strength of this association change over the lifecourse? (b) Are different types of childhood/adolescent stressors differentially associated with inflammation? (c) And which components of the inflammatory response are involved? A systematic search identified 187 articles reporting 922 associations. Meta-analyses were conducted using a three-level multilevel approach and controlled for study quality, conversion confidence, and whether effect sizes were unadjusted or adjusted (n = 662, 72%). Results indicated a small but reliable overall adjusted association ( r ^ = .04). The magnitude of the association strengthened across the lifecourse-effect sizes were smallest in studies that measured inflammation in childhood ( r ^ = .02) and became progressively larger in studies of adolescence ( r ^ = .04) and adulthood ( r ^ = .05), suggesting the impact of early stress strengthens with time. By contrast, effect sizes did not vary by adversity type (socioeconomic disadvantage, maltreatment, other interpersonal stressors, and cumulative exposure across stressors), or component of inflammation (circulating biomarkers of low-grade inflammation vs. cytokine responses to microbial stimuli). Implications and future directions are discussed. Public Significance Statement Stressful experiences during the early decades of life increase susceptibility to health problems across the lifespan. Excessive inflammation is thought to be an important biological mediator of this relationship, but there has yet to be a comprehensive synthesis of the literature relevant to this hypothesis. Thus, we conducted a meta-analysis of 187 studies on the association between stress during childhood and/or adolescence and inflammation that were performed over the past 2 decades. The results indicated that inflammatory markers were higher among individuals who had experienced major psychological stress during childhood and/or adolescence. The relationship between childhood/adolescent stress and inflammatory markers increased in magnitude over the lifecourse, suggesting the influence of ea