Biological aging in childhood and adolescence following experiences of threat and deprivation: A systematic review and meta-analysis.

Abstract

Life history theory argues that exposure to early life adversity (ELA) accelerates development, although existing evidence for this varies. We present a meta-analysis and systematic review testing the hypothesis that ELA involving threat (e.g., violence exposure) will be associated with accelerated biological aging across multiple metrics, whereas exposure to deprivation (e.g., neglect, institutional rearing) and low-socioeconomic status (SES) will not. We meta-analyze 54 studies (n ϭ 116,010) examining associations of ELA with pubertal timing and cellular aging (telomere length and DNA methylation age), systematically review 25 studies (n ϭ 3,253) examining ELA and neural markers of accelerated development (cortical thickness and amygdala-prefrontal cortex functional connectivity) and evaluate whether associations of ELA with biological aging vary according to the nature of adversity experienced. ELA overall was associated with accelerated pubertal timing (d ϭ Ϫ0.10) and cellular aging (d ϭ Ϫ0.21), but these associations varied by adversity type. Moderator analysis revealed that ELA characterized by threat was associated with accelerated pubertal development (d ϭ Ϫ0.26) and accelerated cellular aging (d ϭ Ϫ0.43), but deprivation and SES were unrelated to accelerated development. Systematic review revealed associations between ELA and accelerated cortical thinning, with threatrelated ELA consistently associated with thinning in ventromedial prefrontal cortex, and deprivation and SES associated with thinning in frontoparietal, default, and visual networks. There was no consistent association of ELA with amygdala-PFC connectivity. These findings suggest specificity in the types of early environmental experiences associated with accelerated biological aging and highlight the importance of evaluating how accelerated aging contributes to health disparities and whether this process can be mitigated through early intervention. Public Significance StatementThis meta-analysis and systematic review suggests that biological aging following early life adversity, including earlier pubertal timing, advanced cellular aging, and accelerated thinning of the cortex, may be specific to children and adolescents who experienced violent or traumatic experiences early in childhood. No such effect was found for children who experienced deprivation or poverty in the absence of violence or trauma. These findings highlight a potential role of accelerated biological aging in health disparities associated with early life trauma, and a potential target for early interventions.

Prenatal stress exposure and multimodal assessment of amygdala–medial prefrontal cortex connectivity in infants

“…Previous work has documented that amygdala–mPFC functional connectivity may change differentially for those with and without early adversity exposure ( Gee et al, 2013a ; Thijssen et al, 2017 ). Yet, it is worth noting that a recent meta-analysis and review found support for the hypothesis that early adversity accelerates biological aging, but found no consistent evidence for altered amygdala–mPFC connectivity ( Colich et al, 2019 ). Several studies supported potential stress-related acceleration ( Colich et al, 2017 ; Gee et al, 2013a ; Keding and Herringa, 2016 ) and several others that indicated potential delayed development of this circuitry ( Cisler et al, 2013 ; Marusak et al, 2015 ; Silvers et al, 2017 ).…”

“…The hypothesis that stress “accelerates” the development of amygdala–mPFC circuitry is based in part on rodent research ( Callaghan and Richardson, 2011 ; Moriceau and Sullivan, 2006 ). In humans, there is some evidence that amygdala–mPFC connectivity is affected by stress experienced during childhood, yet as noted by a recent review ( Colich et al, 2019 ), approximately half of these studies indicate more positive amygdala–mPFC connectivity, whereas the other half indicate less positive connectivity in those children exposed to early adversity. In adults, alterations of this circuitry is linked to anxiety (e.g., Casey and Lee, 2015 ) and emotion regulation (e.g., Banks et al, 2007 ; Ochsner and Gross, 2005 ).…”

Multi-method assessment of pubertal timing and associations with internalizing psychopathology in early adolescent girls

“…Previous research has demonstrated that the association between ELS and pubertal timing is limited to threatrelated ELS. 41 Therefore, we excluded physical and emotional neglect from the total ELS score. To limit the ELS score to early life and before puberty, we only included items endorsed as having occurred before age 7.…”

Can Psychodynamically Oriented Early Prevention for “Children-at-Risk” in Urban Areas With High Social Problem Density Strengthen Their Developmental Potential? A Cluster Randomized Trial of Two Kindergarten-Based Prevention Programs

“…There was no consistent association of ELA with amygdala-PFC connectivity. These findings suggest specificity in the types of early environmental experiences associated with accelerated biological aging and highlight the importance of how accelerated aging contributes to health disparities and whether this process can be mitigated through early intervention” ( Colich et al, 2019 , p. 2).…”

“…It is interesting that such individualized prevention strategies increasingly receive interdisciplinary support. To mention just one example: A meta-analysis by Colich et al (2019) found that early-life adversity (ELA) involving threat (e.g., violence exposure) was associated with accelerated biological aging across multiple metrics, whereas exposure to deprivation (e.g., neglect, institutional rearing) and low socio-economic status (SES) was not. The authors meta-analyzed 46 studies ( n = 64,925) the examining association of ELA with pubertal timing and cellular aging (telomere length and DNA methylation age) in order to understand the short and long-term consequences of early-life adversities in detail and to take corrective action in an individual way.…”