Davis · Translational psychiatry 2017 · longitudinal cohort study · n=46

Accelerated DNA methylation age in adolescent girls: associations with elevated diurnal cortisol and reduced hippocampal volume.

Cited 89 times in the scientific literature.

Level 3 - non-randomized controlled study

Longitudinal observational cohort study measuring biological and neuroimaging markers over time.

PubMed 28850111 · doi:10.1038/tp.2017.188 · record verified 2026-08-30

What was done

In a longitudinal study of 46 adolescent girls, researchers evaluated the associations among diurnal cortisol output, DNA methylation (DNAm) age, and hippocampal volume. Diurnal cortisol was measured as area under the curve across two daily collection periods. DNAm age was determined using established CpG site algorithms, and accelerated epigenetic age was calculated as the residual score after adjusting for chronological age. Hippocampal volumes were segmented automatically from T1-weighted structural MRI scans.

What was found

The abstract reports directional relationships without numerical statistics (such as effect sizes or p-values). Higher diurnal cortisol production was associated with accelerated DNA methylation age, which was in turn associated with reduced left hippocampal volume. Accelerated DNA methylation age significantly mediated the association between diurnal cortisol and left hippocampal volume.

Why it matters

This study provides preliminary evidence that accelerated epigenetic aging may serve as a biological link between hypothalamic-pituitary-adrenal axis dysregulation and neural structural alterations during adolescence.

Limits

The sample size is very small (n = 46) and restricted solely to adolescent girls, limiting generalizability to males and other age groups. The abstract reports no numerical effect sizes or confidence intervals. As an observational study, it cannot establish causality among cortisol, epigenetic age, and brain structure.

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