Neurobiology of Stress (Nov 2023)

Epigenetic age acceleration as a biomarker for impaired cognitive abilities in adulthood following early life adversity and psychiatric disorders

  • John M. Felt,
  • Natan Yusupov,
  • Karra D. Harrington,
  • Julia Fietz,
  • Zhenyu “Zach” Zhang,
  • Martin J. Sliwinski,
  • Nilam Ram,
  • Kieran J. O'Donnell,
  • Michael J. Meaney,
  • Frank W. Putnam,
  • Jennie G. Noll,
  • Elisabeth B. Binder,
  • Chad E. Shenk

Journal volume & issue
Vol. 27
p. 100577

Abstract

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Background: Early life adversity and psychiatric disorders are associated with earlier declines in neurocognitive abilities during adulthood. These declines may be preceded by changes in biological aging, specifically epigenetic age acceleration, providing an opportunity to uncover genome-wide biomarkers that identify individuals most likely to benefit from early screening and prevention. Methods: Five unique epigenetic age acceleration clocks derived from peripheral blood were examined in relation to latent variables of general and speeded cognitive abilities across two independent cohorts: 1) the Female Growth and Development Study (FGDS; n = 86), a 30-year prospective cohort study of substantiated child sexual abuse and non-abused controls, and 2) the Biological Classification of Mental Disorders study (BeCOME; n = 313), an adult community cohort established based on psychiatric disorders. Results: A faster pace of biological aging (DunedinPoAm) was associated with lower general cognitive abilities in both cohorts and slower speeded abilities in the BeCOME cohort. Acceleration in the Horvath clock was significantly associated with slower speeded abilities in the BeCOME cohort but not the FGDS. Acceleration in the Hannum clock and the GrimAge clock were not significantly associated with either cognitive ability. Accelerated PhenoAge was associated with slower speeded abilities in the FGDS but not the BeCOME cohort. Conclusions: The present results suggest that epigenetic age acceleration has the potential to serve as a biomarker for neurocognitive decline in adults with a history of early life adversity or psychiatric disorders. Estimates of epigenetic aging may identify adults at risk of cognitive decline that could benefit from early neurocognitive screening.

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