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Childhood adversity, accelerated GrimAge, and associated health consequences

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Abstract

Childhood adversity is linked to psychological, behavioral, and physical health problems, including obesity and cardiometabolic disease. Epigenetic alterations are one pathway through which the effects of early life stress and adversity might persist into adulthood. Epigenetic mechanisms have also been proposed to explain why cardiometabolic health can vary greatly between individuals with similar Body Mass Index (BMIs). We evaluated two independent cross-sectional cohorts of adults without known medical illness, one of which explicitly recruited individuals with early life stress (ELS) and control participants (n = 195), and the other a general community sample (n = 477). In these cohorts, we examine associations between childhood adversity, epigenetic aging, and metabolic health. Childhood adversity was associated with increased GrimAge Acceleration (GAA) in both cohorts, both utilizing a dichotomous yes/no classification (both p < 0.01) as well as a continuous measure using the Childhood Trauma Questionnaire (CTQ) (both p < 0.05). Further investigation demonstrated that CTQ subscales for physical and sexual abuse (both p < 0.05) were associated with increased GAA in both cohorts, whereas physical and emotional neglect were not. In both cohorts, higher CTQ was also associated with higher BMI and increased insulin resistance (both p < 0.05). Finally, we demonstrate a moderating effect of BMI on the relationship between GAA and insulin resistance where GAA correlated with insulin resistance specifically at higher BMIs. These results, which were largely replicated between two independent cohorts, suggest that interactions between epigenetics, obesity, and metabolic health may be important mechanisms through which childhood adversity contributes to long-term physical and metabolic health effects.

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Acknowledgements

We would like to acknowledge the study participants, the many research staff who helped to collect the data, Asi Polly Gobin for data management, and the Yale Center for Genome Analysis for DNA methylation profiling.

Funding

This research was supported by National Institutes of Health grants MH101107 (ART), UL1-DE019586 (RS), PL1-DA24859 (RS), R01-AA013892 (RS), NIH R01DA047063 (KX), NIH T32MH019961 (ZMH), and NIH R25MH071584 (ZMH). Z.M.H. is also supported by the Yale Physician Scientist Development Award and CTSA (NIH UL1 TR001863). Dr. Tyrka’s time was additionally supported by P20GM139767 and R01HD086487 (ART). Dr. Daniels received support from MH101076 (ART) and HD101392 (ART). Dr. Kudinova’s time was supported by NIMH (K23MH122587) and NIGMS Bradley Hospital COBRE Center (P20GM139743). Dr. Brick received support from NIDA (R01DA054116).

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Author notes

  1. Rajita Sinha and Audrey Tyrka have contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, Yale University, New Haven, CT, USA

    Zachary M. Harvanek, Ke Xu & Rajita Sinha

  2. Yale Stress Center, Yale University, New Haven, CT, USA

    Zachary M. Harvanek & Rajita Sinha

  3. Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA

    Anastacia Y. Kudinova, Leslie Brick, Teresa E. Daniels & Audrey R. Tyrka

  4. Bradley Hospital, Providence, RI, USA

    Anastacia Y. Kudinova & Teresa E. Daniels

  5. New York University Grossman School of Medicine, New York, USA

    Samantha A. Wong

  6. Department of Psychiatry, Connecticut Veteran Healthcare System, West Haven, CT, USA

    Ke Xu

  7. Initiative for Stress, Trauma, and Resilience, Alpert Medical School of Brown University, Providence, RI, USA

    Teresa E. Daniels & Audrey R. Tyrka

  8. Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA

    Teresa E. Daniels & Audrey R. Tyrka

  9. Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    Carmen Marsit & Amber Burt

  10. Department of Neuroscience, Yale University, New Haven, CT, USA

    Rajita Sinha

  11. Child Study Center, Yale University, New Haven, CT, USA

    Rajita Sinha

Authors
  1. Zachary M. Harvanek
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  2. Anastacia Y. Kudinova
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  4. Ke Xu
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  9. Rajita Sinha
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  10. Audrey R. Tyrka
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Correspondence to Zachary M. Harvanek.

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Harvanek, Z.M., Kudinova, A.Y., Wong, S.A. et al. Childhood adversity, accelerated GrimAge, and associated health consequences. J Behav Med (2024). https://doi.org/10.1007/s10865-024-00496-0

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