Early Adversity Imprints Multisystem Biological Aging: A Longitudinal Study of Adversity Dimensions and Aging...

Early-life stress (ELS) is associated with accelerated biological aging; however, it is unclear whether dimensions of adversity such as threat and deprivation produce distinct multisystem aging phenotypes. Here we characterize, for the first time, the multivariate copatterning of stress dimensions and aging biomarkers and examine whether such phenotypes predict psychopathology 6 years later.

In a longitudinal sample (N = 225; ages 9-13; 58.7% female) studied across 4 waves (approximately 6 years), 16 measures of stress exposure were reduced via principal component analysis to 3 orthogonal dimensions: cumulative stress & trauma, low parental support, and neighborhood disadvantage. Canonical correlation analysis (CCA) related these dimensions to baseline levels and developmental trajectories of 6 aging biomarkers (mitochondrial DNA [mtDNA], telomere length, cortisol, body mass index [BMI], pubertal stage, and brain age gap). Canonical variate (CV) scores predicted internalizing, externalizing, and total problems in late adolescence (n = 142).

CCA identified 2 significant CVs at baseline. CV1 linked deprivation-related stress (low parental support/neighborhood disadvantage) to a cellular-metabolic aging profile (higher BMI, older brain age, and lower mtDNA) (r = 0.39, p < .001). CV2 linked cumulative stress and trauma to a threat-responsive neuroendocrine maturation profile (earlier pubertal stage, higher cortisol, higher BMI, and higher mtDNA) (r = 0.24, p = .003). ELS was not associated with biomarker trajectories (ps > .20), consistent with early embedding. Only the threat phenotype (CV2) predicted psychopathology (β = 6.98, p = .004, R ² = 0.12).

ELS is biologically embedded along adversity type-specific pathways detectable by late childhood, supporting a developmental imprinting model. A threat-related multisystem aging phenotype conferred transdiagnostic psychiatric risk in late adolescence, pointing to pre-adolescent development as an important window for prevention.